The effects of a priming dose of alcohol and drinking environment on snack food intake.

PubMed

Rose, A K; Hardman, C A; Christiansen, P

2015-12-01

Alcohol consumption is a potential risk factor for being overweight. We aimed to investigate the effects of an alcohol priming dose and an alcohol-related environment on snacking behaviour. One hundred and fourteen social drinkers completed one of four experimental sessions either receiving a priming dose of alcohol (.6 g/kg) or soft drink in a bar-lab or a sterile lab. Participants provided ratings of appetite, snack urge, and alcohol urge before and after consuming their drinks. Participants completed an ad libitum snack taste test of savoury and sweet, healthy and unhealthy foods before completing the self-reports a final time. Appetite and snack urge increased more following alcohol consumption, and decreased to a lesser extent following the taste test relative to the soft drink. Total calories (including drink calories) consumed were significantly higher in the alcohol groups. There was a marginal effect of environment; those in the bar-lab consumed a higher proportion of unhealthy foods. These effects were more pronounced in those who were disinhibited. While alcohol may not increase food consumption per se, alcohol may acutely disrupt appetite signals, perhaps via processes of reward and inhibitory control, resulting in overall greater calorie intake. Individuals who are generally disinhibited may be more vulnerable to the effects of alcohol and drinking environments on eating behaviour. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of alcohol mixed with energy drink and alcohol alone on subjective intoxication.

PubMed

Ulbrich, Andrea; Hemberger, Sophie Helene; Loidl, Alexandra; Dufek, Stephanie; Pablik, Eleonore; Fodor, Sugarka; Herle, Marion; Aufricht, Christoph

2013-12-01

Recent studies suggest that the combination of caffeine-containing drinks together with alcohol might reduce the subjective feelings of alcohol intoxication-the so-called "masking effect". In this study, we aimed to review the effects of alcohol in combination with caffeine or energy drink with special focus on the "masking effect". Fifty-two healthy male volunteers were analysed concerning breath alcohol concentration and subjective sensations of intoxication using a 18 item Visual Analogue Scale in a randomised, double-blinded, controlled, four treatments cross-over trial after consumption of (A) placebo, (B) alcohol (vodka 37.5% at a dose of 46.5 g ethanol), (C) alcohol in combination with caffeine at a dose of 80 mg (equivalent to one 250 ml can of energy drink) and (D) alcohol in combination with energy drink at a dose of 250 ml (one can). Primary variables were headache, weakness, salivation and motor coordination. Out of four primary variables, weakness and motor coordination showed a statistically significant difference between alcohol and non-alcohol group, out of 14 secondary variables, five more variables (dizziness, alterations in sight, alterations in walking, agitation and alterations in speech) also showed significant differences due mainly to contrasts with the non-alcohol group. In none of these end points, could a statistically significant effect be found for the additional ingestion of energy drink or caffeine on the subjective feelings of alcohol intoxication. This within-subjects study does not confirm the presence of a "masking effect" when combining caffeine or energy drink with alcohol.

Effect of memantine on cue-induced alcohol craving in recovering alcohol-dependent patients.

PubMed

Krupitsky, Evgeny M; Neznanova, Olga; Masalov, Dimitry; Burakov, Andrey M; Didenko, Tatyana; Romanova, Tatyana; Tsoy, Marina; Bespalov, Anton; Slavina, Tatyana Y; Grinenko, Alexander A; Petrakis, Ismene L; Pittman, Brian; Gueorguieva, Ralitza; Zvartau, Edwin E; Krystal, John H

2007-03-01

Ethanol blocks N-methyl-d-aspartic acid (NMDA) glutamate receptors. Increased NMDA receptor function may contribute to motivational disturbances that contribute to alcoholism. The authors assessed whether the NMDA receptor antagonist memantine reduces cue-induced alcohol craving and produces ethanol-like subjective effects. Thirty-eight alcohol-dependent inpatients participated in three daylong testing sessions in a randomized order under double-blind conditions. On each test day, subjects received 20 mg of memantine, 40 mg of memantine, or placebo, and subjective responses to treatment were assessed. The level of alcohol craving was assessed before and after exposure to an alcohol cue. Memantine did not stimulate alcohol craving before exposure to an alcohol cue, and it attenuated alcohol cue-induced craving in a dose-related fashion. It produced dose-related ethanol-like effects without adverse cognitive or behavioral effects. These data support further exploration of whether well-tolerated NMDA receptor antagonists might have a role in the treatment of alcoholism.

Effects of Age and Acute Moderate Alcohol Administration on Electrophysiological Correlates of Working Memory Maintenance

PubMed Central

Boissoneault, Jeff; Frazier, Ian; Lewis, Ben; Nixon, Sara Jo

2016-01-01

Background Previous studies suggest older adults may be differentially susceptible to the acute neurobehavioral effects of moderate alcohol intake. To our knowledge, no studies have addressed acute moderate alcohol effects on the electrophysiological correlates of working memory in younger and older social drinkers. This study characterized alcohol-related effects on frontal theta (FTP) and posterior alpha power (PAP) associated with maintenance of visual information during a working memory task. Methods Older (55–70 years of age; n = 51, 29 women) and younger (25–35 years of age; n = 70, 39 women) community-dwelling moderate drinkers were recruited for this study. Participants were given either placebo or an active dose targeting breath alcohol concentrations (BrACs) of 0.04 or 0.065 g/dL. Following absorption, participants completed a visual working memory task assessing cue recognition following a 9s delay. FTP and PAP were determined via Fourier transformation and subjected to 2 (age group) X 3 (dose) X 2 (repeated: working memory task condition) mixed models analysis. Results In addition to expected age-related reductions in PAP, a significant age group X dose interaction was detected for PAP such that 0.04 g/dL dose level was associated with greater PAP in younger adults but lower PAP in their older counterparts. PAP was lower in older vs younger adults at both active doses. Further mixed models revealed a significant negative association between PAP and working memory efficiency for older adults. No effects of age, dose, or their interaction were noted for FTP. Conclusions Results bolster the small but growing body of evidence that older adults exhibit differential sensitivity to the neurobehavioral effects of moderate alcohol use. Given the theoretical role of PAP in attentional and working memory function, these findings shed light on the attentional mechanisms underlying effects of acute moderate alcohol on working memory efficiency in older adults. PMID:27419803

Low doses of alcohol potentiate GABA sub B inhibition of spontaneous activity of hippocampal CA1 neurons in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Criado, J.R.; Thies, R.

1991-03-11

Low doses of alcohol facilitate firing of hippocampal neurons. Such doses also enhance the inhibitory actions of GABA. Alcohol is known to potentiate inhibition via GABA{sub A} receptors. However, the effects of alcohol on GABA{sub B} receptor function are not understood. Spontaneous activity of single units was recorded from CA1 neurons of male rats anesthetized with 1.0% halothane. Electrical recordings and local application of drugs were done with multi-barrel pipettes. CA1 pyramidal neurons fired spontaneous bursts of action potentials. Acute alcohol decreased the interval between bursts, a mild excitatory action. Alcohol also more than doubled the period of complete inhibitionmore » produced by local application of both GABA and baclofen. These data suggest that GABA{sub B}-mediated inhibition is also potentiated by low doses of alcohol.« less

The effects of alcohol on the recognition of facial expressions and microexpressions of emotion: enhanced recognition of disgust and contempt.

PubMed

Felisberti, Fatima; Terry, Philip

2015-09-01

The study compared alcohol's effects on the recognition of briefly displayed facial expressions of emotion (so-called microexpressions) with expressions presented for a longer period. Using a repeated-measures design, we tested 18 participants three times (counterbalanced), after (i) a placebo drink, (ii) a low-to-moderate dose of alcohol (0.17 g/kg women; 0.20 g/kg men) and (iii) a moderate-to-high dose of alcohol (0.52 g/kg women; 0.60 g/kg men). On each session, participants were presented with stimuli representing six emotions (happiness, sadness, anger, fear, disgust and contempt) overlaid on a generic avatar in a six-alternative forced-choice paradigm. A neutral expression (1 s) preceded and followed a target expression presented for 200 ms (microexpressions) or 400 ms. Participants mouse clicked the correct answer. The recognition of disgust was significantly better after the high dose of alcohol than after the low dose or placebo drinks at both durations of stimulus presentation. A similar profile of effects was found for the recognition of contempt. There were no effects on response latencies. Alcohol can increase sensitivity to expressions of disgust and contempt. Such effects are not dependent on stimulus duration up to 400 ms and may reflect contextual modulation of alcohol's effects on emotion recognition. Copyright © 2015 John Wiley & Sons, Ltd.

Effects of Age and Acute Moderate Alcohol Administration on Electrophysiological Correlates of Working Memory Maintenance.

PubMed

Boissoneault, Jeff; Frazier, Ian; Lewis, Ben; Nixon, Sara Jo

2016-09-01

Previous studies suggest older adults may be differentially susceptible to the acute neurobehavioral effects of moderate alcohol intake. To our knowledge, no studies have addressed acute moderate alcohol effects on the electrophysiological correlates of working memory in younger and older social drinkers. This study characterized alcohol-related effects on frontal theta (FTP) and posterior alpha power (PAP) associated with maintenance of visual information during a working memory task. Older (55 to 70 years of age; n = 51, 29 women) and younger (25 to 35 years of age; n = 70, 39 women) community-dwelling moderate drinkers were recruited for this study. Participants were given either placebo or an active dose targeting breath alcohol concentrations (BrACs) of 0.04 or 0.065 g/dl. Following absorption, participants completed a visual working memory task assessing cue recognition following a 9-s delay. FTP and PAP were determined via Fourier transformation and subjected to 2 (age group) × 3 (dose) × 2 (repeated: working memory task condition) mixed models analysis. In addition to expected age-related reductions in PAP, a significant age group × dose interaction was detected for PAP such that 0.04 g/dl dose level was associated with greater PAP in younger adults but lower PAP in their older counterparts. PAP was lower in older versus younger adults at both active doses. Further mixed models revealed a significant negative association between PAP and working memory efficiency for older adults. No effects of age, dose, or their interaction were noted for FTP. Results bolster the small but growing body of evidence that older adults exhibit differential sensitivity to the neurobehavioral effects of moderate alcohol use. Given the theoretical role of PAP in attentional and working memory function, these findings shed light on the attentional mechanisms underlying effects of acute moderate alcohol on working memory efficiency in older adults. Copyright © 2016 by the Research Society on Alcoholism.

Acute alcohol administration improves skilled reaching success in intact but not 6-OHDA dopamine depleted rats: a subsystems analysis of the motoric and anxiolytic effects of alcohol.

PubMed

Metz, Gerlinde A; Gonzalez, Claudia L R; Piecharka, Dionne M; Whishaw, Ian Q

2003-06-16

Low doses of alcohol impair movement and reduce anxiety. Most assessments of movement under ethyl alcohol (alcohol) in the rat have been tests of whole body movements, however. There has been no examination of the effects of alcohol on skilled limb movements, such as reaching for food with a forelimb. This was the purpose of the present study. Rats were trained to reach through a slot of a box with a forelimb in order to obtain a food pellet located on an external shelf. Once asymptotic performance was achieved, rats were given alcohol (20 ml of 8, 12 or 20% (v/v) solution) in separate tests to establish a relationship between alcohol ingestion and skilled reaching performance. Acute treatment with all doses of alcohol impaired postural support, but doses of 8 and 12% alcohol improved skilled reaching success. Qualitative analysis of the movements used for reaching at doses of 8 and 12% indicated that some limb components of the reaching movement were also impaired, perhaps secondarily due to impaired posture. In contrast, the reaching success of rats with unilateral dopamine depletion, induced with the neurotoxin 6-hydroxydopamine (6-OHDA) in the nigrostriatal bundle, was impaired by the same dose of alcohol that improved reaching success in control rats. The finding of improved success in reaching associated with reduced postural support in normal rats suggests a differential action of alcohol on movement subsystems underlying posture relative to skilled movement that depends upon an intact dopaminergic system. The results are also discussed with respect to the relationship of subsystems of movement and anxiety.

Effects of alcohol on body-sway patterns in human subjects.

PubMed

Nieschalk, M; Ortmann, C; West, A; Schmäl, F; Stoll, W; Fechner, G

1999-01-01

The vestibulospinal aspects of vestibular function are commonly neglected in the evaluation of alcohol-induced intoxication. Thus, in the present study the effect of an acute intoxication with a low or moderate quantity of alcohol was examined with respect to the equilibrium in 30 healthy subjects. The blood alcohol concentration (BAC) was measured 30 min after the ingestion of the last alcohol, ranging between 0.22 and 1.59 per thousand. Stability of stance was quantified by static platform posturography in Romberg-test conditions with eyes open and eyes closed. Among other parameters, the average body sway path (SP) and area of body sway (SA) were assessed. Posturography revealed a significant increase in body sway. There was a positive correlation between SA (or SP) and BAC both with eyes open and eyes closed. Multiple group comparisons revealed that the large-alcohol-dose group (BAC > or = 1.0 per thousand) could be clearly differentiated from test cases with BAC lower than 0.8 per thousand. Sway area was the most sensitive parameter for detecting increased body sway after alcohol ingestion. The area increase, present not only with eyes closed but with eyes open, revealed an inadequate compensation of the ethanol-induced ataxia by visual stabilization. The Romberg's quotient, which denotes eyes closed relative to eyes open, remained constant. The increase in sway path with eyes closed showed an omnidirectional sway. A comparison of the sway pattern of subjects after acute ethanol ingestion with the data of patients with permanent cerebellar lesions suggested that the acute effect of alcohol resembles that of a lesion of the spinocerebellum. This finding contrasts with earlier studies, which postulated an acute effect of ethanol resembling that in patients with an atrophy of the anterior lobe of the cerebellum due to chronic alcohol abuse. In seven cases of the lower dose group (BAC < or = 0.8 per thousand), a reduction in body sway after alcohol ingestion was observed. This finding may be consistent with a dose-related biphasic action of alcohol, which - besides its well-known depressant effects with high doses - also shows stimulatory action with small doses.

Dose-Related Effects of Alcohol on Cognitive Functioning

PubMed Central

Dry, Matthew J.; Burns, Nicholas R.; Nettelbeck, Ted; Farquharson, Aaron L.; White, Jason M.

2012-01-01

We assessed the suitability of six applied tests of cognitive functioning to provide a single marker for dose-related alcohol intoxication. Numerous studies have demonstrated that alcohol has a deleterious effect on specific areas of cognitive processing but few have compared the effects of alcohol across a wide range of different cognitive processes. Adult participants (N = 56, 32 males, 24 females aged 18–45 years) were randomized to control or alcohol treatments within a mixed design experiment involving multiple-dosages at approximately one hour intervals (attained mean blood alcohol concentrations (BACs) of 0.00, 0.048, 0.082 and 0.10%), employing a battery of six psychometric tests; the Useful Field of View test (UFOV; processing speed together with directed attention); the Self-Ordered Pointing Task (SOPT; working memory); Inspection Time (IT; speed of processing independent from motor responding); the Traveling Salesperson Problem (TSP; strategic optimization); the Sustained Attention to Response Task (SART; vigilance, response inhibition and psychomotor function); and the Trail-Making Test (TMT; cognitive flexibility and psychomotor function). Results demonstrated that impairment is not uniform across different domains of cognitive processing and that both the size of the alcohol effect and the magnitude of effect change across different dose levels are quantitatively different for different cognitive processes. Only IT met the criteria for a marker for wide-spread application: reliable dose-related decline in a basic process as a function of rising BAC level and easy to use non-invasive task properties. PMID:23209840

Protective effect of heat-treated cucumber (Cucumis sativus L.) juice on alcohol detoxification in experimental rats.

PubMed

Bajpai, Vivek K; Kim, Na-Hyung; Kim, Ji-Eun; Kim, Kangmin; Kang, Sun Chul

2016-05-01

In this study, heat-treated cucumber juice was assessed for its protective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats. Initially, during detoxification of alcohol, all groups were orally dosed to 22% alcohol (6ml/kg body weight) along with different concentrations of heat-treated cucumber juice (10, 100 and 500mg/kg) and commercial goods for hangover-removal on sale (2ml/kg). Cucumber juice was dosed before 30 min, and simultaneously after 30min of alcohol administration, and its hepatoprotective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats was evaluated. As a result, after 7h, remarkable reduction was found in the blood alcohol levels for all concentrations of cucumber juice treatment. Treatment with cucumber juice resulted in increasing dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) enzymatic activities in rat liver at 9h after alcohol administration thereby stimulated blood alcohol metabolism as compared with control group. The effect of heat-treated cucumber juice on alcohol detoxification was observed only in the rats treated before 30min from alcohol administration. These findings indicate that heat-treated cucumber juice has significant protective effect on alcohol detoxification in experimental rats, suggesting its usefulness in the treatment of liver injury caused by alcohol consumption.

Pharmacologic dissociation between impulsivity and alcohol drinking in High Alcohol Preferring mice

PubMed Central

Oberlin, Brandon G.; Bristow, R. Evan; Heighton, Meredith E.; Grahame, Nicholas J.

2014-01-01

Background Impulsivity is genetically correlated with, and precedes addictive behaviors and alcoholism. If impulsivity or attention is causally related to addiction, certain pharmacological manipulations of impulsivity and/or attention may affect alcohol drinking, and vice versa. The current studies were designed to explore the relationship among impulsivity, drinking, and vigilance in selectively bred High Alcohol Preferring (HAP) mice, a line that has previously demonstrated both high impulsivity and high alcohol consumption. Amphetamine, naltrexone and memantine were tested in a delay discounting (DD) task for their effects on impulsivity and vigilance. The same drugs and doses were also assessed for effects on alcohol drinking in a two-bottle choice test. Methods HAP mice were subjected to a modified version of adjusting amount DD using 0.5 sec and 10 sec delays to detect decreases and increases, respectively, in impulsive responding. In 2 experiments, mice were given amphetamine (0.4, 0.8 or 1.2 mg/kg), naltrexone (3 and 10 mg/kg), and memantine (1 and 5 mg/kg) before DD testing. Another pair of studies used scheduled access, two-bottle choice drinking to assess effects of amphetamine (0.4, 1.2, or 3.0 mg/kg), naltrexone (3 and 10 mg/kg), and memantine (1 and 5 mg/kg) on alcohol consumption. Results Amphetamine dose-dependently reduced impulsivity and vigilance decrement in DD, but similar doses left alcohol drinking unaffected. Naltrexone and memantine decreased alcohol intake at doses that did not affect water drinking, but had no effects on impulsivity or vigilance decrement in the DD task. Conclusions Contrary to our hypothesis, none of the drugs tested here, while effective either on alcohol drinking or impulsivity, decreased both behaviors. These findings suggest that the genetic association between drinking and impulsivity observed in this population is mediated by mechanisms other than those targeted by the drugs tested in these studies. PMID:20491739

Controlled vaporized cannabis, with and without alcohol: subjective effects and oral fluid-blood cannabinoid relationships.

PubMed

Hartman, Rebecca L; Brown, Timothy L; Milavetz, Gary; Spurgin, Andrew; Gorelick, David A; Gaffney, Gary; Huestis, Marilyn A

2016-07-01

Vaporized cannabis and concurrent cannabis and alcohol intake are commonplace. We evaluated the subjective effects of cannabis, with and without alcohol, relative to blood and oral fluid (OF, advantageous for cannabis exposure screening) cannabinoid concentrations and OF/blood and OF/plasma vaporized-cannabinoid relationships. Healthy adult occasional-to-moderate cannabis smokers received a vaporized placebo or active cannabis (2.9% and 6.7% Δ(9) -tetrahydrocannabinol, THC) with or without oral low-dose alcohol (~0.065g/210L peak breath alcohol concentration [BrAC]) in a within-subjects design. Blood and OF were collected up to 8.3 h post-dose and subjective effects measured at matched time points with visual-analogue scales and 5-point Likert scales. Linear mixed models evaluated subjective effects by THC concentration, BrAC, and interactions. Effects by time point were evaluated by dose-wise analysis of variance (ANOVA). OF versus blood or plasma cannabinoid ratios and correlations were evaluated in paired-positive specimens. Nineteen participants (13 men) completed the study. Blood THC concentration or BrAC significantly associated with subjective effects including 'high', while OF contamination prevented significant OF concentration associations <1.4 h post-dose. Subjective effects persisted through 3.3-4.3 h, with alcohol potentiating the duration of the cannabis effects. Effect-versus-THC concentration and effect-versus-alcohol concentration hystereses were counterclockwise and clockwise, respectively. OF/blood and OF/plasma THC significantly correlated (all Spearman r≥0.71), but variability was high. Vaporized cannabis subjective effects were similar to those previously reported after smoking, with duration extended by concurrent alcohol. Cannabis intake was identified by OF testing, but OF concentration variability limited interpretation. Blood THC concentrations were more consistent across subjects and more accurate at predicting cannabis' subjective effects. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Differential residual effects of zaleplon and zopiclone on actual driving: a comparison with a low dose of alcohol.

PubMed

Vermeeren, Annemiek; Riedel, Wim J; van Boxtel, Martin P J; Darwish, Mona; Paty, Isabelle; Patat, Alain

2002-03-15

To compare residual effects of zaleplon 10 mg, zopiclone 7.5 mg, and placebo, and a social dose of alcohol on car driving, memory, and psychomotor performance. Two-part placebo controlled, crossover study. Part 1 was single blind, Part 2 double blind. University research institute. Thirty healthy volunteers (15 men and 15 women, mean age 32 +/- 7 years) In Part 1 alcohol and alcohol-placebo drinks were administered around noon. In Part 2 single oral doses of zaleplon 10 mg, zopiclone 7.5 mg and placebo were administered at bedtime. A highway driving test, laboratory tests of word learning, critical tracking and divided attention, and subjective assessments of sleep, mood, and effects of treatments on driving. Driving started 40 minutes after a second alcohol dose in Part 1, and 10 hours after drug intake in Part 2. The results demonstrated that alcohol, at average plasma concentrations of approximately 0.030 g/dl, significantly impaired performance in all tests. Zaleplon's residual effects did not differ significantly from those of placebo in any test. In contrast, zopiclone had significant residual effects on driving, divided attention, and memory. The magnitude of impairment in the driving test observed the morning after zopiclone 7.5 mg was twice that observed with alcohol. Zaleplon 10 mg has no residual effects on driving when taken at bedtime, 10 hours before driving. In contrast, zopiclone 7.5 mg can cause marked residual impairment. Patients should be advised to avoid driving the morning after zopiclone administration.

Low doses of alcohol substantially decrease glucose metabolism in the human brain.

PubMed

Volkow, Nora D; Wang, Gene-Jack; Franceschi, Dinko; Fowler, Joanna S; Thanos, Panayotis Peter K; Maynard, Laurence; Gatley, S John; Wong, Christopher; Veech, Richard L; Kunos, George; Kai Li, Ting

2006-01-01

Moderate doses of alcohol decrease glucose metabolism in the human brain, which has been interpreted to reflect alcohol-induced decreases in brain activity. Here, we measure the effects of two relatively low doses of alcohol (0.25 g/kg and 0.5 g/kg, or 5 to 10 mM in total body H2O) on glucose metabolism in the human brain. Twenty healthy control subjects were tested using positron emission tomography (PET) and FDG after placebo and after acute oral administration of either 0.25 g/kg, or 0.5 g/kg of alcohol, administered over 40 min. Both doses of alcohol significantly decreased whole-brain glucose metabolism (10% and 23% respectively). The responses differed between doses; whereas the 0.25 g/kg dose predominantly reduced metabolism in cortical regions, the 0.5 g/kg dose reduced metabolism in cortical as well as subcortical regions (i.e. cerebellum, mesencephalon, basal ganglia and thalamus). These doses of alcohol did not significantly change the scores in cognitive performance, which contrasts with our previous results showing that a 13% reduction in brain metabolism by lorazepam was associated with significant impairment in performance on the same battery of cognitive tests. This seemingly paradoxical finding raises the possibility that the large brain metabolic decrements during alcohol intoxication could reflect a shift in the substrate for energy utilization, particularly in light of new evidence that blood-borne acetate, which is markedly increased during intoxication, is a substrate for energy production by the brain.

Combined use of alcohol and energy drinks: Dose relationship with self-reported physiological stimulation and sedation side effects.

PubMed

Droste, Nicolas; Peacock, Amy; Bruno, Raimondo; Pennay, Amy; Zinkiewicz, Lucy; Lubman, Dan I; Miller, Peter

2017-08-01

Negative physiological stimulation and sedation side effects are experienced by a significant proportion of consumers who consume alcohol mixed with energy drinks (AmED). Few studies have compared the frequency of side effects between sessions of AmED and sessions of alcohol only within-subject, and none have explored a dose relationship. Explore the occurrence of self-reported physiological stimulant and sedative side effects between sessions of AmED and alcohol only, and at varying ED dosage levels within AmED sessions. A convenience sample of 2953 residents of New South Wales, Australia completed an online survey. N=731 AmED users reported daily caffeine intake, typical alcohol and AmED consumption, and past 12-month experience of physiological stimulation and sedation side effects during AmED and alcohol only sessions. Within-subject analyses compared occurrence of side effects between session types. Hierarchical binary logistic regression analyses explored the association of ED dose during AmED sessions with the experience of physiological side effects. There were greater odds of most stimulant side effects, and lower odds of sedation side effects, during AmED sessions compared to alcohol only sessions. Compared to one ED, consumption of three or more EDs was significantly associated with the majority of both stimulant and alcohol intoxication side effects after controlling for demographics and consumption covariates. AmED is associated with perceived changes in physiological stimulant and sedation side effects of alcohol. Experience of side effects is positively associated with ED dosage. Future research should account for varying ED dosage, and reflect real world consumption levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nicotine Interactions with Low-Dose Alcohol: Pharmacological Influences on Smoking and Drinking Motivation

PubMed Central

Oliver, Jason A.; Blank, Melissa D.; Rensburg, Kate Janse Van; MacQueen, David A.; Brandon, Thomas H.; Drobes, David J.

2014-01-01

An extensive literature documents a close association between cigarette and alcohol use. The joint pharmacological effects of alcohol and nicotine on smoking and drinking motivation may help explain this relationship. This experiment was designed to test the separate and combined pharmacological effects of nicotine and a low dose of alcohol (equivalent to 1–2 standard drinks) on substance use motivation using a double-blind and fully-crossed within-subjects design. Participants (N = 87) with a wide range of smoking and drinking patterns completed four counter-balanced experimental sessions during which they consumed an alcohol (Male: 0.3 g/kg; Female: 0.27 g/kg) or placebo beverage and smoked a nicotine (.6 mg) or placebo cigarette. Outcome measures assessed the impact of drug administration (alcohol or nicotine) on craving to smoke, craving to drink, affect, and liking of the beverage and cigarette. Results indicated that combined administration produced higher cravings to smoke for the entire sample, as well as higher cravings to drink among women and lighter drinkers. Heavier users of either alcohol or cigarettes also exhibited enhanced sensitivity to the effects of either drug in isolation. Separate, but not interactive, effects of alcohol and nicotine on mood were observed, as well as both same-drug and cross-drug effects on beverage and cigarette liking. Together, these findings support the notion that the interactive pharmacological effects of nicotine and low-doses of alcohol play an important role in motivating contemporaneous use and suggest roles for cross-reinforcement and cross-tolerance in the development and maintenance of alcohol and nicotine use and dependence. PMID:24364618

Gambling disorder: a side effect of an off-label prescription of baclofen-literature review.

PubMed

Guillou-Landreat, Morgane; Victorri Vigneau, Caroline; Gerardin, Marie

2017-01-10

The use of high-dose baclofen emerged in 2008 in the treatment of alcohol-use disorders. Its prescription is still off-label in France, but recent trials have suggested the interest of using high doses for alcohol dependence, so we have to deal with an increase in its use. However, we still have few data about the adverse effects of a high-dose baclofen prescription, especially in complex addictive disorders. We present a case of a 32-year-old man who sought treatment for gambling disorders (GDs). He had complex addictive disorders, including alcohol-use disorders and GDs. He developed a severe GD, after treatment with a high dose of baclofen. The maximum dose was 160 mg/day, prescribed for his alcohol-use disorders. According to the Naranjo algorithm, the score was +7, it enabled to conclude that problem of gambling was probably imputable to baclofen. We discuss this case with reference to literature. 2017 BMJ Publishing Group Ltd.

Effects of Alcohol on Performance on a Distraction Task During Simulated Driving

PubMed Central

Allen, Allyssa J.; Meda, Shashwath A.; Skudlarski, Pawel; Calhoun, Vince; Astur, Robert; Ruopp, Kathryn C.; Pearlson, Godfrey D.

2009-01-01

Background Prior studies report that accidents involving intoxicated drivers are more likely to occur during performance of secondary tasks. We studied this phenomenon, using a dual-task paradigm, involving performance of a visual oddball (VO) task while driving in an alcohol challenge paradigm. Previous functional MRI (fMRI) studies of the VO task have shown activation in the anterior cingulate, hippocampus, and prefrontal cortex. Thus, we predicted dose-dependent decreases in activation of these areas during VO performance. Methods Forty healthy social drinkers were administered 3 different doses of alcohol, individually tailored to their gender and weight. Participants performed a VO task while operating a virtual reality driving simulator in a 3T fMRI scanner. Results Analysis showed a dose-dependent linear decrease in Blood Oxygen Level Dependent activation during task performance, primarily in hippocampus, anterior cingulate, and dorsolateral prefrontal areas, with the least activation occurring during the high dose. Behavioral analysis showed a dose-dependent linear increase in reaction time, with no effects associated with either correct hits or false alarms. In all dose conditions, driving speed decreased significantly after a VO stimulus. However, at the high dose this decrease was significantly less. Passenger-side line crossings significantly increased at the high dose. Conclusions These results suggest that driving impairment during secondary task performance may be associated with alcohol-related effects on the above brain regions, which are involved with attentional processing/decision-making. Drivers with high blood alcohol concentrations may be less able to orient or detect novel or sudden stimuli during driving. PMID:19183133

Response Inhibition Impairments Predict Alcohol-Induced Sedation

PubMed Central

Shannon, Erin E.; Staniforth, Elizabeth R.; McNamara, Juliette; Bernosky-Smith, Kimberly A.; Liguori, Anthony

2011-01-01

Aims: The aim of this study was to probe the relationship between the subjective effects of alcohol and impulsive behavior in social drinkers. Methods: Fifty social drinkers performed a response-inhibition task before consuming alcohol. A 0.8-g/kg dose of alcohol was administered in a binge-like fashion (0.2 g/kg every 30 min) to the participants over a 2-h time period. Participants then completed questionnaires measuring stimulation, sedation and mood following consumption of alcohol. Linear regression analyses were performed by examining the relationship between performance on the response inhibition impulsivity task and subjective responses to alcohol (i.e. stimulation, sedation and arousal). Results: There was a significant positive relationship found between impulsive responding and self-reported sedation following alcohol consumption. Additionally, there was a significant negative relationship between behavioral impulsivity and self-reported stimulation and arousal following alcohol consumption. Conclusion: These results suggest that higher levels of impulsivity are associated with experiencing greater sedating than stimulating effects of alcohol. Individuals with high levels of impulsivity may be less sensitive to the stimulating effects of a specified dose of alcohol, which could lead to these individuals consuming more alcohol to experience the stimulating effects of alcohol. PMID:21127353

Effects of Alcohol on Tests of Executive Functioning in Men and Women: A Dose Response Examination

PubMed Central

Guillot, Casey R.; Fanning, Jennifer R.; Bullock, Joshua S.; McCloskey, Michael S.; Berman, Mitchell E.

2014-01-01

Alcohol has been shown to affect performance on tasks associated with executive functioning. However, studies in this area have generally been limited to a single dose or gender or have used small sample sizes. The purpose of this study was to provide a more nuanced and systematic examination of alcohol's effects on commonly used tests of executive functioning at multiple dosages in both men and women. Research volunteers (91 women and 94 men) were randomly assigned to one of four drink conditions (alcohol doses associated with target blood alcohol concentrations of .000%, .050%, .075% and .100%). Participants then completed three tasks comprising two domains of executive functioning: two set shifting tasks, the Trail Making Test and a computerized version of the Wisconsin Card Sorting Task, and a response inhibition task, the GoStop Impulsivity Paradigm. Impaired performance on set shifting tasks was found at the .100% and .075% dosages, but alcohol intoxication did not impair performance on the GoStop. No gender effects emerged. Thus, alcohol negatively affects set shifting at moderately high levels of intoxication in both men and women, likely due to alcohol's interference with prefrontal cortex function. Although it is well-established that alcohol negatively affects response inhibition as measured by auditory stop-signal tasks, alcohol does not appear to exert a negative effect on response inhibition as measured by the GoStop, a visual stop-signal task. PMID:20939644

Effects of low doses of alcohol on driving-related skills : a review of the evidence

DOT National Transportation Integrated Search

1988-07-01

A large scale review of the experimental literature on alcohol effects on skills related to driving, considered 177 citations and explored the evidence of alcohol effects on reaction time, tracking, concentrated attention, divided attention performan...

Alcohol consumption impairs stimulus- and error-related processing during a Go/No-Go Task.

PubMed

Easdon, Craig; Izenberg, Aaron; Armilio, Maria L; Yu, He; Alain, Claude

2005-12-01

Alcohol consumption has been shown to increase the number of errors in tasks that require a high degree of cognitive control, such as a go/no-go task. The alcohol-related decline in performance may be related to difficulties in maintaining attention on the task at hand and/or deficits in inhibiting a prepotent response. To test these two accounts, we investigated the effects of alcohol on stimulus- and response-locked evoked potentials recorded during a go/no-go task that involved the withholding of key presses to rare targets. All participants performed the task prior to drinking and were then assigned randomly to either a control, low-dose, or moderate-dose treatment. Both doses of alcohol increased the number of errors relative to alcohol-free performance. Success in withholding a prepotent response was associated with an early-enhanced stimulus-locked negativity at inferior parietal sites, which was delayed when participants failed to inhibit the motor command. Moreover, low and moderate doses of alcohol reduced N170 and P3 amplitudes during go, no-go, and error trials. In comparison with the correct responses, errors generated large response-locked negative (Ne) and positive (Pe) waves at central sites. Both doses of alcohol reduced the Ne amplitude whereas the Pe amplitude decreased only after moderate doses of alcohol. These results are consistent with the interpretation that behavioral disinhibition following alcohol consumption involved alcohol-induced deficits in maintaining and allocating attention thereby affecting the processing of incoming stimuli and the recognition that an errant response has been made.

High-dose baclofen for the treatment of alcohol dependence (BACLAD study): a randomized, placebo-controlled trial.

PubMed

Müller, Christian A; Geisel, Olga; Pelz, Patricia; Higl, Verena; Krüger, Josephine; Stickel, Anna; Beck, Anne; Wernecke, Klaus-Dieter; Hellweg, Rainer; Heinz, Andreas

2015-08-01

Previous randomized, placebo-controlled trials (RCTs) assessing the efficacy of the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen in the treatment of alcohol dependence have reported divergent results, possibly related to the low to medium dosages of baclofen used in these studies (30-80mg/d). Based on preclinical observations of a dose-dependent effect and positive case reports in alcohol-dependent patients, the present RCT aimed to assess the efficacy and safety of individually titrated high-dose baclofen for the treatment of alcohol dependence. Out of 93 alcohol-dependent patients initially screened, 56 were randomly assigned to a double-blind treatment with individually titrated baclofen or placebo using dosages of 30-270mg/d. The multiple primary outcome measures were (1) total abstinence and (2) cumulative abstinence duration during a 12-week high-dose phase. More patients of the baclofen group maintained total abstinence during the high-dose phase than those receiving placebo (15/22, 68.2% vs. 5/21, 23.8%, p=0.014). Cumulative abstinence duration was significantly higher in patients given baclofen compared to patients of the placebo group (mean 67.8 (SD 30) vs. 51.8 (SD 29.6) days, p=0.047). No drug-related serious adverse events were observed during the trial. Individually titrated high-dose baclofen effectively supported alcohol-dependent patients in maintaining alcohol abstinence and showed a high tolerability, even in the event of relapse. These results provide further evidence for the potential of baclofen, thereby possibly extending the current pharmacological treatment options in alcohol dependence. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

In Utero Exposure to Low-Dose Alcohol Induces Reprogramming of Mammary Development and Tumor Risk in MMTV-erbB-2 Transgenic Mice

PubMed Central

Ma, Zhikun; Blackwelder, Amanda J.; Lee, Harry; Zhao, Ming; Yang, Xiaohe

2015-01-01

There is increasing evidence that prenatal exposure to environmental factors may modify breast cancer risk later in life. This study aimed to investigate the effects of in utero exposure to low-dose alcohol on mammary development and tumor risk. Pregnant MMTV-erbB-2 mice were exposed to alcohol (6 g/kg/day) between day 13 and day 19 of gestation, and the female offspring were examined for tumor risk. Whole mount analysis indicated that in utero exposure to low-dose alcohol induced significant increases in ductal extension at 10 weeks of age. Molecular analysis showed that in utero alcohol exposure induced upregulation of ERα signaling and activation of Akt and Erk1/2 in pubertal mammary glands. However, enhanced signaling in the EGFR/erbB-2 pathway appeared to be more prominent in 10-week-old glands than did signaling in the other pathways. Interestingly, tumor development in mice with in utero exposure to low-dose alcohol was slightly delayed compared to control mice, but tumor multiplicity was increased. The results indicate that in utero exposure to low-dose alcohol induces the reprogramming of mammary development by mechanisms that include altered signaling in the estrogen receptor (ER) and erbB-2 pathways. The intriguing tumor development pattern might be related to alcohol dose and exposure conditions, and warrants further investigation. PMID:25853264

Different contributions of dopamine D1 and D2 receptor activity to alcohol potentiation of brain stimulation reward in C57BL/6J and DBA/2J mice.

PubMed

Fish, Eric W; DiBerto, Jeffrey F; Krouse, Michael C; Robinson, J Elliott; Malanga, C J

2014-08-01

C57BL/6J (C57) and DBA/2J (DBA) mice respond differently to drugs that affect dopamine systems, including alcohol. The current study compared effects of D1 and D2 receptor agonists and antagonists, and the interaction between D1/D2 antagonists and alcohol, on intracranial self-stimulation in male C57 and DBA mice to determine the role of dopamine receptors in the effects of alcohol on brain stimulation reward (BSR). In the initial strain comparison, dose effects on BSR thresholds and maximum operant response rates were determined for the D1 receptor agonist SKF-82958 (±-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 0.1-0.56 mg/kg) and antagonist SCH 23390 (+-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepinehydrochloride; 0.003-0.056 mg/kg), and the D2 receptor agonist quinpirole (0.1-3.0 mg/kg) and antagonist raclopride (0.01-0.56 mg/kg). For the alcohol interaction, SCH 23390 (0.003 mg/kg) or raclopride (0.03 mg/kg) was given before alcohol (0.6-2.4 g/kg p.o.). D1 antagonism dose-dependently elevated and SKF-82958 dose-dependently lowered BSR threshold in both strains; DBA mice were more sensitive to SKF-82958 effects. D2 antagonism dose-dependently elevated BSR threshold only in C57 mice. Low doses of quinpirole elevated BSR threshold equally in both strains, whereas higher doses of quinpirole lowered BSR threshold only in C57 mice. SCH 23390, but not raclopride, prevented lowering of BSR threshold by alcohol in DBA mice. Conversely, raclopride, but not SCH 23390, prevented alcohol potentiation of BSR in C57 mice. These results extend C57 and DBA strain differences to D1/D2 sensitivity of BSR, and suggest differential involvement of D1 and D2 receptors in the acute rewarding effects of alcohol in these two mouse strains. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Nicotine interactions with low-dose alcohol: pharmacological influences on smoking and drinking motivation.

PubMed

Oliver, Jason A; Blank, Melissa D; Van Rensburg, Kate Janse; MacQueen, David A; Brandon, Thomas H; Drobes, David J

2013-11-01

An extensive literature documents a close association between cigarette and alcohol use. The joint pharmacological effects of alcohol and nicotine on smoking and drinking motivation may help explain this relationship. This experiment was designed to test the separate and combined pharmacological effects of nicotine and a low dose of alcohol (equivalent to 1-2 standard drinks) on substance use motivation using a double-blind and fully crossed within-subjects design. Participants (N = 87) with a wide range of smoking and drinking patterns completed 4 counterbalanced experimental sessions during which they consumed an alcohol (male: 0.3g/kg; female: 0.27g/kg) or placebo beverage and smoked a nicotine (.6 mg) or placebo cigarette. Outcome measures assessed the impact of drug administration (alcohol or nicotine) on craving to smoke, craving to drink, affect, and liking of the beverage and cigarette. Results indicated that combined administration produced higher cravings to smoke for the entire sample, as well as higher cravings to drink among women and lighter drinkers. Heavier users of either alcohol or cigarettes also exhibited enhanced sensitivity to the effects of either drug in isolation. Separate, but not interactive, effects of alcohol and nicotine on mood were observed as well as both same-drug and cross-drug effects on beverage and cigarette liking. Together, these findings support the notion that the interactive pharmacological effects of nicotine and low doses of alcohol play an important role in motivating contemporaneous use and suggest roles for cross-reinforcement and cross-tolerance in the development and maintenance of alcohol and nicotine use and dependence. PsycINFO Database Record (c) 2013 APA, all rights reserved.

The dose-effect relationship of baclofen in alcohol dependence: A 1-year cohort study.

PubMed

Pignon, Baptiste; Labreuche, Julien; Auffret, Marine; Gautier, Sophie; Deheul, Sylvie; Simioni, Nicolas; Cottencin, Olivier; Bordet, Régis; Duhamel, Alain; Rolland, Benjamin

2017-07-01

Our aim is to study the relationship between dose of baclofen and effectiveness in alcohol dependence. Two hundred two patients with alcohol dependence, who received baclofen treatment for drinking reduction, were followed up for 1 year. For each patient-month of treatment, the maximum daily dose of baclofen (DDB) and average weekly alcohol consumption (AWAC) were calculated. We defined a favorable drinking outcome as an AWAC under 200 g/w for at least 2 consecutive months. We divided the DDB of each patient-month into 3 categories (low dose: <90 mg/d, medium dose: 90-150 mg/d, and high dose: >150 mg/d) and investigated the relationship between reaching a favorable outcome and the concurrent DDB category in a time-varying Cox regression analysis. Hazard ratios (HRs) were adjusted based on age, sex, and initial AWAC. One hundred forty subjects were followed during at least 1 month. Of these patients, 58 (41%) had a favorable drinking outcome. In comparison to low dose, medium dose was associated with a decreased rate of favorable drinking outcome (HR = 0.42; 95% CI [0.20, 0.88]), whereas no difference was found with high dose (HR = 1.31; 95% CI [0.65, 2.64]). The relationship between dose of baclofen and favorable drinking outcome was U-shaped, that is, was increased at low and high doses compared to medium doses. Copyright © 2017 John Wiley & Sons, Ltd.

Protective effect of artemisinin on chronic alcohol induced-liver damage in mice.

PubMed

Zhao, Xiaoyan; Wang, Liqing; Zhang, Hao; Zhang, Duoduo; Zhang, Zhihao; Zhang, Jie

2017-06-01

The liver disease related to chronic alcohol consumption is one of the leading causes of death for alcoholics. The efficient drug to ameliorate the alcoholic liver injury was needed urgently. The present study was performed to investigate whether artemisinin possessed the protective effect against chronic alcohol consumption. 50 male Kunming mice were divided into 5 groups: control group (C): 10ml/kg saline+10ml/kg saline, alcohol group (A): 10ml/kg 56%(v/v) alcohol+10ml/kg saline, low dose group of artemisinin (L): 10ml/kg 56%(v/v) alcohol+30mg/kg/day artemisinin, medium dose group of artemisinin (M): 10ml/kg 56%(v/v) alcohol+60mg/kg/day artemisinin, high dose group of artemisinin (H): 10ml/kg 56%(v/v) alcohol+120mg/kg/day artemisinin. Drugs were given orally every day. The general state of mice was observed and the levels of serum activities of AST and ALT were detected after treatment with drugs for 30days. Besides, the liver weight index was calculated and histopathological analysis was performed. We successfully demonstrated that treatment with high dose of artemisinin significantly decreased the elevated levels of AST (p<0.05) and ALT (p<0.01) in plasma, as well as the liver weight index (p<0.01). The loss of body weight, tissue injury, oedema and inflammatory cell infiltration in the hepatocytes were found in the A group. These symptoms were remarkably alleviated in animals treated with artemisinin. Artemisinin can inhibit the activation of NF-кB and the expression of inflammatory cytokines inducible nitric oxide synthase. Besides, it can also enhance the stability of liver cell membrane, and reduce the damage of liver cell membrane and liver cell. Artemisinin showed a protective effect against chronic alcohol poisoning and it has a great potential for the clinical application to treat the liver injury induced by alcohol. Copyright © 2017 Elsevier B.V. All rights reserved.

Erysodine, a competitive antagonist at neuronal nicotinic acetylcholine receptors, decreases ethanol consumption in alcohol-preferring UChB rats.

PubMed

Quiroz, Gabriel; Guerra-Díaz, Nicolás; Iturriaga-Vásquez, Patricio; Rivera-Meza, Mario; Quintanilla, María Elena; Sotomayor-Zárate, Ramón

2018-09-03

Alcohol abuse is a worldwide health problem with high economic costs to health systems. Emerging evidence suggests that modulation of brain nicotinic acetylcholine receptors (nAChRs) may be a therapeutic target for alcohol dependence. In this work, we assess the effectiveness of four doses of erysodine (1.5, 2.0, 4.0 or 8.0 mg/kg/day, i.p.), a competitive antagonist of nAChRs, on voluntary ethanol consumption behavior in alcohol-preferring UChB rats, administered during three consecutive days. Results show that erysodine administration produces a dose-dependent reduction in ethanol consumption respect to saline injection (control group). The highest doses of erysodine (4 and 8 mg/kg) reduce (45 and 66%, respectively) the ethanol intake during treatment period and first day of post-treatment compared to control group. While, the lowest doses of erysodine (1.5 and 2 mg/kg) only reduce ethanol intake during one day of treatment period. These effective reductions in ethanol intake were 23 and 29% for 1.5 and 2 mg/kg erysodine, respectively. Locomotor activity induced by a high dose of erysodine (10 mg/kg) was similar to those observed with saline injection in control rats, showing that the reduction in ethanol intake was not produced by hypolocomotor effect induced by erysodine. This is the first report showing that erysodine reduces ethanol intake in UChB rats in a dose-dependent manner. Our results highlight the role of nAChRs in the reward effects of ethanol and its modulation as a potentially effective pharmacological alternative for alcohol dependence treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of alcohol dose on deliberate self-harm in men and women.

PubMed

Berman, Mitchell E; Fanning, Jennifer R; Guillot, Casey R; Marsic, Angelika; Bullock, Joshua; Nadorff, Michael R; McCloskey, Michael S

2017-09-01

Nonexperimental survey and field research support the notion that alcohol use may be associated with deliberate self-harm (DSH) across the spectrum of lethality, from nonsuicidal self-injury (NSSI) through suicide. Nonexperimental studies, however, provide limited information about potential causal relationships between alcohol consumption and DSH. Two previous experiments showed that a relatively high-dose of alcohol increases the likelihood of engaging in DSH in men, with DSH defined by the self-administration of a "painful" shock (the self-aggression paradigm [SAP]; Berman & Walley, 2003; McCloskey & Berman, 2003). In this study, we examined whether (a) lower doses of alcohol also elicit DSH, (b) this effect occurs for women as well as men, and (c) individual differences in past nonsuicidal self-injury (NSSI) moderate alcohol's effects on DSH. Nonalcohol dependent men and women (N = 210) were assigned either to .00%, .05%, .075%, or .100% blood alcohol concentration (BAC) drink conditions and completed a self-rating scale of NSSI (the Deliberate Self-Harm Inventory [DSHI]; Gratz, 2001). As in previous SAP studies, DSH was operationalized by shock setting behavior during a competitive reaction time (RT) game. Overall, a greater proportion of participants in the .075% and .100% (but not .050%) alcohol conditions self-selected a "painful" shock to administer compared to participants in the placebo condition. NSSI predicted self-administration of painful shocks, but did not moderate the alcohol effect. Results provide experimental evidence to support the notion that interventions for self-harm should include processes to monitor and limit alcohol intake. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Possibility as monosaccharide laxative of rare sugar alcohols.

PubMed

Oosaka, Kazumasa

2009-05-01

Allitol, D-talitol and L-iditol are sugar alcohols that are rare in nature. Due to their previous rarity, little is known about the laxative effects of these rare sugar alcohols. Therefore, reliable data on the laxative effect that these sugar alcohols cause in experimental animals could help to evaluate the effectiveness of new monosaccharide laxative drugs. To investigate the laxative effect of rare sugar alcohols, the study was designed to observe the diarrhea that occurred after oral administration of these sugar alcohols in mice. Moreover, to investigate the influence on intestinal function of rare sugar alcohols, the study was designed to examine small intestine transit and the luminal water content. Results indicated that rare sugar alcohols have a laxative effect in mice. Diarrhea started at a dose of 4.95 g/kg of rare sugar alcohols. There was a statistically significant laxative effect for D-talitol and L-iditol at a dose of 9.9 g/kg as compared to vehicle. Moreover, rare sugar alcohols significantly increased the small intestinal transit and the luminal water content of the small intestine and cecum in mice as compared to each vehicle. Overall, L-iditol greatly changes the function of intestine. In conclusion, rare sugar alcohols increase water content in small intestine and accelerate small intestine transit. These results support laxative effect of rare sugar alcohols. Therefore, rare sugar alcohols may be useful as monosaccharide laxatives and may be used to treat constipation.

Potentiation of low dose ketamine effects by naltrexone: potential implications for the pharmacotherapy of alcoholism.

PubMed

Krystal, John H; Madonick, Steven; Perry, Edward; Gueorguieva, Ralitza; Brush, Laura; Wray, Yola; Belger, Aysenil; D'Souza, Deepak Cyril

2006-08-01

The interplay of opiate and NMDA glutamate receptors may contribute to psychosis, cognitive function, alcoholism, and substance dependence. Ketamine and ethanol block the NMDA glutamate receptor. The purpose of this randomized double-blind, placebo-controlled human laboratory study was to evaluate whether the interactive effects of drugs acting at opiate and NMDA glutamate receptors might partially explain the efficacy of naltrexone for the treatment of alcoholism, that is, whether naltrexone 25 mg pretreatment would modulate ketamine effects in healthy human subjects. Two groups of healthy subjects were studied. An initial group (n=31) received a perception-altering subanesthetic dose of ketamine (bolus of 0.23 mg/kg over 1 min followed by a 60-min infusion of 0.58 mg/kg or saline bolus and infusion). A second group (n=24) completed the same testing procedures, but received a subperceptual ketamine dose (bolus 0.081 mg/kg over 10 min followed by an infusion of 0.4 mg/kg/h). Ketamine produced positive symptoms, negative symptoms, emotional discomfort, and cognitive effects as measured by the Positive and Negative Syndrome Scale (PANSS) in a dose-related fashion. The lower ketamine dose produced subjective effects similar to two standard ethanol drinks, whereas the higher ketamine dose produced effects similar to five standard drinks. Although naltrexone produced no significant behavioral effects, it significantly magnified the increase in the total PANSS score produced by the lower subperceptual dose of ketamine, but not the higher perception-altering dose of ketamine. These data suggest that the interplay of opiate receptor antagonism and NMDA receptor antagonism may be relevant to the protective effects of naltrexone on alcohol consumption via potentiation of dysphoric effects associated with the NMDA receptor antagonist effects of ethanol. However, these data suggest that at levels of NMDA receptor antagonism associated with heavy drinking, this protective effect of naltrexone on drinking is no longer present.

Subjective Effects of Thiopental in Young Adults with and without a Family History of Alcoholism

PubMed Central

Petrakis, Ismene L; Kerfoot, Karin; Pittman, Brian; Perrino, Albert; Koretski, Julia; Newcomb, Jenelle; Limoncelli, Diana; Acampora, Gregory; Ralevski, Elizabeth

2013-01-01

Background The development of alcohol use disorders is genetically influenced, and may be mediated through differences in the subjective response to alcohol. There is some evidence to suggest that response differences to alcohol could be conveyed by heritable differences in GABAA receptors. The purpose of this study was to investigate whether individuals with a family history positive (FHP) for alcohol dependence would experience alterations in response to the GABAA receptor agonist thiopental, in comparison to family history negative (FHN) subjects. Methods 73 subjects (24 FHP and 49 FHN) between the ages of 21 and 30 years were administered sub-anesthetic doses of the GABAA receptor agonist thiopental and placebo on two separate test days. Various alcohol-related measures were administered, including those examining subjective effects, coordination, and cognition. Results Sub-anesthetic doses of thiopental produced alcohol-like subjective effects, as well as alcohol-like impaired coordination and cognition in healthy subjects. While there were no significant main effects in subjective, coordination, or cognitive effects between FHP and FHN individuals, analysis of peak effects suggested FHP had blunted sedative, but not stimulant effects compared to FHN. Conclusion Thiopental produced alcohol-like effects and perceived similarities to alcohol in healthy individuals. Subtle differences in sedative effects are consistent with reports of blunted FHP response to the negative but not stimulant effects of alcohol. Future studies are needed to better understand how this insight informs our understanding of the heritable risk for alcoholism and the treatment of alcohol use disorders. PMID:24273687

Alcohol calibration of tests measuring skills related to car driving.

PubMed

Jongen, Stefan; Vuurman, Eric; Ramaekers, Jan; Vermeeren, Annemiek

2014-06-01

Medication and illicit drugs can have detrimental side effects which impair driving performance. A drug's impairing potential should be determined by well-validated, reliable, and sensitive tests and ideally be calibrated by benchmark drugs and doses. To date, no consensus has been reached on the issue of which psychometric tests are best suited for initial screening of a drug's driving impairment potential. The aim of this alcohol calibration study is to determine which performance tests are useful to measure drug-induced impairment. The effects of alcohol are used to compare the psychometric quality between tests and as benchmark to quantify performance changes in each test associated with potentially impairing drug effects. Twenty-four healthy volunteers participated in a double-blind, four-way crossover study. Treatments were placebo and three different doses of alcohol leading to blood alcohol concentrations (BACs) of 0.2, 0.5, and 0.8 g/L. Main effects of alcohol were found in most tests. Compared with placebo, performance in the Divided Attention Test (DAT) was significantly impaired after all alcohol doses and performance in the Psychomotor Vigilance Test (PVT) and the Balance Test was impaired with a BAC of 0.5 and 0.8 g/L. The largest effect sizes were found on postural balance with eyes open and mean reaction time in the divided attention and the psychomotor vigilance test. The preferable tests for initial screening are the DAT and the PVT, as these tests were most sensitive to the impairing effects of alcohol and being considerably valid in assessing potential driving impairment.

Effects of caffeine on alcohol consumption and nicotine self-administration in rats.

PubMed

Rezvani, Amir H; Sexton, Hannah G; Johnson, Joshua; Wells, Cori; Gordon, Karen; Levin, Edward D

2013-09-01

Caffeine, alcohol, and nicotine are 3 of the most widespread self-administered psychoactive substances, which are known to be extensively co-administered. However, little is known about the degree to which they may mutually potentiate each other's consumption. In the current set of studies, we examined in rats the effect of caffeine administration on alcohol drinking and intravenous (i.v.) self-administration of nicotine. In male alcohol-preferring (P) rats, caffeine (5, 10, and 20 mg/kg) or the saline vehicle was administered acutely either by subcutaneous (S.C.) injection or orally (PO) by gavage. In a chronic study, the effect of PO caffeine (5 and 20 mg/kg) on alcohol intake over a 10-day period was tested. In another experiment, the effect of acute PO administration of caffeine (20 mg/kg) or saline on saccharin intake (0.2% solution) was determined in P rats. Effects of 20 mg/kg caffeine on motor activity were also determined in P rats. Finally, the effects of acute PO caffeine administration on nicotine self-administration in Sprague-Dawley rats were also determined. Both routes of administration of caffeine, S.C. and PO, caused a significant dose-related decrease in alcohol intake and preference during free access to alcohol and after 4-day deprivation of alcohol. However, the low dose of 5 mg/kg caffeine increased alcohol intake. Acute PO caffeine also reduced saccharin intake. Acute systemic administration of 20 mg/kg caffeine did not exert a significant effect on motor activity. In Sprague-Dawley rats trained to self-administer i.v. nicotine, acute PO administration of caffeine significantly increased self-administration of nicotine in a dose-related manner. These results suggest that adenosine receptor systems may play a role in both alcohol and nicotine intake and deserve further study regarding these addictions. Copyright © 2013 by the Research Society on Alcoholism.

Tolerability of High-dose Baclofen in the Treatment of Patients with Alcohol Disorders: A Retrospective Study.

PubMed

Rigal, Laurent; Legay Hoang, Léa; Alexandre-Dubroeucq, Constance; Pinot, Juliette; Le Jeunne, Claire; Jaury, Philippe

2015-09-01

The aim of this study was to describe the tolerability of high-dose baclofen taken by patients with alcohol disorders during their first year of treatment. The medical records of all patients prescribed baclofen by one general practitioner were examined and all patients who could be contacted were retrospectively interviewed about adverse effects. Of the 146 eligible patients, 116 (79%) could be interviewed. Ninety (78%) reported at least one adverse effect (mean number per patient: 2.8 ± 2.7). The mean dosage of baclofen at the onset of the first adverse effect was 83 ± 57 mg/day. The most frequent group of adverse effects involved disruption of the wake-sleep cycle and affected 73 patients (63%). Persistent adverse effects occurred in 62 patients (53%). Eight patients (7%) had adverse effects that led them to stop taking baclofen. Their dosages were <90 mg/day at that time. Alertness disorders and depression were the adverse effects that most frequently led to stopping baclofen. Bouts of somnolence and hypomanic episodes were the most potentially dangerous adverse effects. Women reported significantly more adverse effects than men. High-dose baclofen exposes patients with alcohol disorders to many adverse effects. Generally persistent, some adverse effects appear at low doses and may be dangerous. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Effects of artificial sweeteners on breath alcohol concentrations in male and female social drinkers.

PubMed

Stamates, Amy L; Maloney, Sarah F; Marczinski, Cecile A

2015-12-01

Alcohol is often mixed with various nonalcoholic beverages. While consumption of food with alcohol will decrease peak breath alcohol concentrations (BrAC), recent evidence has suggested that mixing alcohol with diet beverages can result in higher BrAC when compared with mixing the same amount of alcohol with sweetened beverages. The purpose of this study was to examine this phenomenon using two different moderate alcohol doses. Twenty participants (10 males) attended five sessions where they received 1 of 5 doses (0.91 ml/kg vodka+3.64 ml/kg of diet soda, 0.91 ml/kg vodka+3.64 of regular soda, 1.82 ml/kg vodka+7.28 ml/kg diet soda, 1.82 ml/kg vodka+7.28 ml/kg regular soda, and a placebo beverage). BrAC was recorded repeatedly up to 180 min after dose administration. Participants had significantly higher BrAC when the mixer was diet as compared to regular for both alcohol dose conditions. No gender differences were observed. Mixing alcohol with diet beverages can result in higher BrAC when compared to the same amount of alcohol administered with a similar sweetened beverage. Individuals who consume diet mixers with alcohol may reduce caloric intake but increase the harms associated with higher BrACs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Acute Interaction of Baclofen in Combination with Alcohol in Heavy Social Drinkers

PubMed Central

Evans, Suzette M.; Bisaga, Adam

2008-01-01

Background There is growing evidence that GABA-B receptor agonists may be effective in the treatment of alcohol abuse or dependence. The primary goal of this study was to determine the safety of baclofen in combination with alcohol consumption in heavy drinkers. In addition, the effects of baclofen alone, and in combination with alcohol, on subjective effects, cognitive performance effects, as well as alcohol craving, were assessed. Methods Eighteen non-treatment seeking heavy social drinkers (mean of 28 drinks/week) who did not meet criteria for alcohol dependence participated. All individuals were tested using a double-blind double-dummy design with six 2-day inpatient phases. Baclofen (0, 40, and 80 mg) was administered 2.5 hours before alcohol (1.5 g/l body water or approximately 0.75 g/kg) or placebo beverages, given in 4 divided doses every 20 min. Results Baclofen, either alone, or in combination with alcohol, produced only modest increases in heart rate and blood pressure and no adverse effects were reported. Baclofen did not increase positive subjective effects (e.g., Stimulant effects, Drug Liking) but did increase sedation and impair performance. Even though both baclofen and alcohol impaired performance, for the most part performance was not impaired to a greater extent when baclofen was combined with alcohol. Among this population of non-dependent drinkers, baclofen did not alter alcohol craving or alcohol-induced positive subjective effects. Conclusions Baclofen alone has minimal abuse liability in heavy social drinkers and baclofen is relatively well tolerated and safe when given in combination with intoxicating doses of alcohol. PMID:18840257

Effects of low-dose alcohol exposure on simulated merchant ship piloting by maritime cadets.

PubMed

Howland, J; Rohsenow, D J; Cote, J; Gomez, B; Mangione, T W; Laramie, A K

2001-03-01

The US Department of Transportation (DOT) regulates on-the-job alcohol use by operators of certain categories of commercial transport. For aircraft, trains, and commercial vessels, operators are subject to sanctions for having > or = 0.04 g% blood alcohol concentration (BAC). This study examines the effects of alcohol (between 0.04 and 0.05 g% BAC) on simulated merchant ship handling. A two-group randomized factorial design was used to compare beverage alcohol to placebo while controlling for baseline performance on a previous day. The study was conducted in the Maritime Simulation Center at Maine Maritime Academy, Castine, ME. Participants were 38 volunteer deck officer cadets in their junior or senior year, at least 21 years of age, with previous experience on a bridge simulator. Following a baseline trial on Day 1, on Day 2 participants were randomized to receive alcohol (0.6 g/kg for males and 0.5 g/kg for females) or placebo. After allowing time for absorption, participants completed a bridge simulator task. For baseline and performance trials, participants were randomized to one of four bridge simulator scenarios, each representing passage of a fully loaded container vessel through a channel with commercial traffic. The aggregate scenario score given by blinded maritime educators measured performance. A main effect for alcohol was found indicating that performance was significantly impaired by this low dose of alcohol relative to performance in the placebo condition. These findings are consistent with current federal regulations that limit low-dose alcohol exposure for the operators of commercial transport vehicles. Further research is required to determine effects at lower BACs.

Acute effects of alcohol on intrusive memory development and viewpoint dependence in spatial memory support a dual representation model.

PubMed

Bisby, James A; King, John A; Brewin, Chris R; Burgess, Neil; Curran, H Valerie

2010-08-01

A dual representation model of intrusive memory proposes that personally experienced events give rise to two types of representation: an image-based, egocentric representation based on sensory-perceptual features; and a more abstract, allocentric representation that incorporates spatiotemporal context. The model proposes that intrusions reflect involuntary reactivation of egocentric representations in the absence of a corresponding allocentric representation. We tested the model by investigating the effect of alcohol on intrusive memories and, concurrently, on egocentric and allocentric spatial memory. With a double-blind independent group design participants were administered alcohol (.4 or .8 g/kg) or placebo. A virtual environment was used to present objects and test recognition memory from the same viewpoint as presentation (tapping egocentric memory) or a shifted viewpoint (tapping allocentric memory). Participants were also exposed to a trauma video and required to detail intrusive memories for 7 days, after which explicit memory was assessed. There was a selective impairment of shifted-view recognition after the low dose of alcohol, whereas the high dose induced a global impairment in same-view and shifted-view conditions. Alcohol showed a dose-dependent inverted "U"-shaped effect on intrusions, with only the low dose increasing the number of intrusions, replicating previous work. When same-view recognition was intact, decrements in shifted-view recognition were associated with increases in intrusions. The differential effect of alcohol on intrusive memories and on same/shifted-view recognition support a dual representation model in which intrusions might reflect an imbalance between two types of memory representation. These findings highlight important clinical implications, given alcohol's involvement in real-life trauma. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Preliminary findings on the interactive effects of IV ethanol and IV nicotine on human behavior and cognition: a laboratory study.

PubMed

Ralevski, Elizabeth; Perry, Edward B; D'Souza, D Cyril; Bufis, Vanessa; Elander, Jacqueline; Limoncelli, Diana; Vendetti, Michael; Dean, Erica; Cooper, Thomas B; McKee, Sherry; Petrakis, Ismene

2012-05-01

There are mixed reports on nicotine's effects on alcohol-induced impairment in cognitive performance and behavior in humans. The main objective of this study was to characterize the interactive effects of acute intravenous (IV) alcohol and nicotine administration on behavior and cognition in healthy nonsmokers. Healthy subjects aged 21-44 years participated in 3 test days. On each test day, they received in a double-blind randomized manner one of three IV alcohol infusion conditions using a "clamp": placebo, targeted breathalyzer of 40 mg%, or targeted breathalyzer of 80 mg%. Alcohol infusion was delivered over 20 min and lasted for 120 min. They also received both placebo and active nicotine in a fixed order delivered intravenously. Placebo nicotine was delivered first over 10 min at the timepoint when the breath alcohol was "clamped"; active nicotine (1.0 mcg/kg/min) was delivered for 10 min, 70 min after the alcohol infusion was clamped. Subjective effects of alcohol were measured using the Biphasic Alcohol Effects Scale and the Number of Drinks Scale. Cognitive inhibition and attention were measured by the Continuous Performance Task-Identical Pairs and working memory by the Rey Auditory Verbal Learning Task (RAVLT). Nicotine significantly reversed subjective intoxication and sedation of alcohol at the low dose. Alcohol impaired performance on the RAVLT, and nicotine further impaired verbal learning and recall at both doses of alcohol. The data showed that nicotine had an effect on subjective alcohol effects but did not reverse and actually worsened alcohol-induced deficits in memory.

Environmental Enrichment Alters Neurotrophin Levels After Fetal Alcohol Exposure in Rats

PubMed Central

Parks, Elizabeth A.; McMechan, Andrew P.; Hannigan, John H.; Berman, Robert F.

2014-01-01

Background Prenatal alcohol exposure causes abnormal brain development, leading to behavioral deficits, some of which can be ameliorated by environmental enrichment. As both environmental enrichment and prenatal alcohol exposure can individually alter neurotrophin expression, we studied the interaction of prenatal alcohol and postweaning environmental enrichment on brain neurotrophin levels in rats. Methods Pregnant rats received alcohol by gavage, 0, 4, or 6 g / kg / d (Zero, Low, or High groups), or no treatment (Naïve group), on gestational days 8 to 20. After weaning on postnatal day 21, offspring were housed for 6 weeks in Isolated, Social, or Enriched conditions. Levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were then measured in frontal cortex, occipital cortex, hippocampus, and cerebellar vermis. Results Prenatal alcohol exposure increased NGF levels in frontal cortex (High-dose group) and cerebellar vermis (High- and Low-dose groups); increased BDNF in frontal cortex, occipital cortex and hippocampus (Low-dose groups), and increased NT-3 in hippocampus and cerebellar vermis (High-dose). Environmental enrichment resulted in lower NGF, BDNF, and NT-3 levels in occipital cortex and lower NGF in frontal cortex. The only significant interaction between prenatal alcohol treatment and environment was in cerebellar vermis where NT-3 levels were higher for enriched animals after prenatal alcohol exposure, but not for animals housed under Isolated or Social conditions. Conclusions Both prenatal alcohol exposure and postweaning housing conditions alter brain neurotrophin levels, but the effects appear to be largely independent. Although environmental enrichment can improve functional outcomes, these results do not provide strong support for the hypothesis that rearing in a complex environment ameliorates prenatal alcohol effects on brain neurotrophin levels in rats. PMID:18652597

Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response.

PubMed

Nikolaou, Kyriaki; Critchley, Hugo; Duka, Theodora

2013-01-01

Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4 g/kg or 0.8 g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI) data. The two task variants differed only in their instructions: in the classic variant (VSST), participants inhibited their response to a "Go-stimulus" when it was followed by a "Stop-stimulus". In the control variant (VSST_C), participants responded to the "Go-stimulus" even if it was followed by a "Stop-stimulus". Comparison of successful Stop-trials (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have little impact on the early visual processing of infrequent perceptual cues. These observations clarify clinically-important effects of alcohol on behaviour.

Visual search and urban driving under the influence of marijuana and alcohol.

PubMed

Lamers, C. T. J.; Ramaekers, J. G.

2001-07-01

The purpose of the present study was to assess the effects of low doses of marijuana and alcohol, and their combination, on visual search at intersections and on general driving proficiency in the City Driving Test. Sixteen recreational users of alcohol and marijuana (eight males and eight females) were treated with these substances or placebo according to a balanced, 4-way, cross-over, observer- and subject-blind design. On separate evenings, subjects received weight-calibrated doses of THC, alcohol or placebo in each of the following treatment conditions: alcohol placebo + THC placebo, alcohol + THC placebo, THC 100 &mgr;g/kg + alcohol placebo, THC 100 &mgr;g/kg + alcohol. Alcohol doses administered were sufficient for achieving a blood alcohol concentration (BAC) of about 0.05 g/dl. Initial drinking preceded smoking by one hour. The City Driving Test commenced 15 minutes after smoking and lasted 45 minutes. The test was conducted over a fixed route within the city limits of Maastricht. An eye movement recording system was mounted on each subject's head for providing relative frequency measures of appropriate visual search at intersections. General driving quality was rated by a licensed driving instructor on a shortened version of the Royal Dutch Tourist Association's Driving Proficiency Test. After placebo treatment subjects searched for traffic approaching from side streets on the right in 84% of all cases. Visual search frequency in these subjects did not change when they were treated with alcohol or marijuana alone. However, when treated with the combination of alcohol and marijuana, the frequency of visual search dropped by 3%. Performance as rated on the Driving Proficiency Scale did not differ between treatments. It was concluded that the effects of low doses of THC (100 &mgr;g/kg) and alcohol (BAC < 0.05 g/dl) on higher-level driving skills as measured in the present study are minimal. Copyright 2001 John Wiley & Sons, Ltd.

[Dose effect of alcohol on sex differences in blood alcohol metabolism--cases where healthy subjects with ALDH2*1/1 genotype drunk beer with meal].

PubMed

Oshima, Shunji; Haseba, Takeshi; Masuda, Chiaki; Kakimi, Ema; Kitagawa, Yasushi; Ohno, Youkichi

2013-06-01

It is said that blood alcohol concentrations (BAG) are higher in female than in male due to the smaller distribution volume of alcohol in female, whereas the rate of alcohol metabolism is faster in female than in males due to a higher activity of liver alcohol dehydrogenase (ADH) in female. However, it is also known that alcohol metabolism varies depending on drinking conditions. In this study, we evaluated the dose effect of alcohol on sex differences in alcohol metabolism in daily drinking conditions, where young adults (16 males, 15 females) with ALDH2*1/1 genotype drunk beer at a dose of 0.32g or 1.0g ethanol/kg body weight with a test meal (460kcal). This study was conducted using a randomized cross-over design. In the considerable drinking condition (1.0g/kg), BAG was significantly higher in females than in males, whereas the rate of alcohol metabolism (beta) was higher in female than in male. In the moderate drinking condition (0.32g/kg), however, no sex differences in alcohol metabolism including BAG were seen. These results suggest that an increased first pass metabolism through liver ADH in female, which may be caused by the reduction of gastric emptying rate due to the meal intake, contribute to the vanishing of sex difference in BAC in the moderate drinking condition.

Effects of neuropeptide Y and ethanol on arousal and anxiety-like behavior in alcohol-preferring rats.

PubMed

Gilpin, Nicholas W; Henderson, Angela N; Badia-Elder, Nancy E; Stewart, Robert B

2011-03-01

Neuropeptide Y (NPY) is abundant in the mammalian brain and plays a prominent role in behaviors related to negative affect and alcohol. NPY suppresses anxiety-like behavior and alcohol-drinking behaviors in a wide array of rodent models and also affects changes in these behaviors produced by fearful and stressful stimuli. Rats selectively bred for high alcohol preference (P rats) appear to be particularly sensitive to the behavioral effects of NPY. The dual purpose of the present investigation was to determine the effects of intraventricular NPY on (1) the acoustic startle response (ASR) of P rats in a high-anxiety setting and (2) social interaction behavior of P rats. In experiment 1, P rats were either cycled through periods of long-term ethanol access and abstinence or they remained ethanol naive. Rats were injected with one of four NPY doses and tested for ASR before and after footshock stress. NPY suppressed ASR in all P rats regardless of shock condition or drinking history. In experiment 2, rats received intraventricular infusion of one of four NPY doses and were then injected with either ethanol (0.75 g/kg) or saline and tested for social interaction. NPY increased social interaction in P rats even at doses that suppressed locomotor activity, regardless of ethanol dose. Suppression of anxiety-like and arousal behaviors by NPY in the present study confirm a role for NPY in alcohol-related behaviors in alcohol-preferring P rats. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of sibutramine alone and with alcohol on cognitive function in healthy volunteers

PubMed Central

Wesnes, K A; Garratt, C; Wickens, M; Gudgeon, A; Oliver, S

2000-01-01

Aims To investigate the effects of sibutramine in combination with alcohol in a double-blind, randomised, placebo-controlled, four-way crossover study in 20 healthy volunteers. Methods On each study day each volunteer received either: sibutramine 20 mg+0.5 g kg−1 alcohol; sibutramine 20 mg+placebo alcohol; placebo capsules+0.5 g kg−1 alcohol; or placebo capsules+placebo alcohol. Alcohol was administered 2 h following ingestion of the study capsules. During each study day, assessments of cognitive performance were made prior to dosing, and at 3, 4.5, 6 and 10 h post dosing. Blood alcohol concentration was estimated using a breath alcometer immediately prior to each cognitive performance test session. Each study day was followed by a minimum 7 day washout period. Results Alcohol was found to produce statistically significant impairments in tests of attention (maximum impairment to speed of digit vigilance=49 ms) and episodic memory (maximum impairment to speed of word recognition=74 ms). Alcohol also increased body sway (maximum increase 17.4 units) and lowered self rated alertness (maximum decrease 13.6 mm). These effects were produced by an inferred blood alcohol level of 53.2 mg dl−1.Sibutramine was not found to potentiate any of the effects of alcohol. There was a small, yet statistically significant, interaction effect observed on the sensitivity index of the picture recognition task. In this test, the combined effects of sibutramine and alcohol were smaller than the impairments produced by alcohol alone. Sibutramine, when dosed alone, was associated with improved performance on several tasks. Sibutramine improved attention (mean speed of digit vigilance improved by 21 ms), picture recognition speed (improvement at 3=81) and motor control (tracking error at 3 h reduced by 1.58 mm). Also sibutramine improved postural stability (reducing body sway at 3 h by 14.2 units). Adverse events reported were unremarkable and consistent with the known pharmacology of sibutramine and alcohol. Conclusions There was little evidence of a clinically relevant interaction of sibutramine with the impairment of cognitive function produced by alcohol in healthy volunteers. The single statistically significant interaction indicated a reduction, rather than a worsening, of alcohol-induced impairment when sibutramine is taken concomitantly. Sibutramine when administered alone is associated with improved performance on several tasks. PMID:10671904

A review of the literature on the effects of low doses of alcohol on driving-related skills

DOT National Transportation Integrated Search

2000-04-01

A review of the scientific literature regarding the effects of alcohol on driving-related skills was conducted. The review covered 112 articles dated from 1981 to 1997. Results were indexed by blood alcohol concentration (BAC) and behavioral area and...

Effects of relationship motivation, partner familiarity, and alcohol on women's risky sexual decision making.

PubMed

Zawacki, Tina; Norris, Jeanette; Hessler, Danielle M; Morrison, Diane M; Stoner, Susan A; George, William H; Davis, Kelly Cue; Abdallah, Devon A

2009-06-01

This experiment examined the effects of women's relationship motivation, partner familiarity, and alcohol consumption on sexual decision making. Women completed an individual difference measure of relationship motivation and then were randomly assigned to partner familiarity condition (low, high) and to alcohol consumption condition (high dose, low dose, no alcohol, placebo). Then women read and projected themselves into a scenario of a sexual encounter. Relationship motivation and partner familiarity interacted with intoxication to influence primary appraisals of relationship potential. Participants' primary and secondary relationship appraisals mediated the effects of women's relationship motivation, partner familiarity, and intoxication on condom negotiation, sexual decision abdication, and unprotected sex intentions. These findings support a cognitive mediation model of women's sexual decision making and identify how individual and situational factors interact to shape alcohol's influences on cognitive appraisals that lead to risky sexual decisions. This knowledge can inform empirically based risky sex interventions.

Alcohol and liver disease in Europe--Simple measures have the potential to prevent tens of thousands of premature deaths.

PubMed

Sheron, Nick

2016-04-01

In the World Health Organisation European Region, more than 2,370,000 years of life are lost from liver disease before the age of 50; more than lung cancer, trachea, bronchus, oesophageal, stomach, colon, rectum and pancreatic cancer combined. Between 60-80% of these deaths are alcohol related, a disease for which no pharmaceutical therapy has yet been shown to improve long-term survival. The toxicity of alcohol is dose related at an individual level, and is dose related at a population level; overall liver mortality is largely determined by population alcohol consumption. Trends in alcohol consumption correlate closely with trends in overall liver mortality, with 3-5-fold decreases or increases in liver mortality in different European countries over the last few decades. The evidence base for alcohol control measures aimed at reducing population alcohol consumption has been subjected to rigorous evaluation; most recently by the Organisation for Economic Co-Operation and Development (OECD). Effective alcohol policy measures reduce alcohol mortality, including mortality from liver disease. The most effective and cost effective measures have been summarised by the OECD and the World Health Organisation: regular incremental above inflation tax increases, a minimum price for alcohol, effective protection of children from alcohol marketing and low level interventions from clinicians. Simple, cheap and effective changes to alcohol policy by European Institutions and member states have the potential to dramatically reduce liver mortality in Europe. Copyright © 2016. Published by Elsevier B.V.

High dose lycopene supplementation increases hepatic cytochrome P4502E1 protein and inflammation in alcohol-fed rats.

PubMed

Veeramachaneni, Sudipta; Ausman, Lynne M; Choi, Sang Woon; Russell, Robert M; Wang, Xiang-Dong

2008-07-01

Recent in vitro evidence suggests that the antioxidant lycopene can prevent alcohol-induced oxidative stress and inflammation. However, knowledge of possible interactions in vivo between escalating doses of lycopene and chronic alcohol ingestion are lacking. In this study, we investigated potential interactions between alcohol ingestion and lycopene supplementation and their effect on hepatic lycopene concentration, cytochrome P4502E1 (CYP2E1) induction, and inflammation. Fischer 344 rats (6 groups, n = 10 per group) were fed either a liquid ethanol Lieber-DeCarli diet or a control diet (isocaloric maltodextrin substituted for ethanol) with or without lycopene supplementation at 2 doses (1.1 or 3.3 mg x kg body weight(-1) x d(-1)) for 11 wk. Plasma and hepatic concentrations of lycopene isomers were assessed by HPLC analysis. We examined expressions of hepatic CYP2E1 and tumor necrosis factor-alpha (TNFalpha) and the incidence of hepatic inflammatory foci. Both plasma and hepatic lycopene concentrations were greater in alcohol-fed rats than in control rats supplemented with identical doses of lycopene. In contrast, alcohol-fed rats had a lower percentage of lycopene cis isomers in the plasma and the liver compared with control rats fed the same dose of lycopene. Notably, lycopene supplementation at the higher dose significantly induced hepatic CYP2E1 protein, TNFalpha mRNA, and the incidence of inflammatory foci in the alcohol-fed rats but not in the control rats. These data indicate an interaction between chronic alcohol ingestion and lycopene supplementation and suggest a need for caution among individuals consuming high amounts of both alcohol and lycopene.

Acute Effect of Alcohol Intake on Cardiovascular Autonomic Regulation During the First Hours of Sleep in a Large Real-World Sample of Finnish Employees: Observational Study

PubMed Central

Helander, Elina; Korhonen, Ilkka; Myllymäki, Tero; Kujala, Urho M; Lindholm, Harri

2018-01-01

Background Sleep is fundamental for good health, and poor sleep has been associated with negative health outcomes. Alcohol consumption is a universal health behavior associated with poor sleep. In controlled laboratory studies, alcohol intake has been shown to alter physiology and disturb sleep homeostasis and architecture. The association between acute alcohol intake and physiological changes has not yet been studied in noncontrolled real-world settings. Objective The aim of this study was to assess the effects of alcohol intake on the autonomic nervous system (ANS) during sleep in a large noncontrolled sample of Finnish employees. Methods From a larger cohort, this study included 4098 subjects (55.81%, 2287/4098 females; mean age 45.1 years) who had continuous beat-to-beat R-R interval recordings of good quality for at least 1 day with and for at least 1 day without alcohol intake. The participants underwent continuous beat-to-beat R-R interval recording during their normal everyday life and self-reported their alcohol intake as doses for each day. Heart rate (HR), HR variability (HRV), and HRV-derived indices of physiological state from the first 3 hours of sleep were used as outcomes. Within-subject analyses were conducted in a repeated measures manner by studying the differences in the outcomes between each participant’s days with and without alcohol intake. For repeated measures two-way analysis of variance, the participants were divided into three groups: low (≤0.25 g/kg), moderate (>0.25-0.75 g/kg), and high (>0.75 g/kg) intake of pure alcohol. Moreover, linear models studied the differences in outcomes with respect to the amount of alcohol intake and the participant’s background parameters (age; gender; body mass index, BMI; physical activity, PA; and baseline sleep HR). Results Alcohol intake was dose-dependently associated with increased sympathetic regulation, decreased parasympathetic regulation, and insufficient recovery. In addition to moderate and high alcohol doses, the intraindividual effects of alcohol intake on the ANS regulation were observed also with low alcohol intake (all P<.001). For example, HRV-derived physiological recovery state decreased on average by 9.3, 24.0, and 39.2 percentage units with low, moderate, and high alcohol intake, respectively. The effects of alcohol in suppressing recovery were similar for both genders and for physically active and sedentary subjects but stronger among young than older subjects and for participants with lower baseline sleep HR than with higher baseline sleep HR. Conclusions Alcohol intake disturbs cardiovascular relaxation during sleep in a dose-dependent manner in both genders. Regular PA or young age do not protect from these effects of alcohol. In health promotion, wearable HR monitoring and HRV-based analysis of recovery might be used to demonstrate the effects of alcohol on sleep on an individual level. PMID:29549064

Drink and Think: Impact of Alcohol on Cognitive Functions and Dementia - Evidence of Dose-Related Effects.

PubMed

Gutwinski, Stefan; Schreiter, Stefanie; Priller, Josef; Henssler, Jonathan; Wiers, Corinde E; Heinz, Andreas

2017-09-26

Regular alcohol consumption affects cognitive performance and the development of dementia. So far, findings are contradicting, which might be explained in part by dose-related effects. For this narrative review, we undertook a literature search for surveys investigating the impact of alcohol consumption on cognitive performance and the development of dementia. The majority of studies observed a U-shaped relationship between regular alcohol consumption and cognitive function: frequent heavy consumption of alcohol alters brain functions and decreases cognitive performance; regular light and moderate consumption may have protective impact. In many studies, total abstainers show an inferior cognitive performance than people with moderate or light consumption. Nevertheless, policy implications are difficult to draw for at least 2 reasons: (1) the possible risks associated with alcohol consumption and (2) the potential confounders in the group of non-consumers and heavy consumers. © Georg Thieme Verlag KG Stuttgart · New York.

[Comparative study on promoting blood effects of Danshen-Honghua herb pair with different preparations based on chemometrics and multi-attribute comprehensive index methods].

PubMed

Qu, Cheng; Tang, Yu-Ping; Shi, Xu-Qin; Zhou, Gui-Sheng; Shang, Er-Xin; Shang, Li-Li; Guo, Jian-Ming; Liu, Pei; Zhao, Jing; Zhao, Bu-Chang; Duan, Jin-Ao

2017-08-01

To evaluate the promoting blood circulation and removing blood stasis effects of Danshen-Honghua(DH) herb pair with different preparations (alcohol, 50% alcohol and water) on blood rheology and coagulation functions in acute blood stasis rats, and optimize the best preparation method of DH based on principal component analysis(PCA), hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods. Ice water bath and subcutaneous injection of adrenaline were both used to establish the acute blood stasis rat model. Then the blood stasis rats were administrated intragastrically with DH (alcohol, 50% alcohol and water) extracts. The whole blood viscosity(WBV), plasma viscosity(PV), erythrocyte sedimentation rate(ESR) and haematocrit(HCT) were tested to observe the effects of DH herb pair with different preparations and doses on hemorheology of blood stasis rats; the activated partial thromboplastin time(APTT), thrombin time(TT), prothrombin time(PT), and plasma fibrinogen(FIB) were tested to observe the effects of DH herb pair with different preparations on blood coagulation function and platelet aggregation of blood stasis rats. Then PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods were all used to comprehensively evaluate the total promoting blood circulation and removing blood stasis effects of DH herb pair with different preparations. The hemorheological indexes and coagulation parameters of model group had significant differences with normal blank group. As compared with the model group, the DH herb pair with different preparations at low, middle and high doses could improve the blood hemorheology indexes and coagulation parameters in acute blood stasis rats with dose-effect relation. Based on the PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods, the high dose group of 50% alcohol extract had the best effect of promoting blood circulation and removing blood stasis. Under the same dose but different preparations, 50% alcohol DH could obviously improve the hemorheology and blood coagulation function in acute blood stasis rats. These results suggested that DH herb pair with different preparations could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats, and the optimized preparation of DH herb pair on promoting blood effects was 50% alcohol extract, providing scientific basis for more effective application of the DH herb pair in modern clinic medicine. Copyright© by the Chinese Pharmaceutical Association.

COMPARISON OF IN VIVO AND IN VITRO METHODS FOR ASSESSING EFFECTS OF ALLYL ALCOHOL ON THE LIVER

EPA Science Inventory

Allyl alcohol was administered to female Fischer 344 rats at doses of 0, 3, 10 and 30 mg/kg daily for 7 days. Plasma sorbitol dehydrogenase was minimally elevated. No dose related changes were observed in hexobarbital oxidation, aniline hydroxylation, or ethylmorphine demethylati...

The effect of cannabis compared with alcohol on driving.

PubMed

Sewell, R Andrew; Poling, James; Sofuoglu, Mehmet

2009-01-01

The prevalence of both alcohol and cannabis use and the high morbidity associated with motor vehicle crashes has lead to a plethora of research on the link between the two. Drunk drivers are involved in 25% of motor vehicle fatalities, and many accidents involve drivers who test positive for cannabis. Cannabis and alcohol acutely impair several driving-related skills in a dose-related fashion, but the effects of cannabis vary more between individuals than they do with alcohol because of tolerance, differences in smoking technique, and different absorptions of Delta(9)-tetrahydrocannabinol (THC), the active ingredient in marijuana. Detrimental effects of cannabis use vary in a dose-related fashion, and are more pronounced with highly automatic driving functions than with more complex tasks that require conscious control, whereas alcohol produces an opposite pattern of impairment. Because of both this and an increased awareness that they are impaired, marijuana smokers tend to compensate effectively while driving by utilizing a variety of behavioral strategies. Combining marijuana with alcohol eliminates the ability to use such strategies effectively, however, and results in impairment even at doses which would be insignificant were they of either drug alone. Epidemiological studies have been inconclusive regarding whether cannabis use causes an increased risk of accidents; in contrast, unanimity exists that alcohol use increases crash risk. Furthermore, the risk from driving under the influence of both alcohol and cannabis is greater than the risk of driving under the influence of either alone. Future research should focus on resolving contradictions posed by previous studies, and patients who smoke cannabis should be counseled to wait several hours before driving, and avoid combining the two drugs.

The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

PubMed

Li, Xiang; Li, Xu; Li, Yi-Xiang; Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

2015-01-01

We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish

PubMed Central

Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

2015-01-01

We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an “inverted V” dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure. PMID:26558894

Processing of facial affect in social drinkers: a dose-response study of alcohol using dynamic emotion expressions.

PubMed

Kamboj, Sunjeev K; Joye, Alyssa; Bisby, James A; Das, Ravi K; Platt, Bradley; Curran, H Valerie

2013-05-01

Studies of affect recognition can inform our understanding of the interpersonal effects of alcohol and help develop a more complete neuropsychological profile of this drug. The objective of the study was to examine affect recognition in social drinkers using a novel dynamic affect-recognition task, sampling performance across a range of evolutionarily significant target emotions and neutral expressions. Participants received 0, 0.4 or 0.8 g/kg alcohol in a double-blind, independent groups design. Relatively naturalistic changes in facial expression-from neutral (mouth open) to increasing intensities of target emotions, as well as neutral (mouth closed)-were simulated using computer-generated dynamic morphs. Accuracy and reaction time were measured and a two-high-threshold model applied to hits and false-alarm data to determine sensitivity and response bias. While there was no effect on the principal emotion expressions (happiness, sadness, fear, anger and disgust), compared to those receiving 0.8 g/kg of alcohol and placebo, participants administered with 0.4 g/kg alcohol tended to show an enhanced response bias to neutral expressions. Exploration of this effect suggested an accompanying tendency to misattribute neutrality to sad expressions following the 0.4-g/kg dose. The 0.4-g/kg alcohol-but not 0.8 g/kg-produced a limited and specific modification in affect recognition evidenced by a neutral response bias and possibly an accompanying tendency to misclassify sad expressions as neutral. In light of previous findings on involuntary negative memory following the 0.4-g/kg dose, we suggest that moderate-but not high-doses of alcohol have a special relevance to emotional processing in social drinkers.

Effects of alcohol on attention orienting and dual-task performance during simulated driving: an event-related potential study.

PubMed

Wester, Anne E; Verster, Joris C; Volkerts, Edmund R; Böcker, Koen B E; Kenemans, J Leon

2010-09-01

Driving is a complex task and is susceptible to inattention and distraction. Moreover, alcohol has a detrimental effect on driving performance, possibly due to alcohol-induced attention deficits. The aim of the present study was to assess the effects of alcohol on simulated driving performance and attention orienting and allocation, as assessed by event-related potentials (ERPs). Thirty-two participants completed two test runs in the Divided Attention Steering Simulator (DASS) with blood alcohol concentrations (BACs) of 0.00%, 0.02%, 0.05%, 0.08% and 0.10%. Sixteen participants performed the second DASS test run with a passive auditory oddball to assess alcohol effects on involuntary attention shifting. Sixteen other participants performed the second DASS test run with an active auditory oddball to assess alcohol effects on dual-task performance and active attention allocation. Dose-dependent impairments were found for reaction times, the number of misses and steering error, even more so in dual-task conditions, especially in the active oddball group. ERP amplitudes to novel irrelevant events were also attenuated in a dose-dependent manner. The P3b amplitude to deviant target stimuli decreased with blood alcohol concentration only in the dual-task condition. It is concluded that alcohol increases distractibility and interference from secondary task stimuli, as well as reduces attentional capacity and dual-task integrality.

Rape-Myth Congruent Beliefs in Women Resulting from Exposure to Violent Pornography: Effects of Alcohol and Sexual Arousal

ERIC Educational Resources Information Center

Davis, Kelly Cue; Norris, Jeanette; George, William H.; Martell, Joel; Heiman, Julia R.

2006-01-01

Previous research findings indicate that women suffer a variety of detrimental effects from exposure to violent pornography. This study used an experimental paradigm to examine the effects of a moderate alcohol dose and alcohol expectancies on women's acute reactions to a violent pornographic stimulus. A community sample of female social drinkers…

Binge drinking in undergraduates: relationships with sex, drinking behaviors, impulsivity, and the perceived effects of alcohol.

PubMed

Balodis, Iris M; Potenza, Marc N; Olmstead, Mary C

2009-09-01

Binge drinking on university campuses is associated with social and health-related problems. To determine the factors that may predict this behavior, we collected information on alcohol use, alcohol expectations, and impulsivity from 428 undergraduate students attending a Canadian university. The subjective effects of a binge drinking dose of alcohol were assessed in a subset of participants. In the larger sample, 72% of students reported drinking at or above binge drinking thresholds on a regular basis. Men reported alcohol consumption per drinking occasion, which was consistent with other studies, but the frequency of drinking occasions among women was higher than in earlier studies, suggesting that consumption in women may be increasing. Compared with men, women reported different expectations of alcohol, specifically related to sociability and sexuality. Self-reported impulsivity scores were related, albeit weakly, to drinking behaviors and to expectations in both the sexes. Finally, intoxicated binge drinkers reported feeling less intoxicated, liking the effects more, and wanting more alcohol than did non-binge drinkers receiving an equivalent dose of alcohol. These results have implications for sex-specific prevention strategies for binge drinking on university campuses.

Analysis of liver damage from radon, X-ray, or alcohol treatments in mice using a self-organizing map.

PubMed

Kanzaki, Norie; Kataoka, Takahiro; Etani, Reo; Sasaoka, Kaori; Kanagawa, Akihiro; Yamaoka, Kiyonori

2017-01-01

In our previous studies, we found that low-dose radiation inhibits oxidative stress-induced diseases due to increased antioxidants. Although these effects of low-dose radiation were demonstrated, further research was needed to clarify the effects. However, the analysis of oxidative stress is challenging, especially that of low levels of oxidative stress, because antioxidative substances are intricately involved. Thus, we proposed an approach for analysing oxidative liver damage via use of a self-organizing map (SOM)-a novel and comprehensive technique for evaluating hepatic and antioxidative function. Mice were treated with radon inhalation, irradiated with X-rays, or subjected to intraperitoneal injection of alcohol. We evaluated the oxidative damage levels in the liver from the SOM results for hepatic function and antioxidative substances. The results showed that the effects of low-dose irradiation (radon inhalation at a concentration of up to 2000 Bq/m 3 , or X-irradiation at a dose of up to 2.0 Gy) were comparable with the effect of alcohol administration at 0.5 g/kg bodyweight. Analysis using the SOM to discriminate small changes was made possible by its ability to 'learn' to adapt to unexpected changes. Moreover, when using a spherical SOM, the method comprehensively examined liver damage by radon, X-ray, and alcohol. We found that the types of liver damage caused by radon, X-rays, and alcohol have different characteristics. Therefore, our approaches would be useful as a method for evaluating oxidative liver damage caused by radon, X-rays and alcohol. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

High-dose alcohol intoxication differentially modulates cognitive subprocesses involved in response inhibition.

PubMed

Stock, Ann-Kathrin; Schulz, Tom; Lenhardt, Martin; Blaszkewicz, Meinolf; Beste, Christian

2016-01-01

Aside from well-known physiological effects, high-dose alcohol intoxication (a.k.a. binge drinking) can lead to aversive social and legal consequences because response inhibition is usually compromised under the influence of alcohol. Although the behavioral aspects of this phenomenon were reported on extensively, the underlying neurophysiological mechanisms mediating this disinhibition are unclear. To close this gap, we used both behavioral and neurophysiological measures (event-related potentials, ERPs) to investigate which subprocesses of response inhibition are altered under the influence of high-dose alcohol intoxication. Using a within-subject design, we asked young healthy participants (n = 27) to complete a GO/NOGO task once sober and once intoxicated (approximately 1.2‰). During intoxication, high-dose alcohol effects were highest in a condition where the participants could not rely on automated stimulus-response mapping processes during response inhibition. In this context, the NOGO-P3 (ERP), that likely depends on dopaminergic signaling within mesocorticolimbic pathways and is thought to reflect motor inhibition and/or the evaluation of inhibitory processes, was altered in the intoxicated state. In contrast to this, the N2 component, which largely depends on nigrostriatal dopamine pathways and is thought to reflect inhibition on a pre-motor level, was not altered. Based on these results, we demonstrate that alcohol-induced changes of dopaminergic neurotransmission do not exert a global effect on response inhibition. Instead, changes are highly subprocess-specific and seem to mainly target mesocorticolimbic pathways that contribute to motor inhibition and the evaluation of such. © 2014 Society for the Study of Addiction.

Effects of desloratadine and alcohol coadministration on psychomotor performance.

PubMed

Scharf, Martin; Berkowitz, David

2007-02-01

This study was set up to evaluate the effects of desloratadine 7.5 mg daily, with and without alcohol, on sedation and psychomotor performance. In a double-blind, placebo-controlled, four-way crossover trial, 25 adult patients were randomized to desloratadine 7.5 mg, desloratadine 7.5 mg plus alcohol, placebo, or placebo plus alcohol. Alcohol was weight adjusted to an average blood alcohol concentration of 0.1%. Assessments included the modified Romberg test, Stanford Sleepiness Scale, Digit Symbol Substitution Test, Serial Add Subtract Reaction Time Test, and the Psychomotor Vigilance Test. The primary variable was the mean score of each of the five tests averaged over the treatment period, expressed as the mean percent change from baseline. Across these assessments, differences between desloratadine alone or with alcohol versus placebo alone or without alcohol, were not significant, whereas most differences between desloratadine and placebo alone versus desloratadine and placebo with alcohol were significant (p < 0.01). Thus, with or without alcohol, desloratadine 7.5 mg does not increase sedation or impair psychomotor performance. Most adverse events (AEs) were mild-to-moderate in severity, with the most frequently reported individual AEs being headache, fatigue, nausea, vomiting, and dry mouth. The study does have potential limitations. The measures used are restricted to a particular profile of the known effects of alcohol only, and the relatively high doses of alcohol used alone demonstrate effects on psychomotor function and attention. A single dose of desloratadine does not potentiate alcohol-mediated CNS impairment. Desloratadine alone or in combination with alcohol was safe and well tolerated.

Differential response to alcohol in light and moderate female social drinkers.

PubMed

Evans, S M; Levin, F R

2004-05-01

Individuals who are moderate drinkers are at increased risk to abuse alcohol. Moreover, women are more vulnerable than men to the adverse consequences of alcohol consumption and recent data indicate that the drinking pattern in women is becoming more similar to that of men. However, few studies have determined whether female moderate drinkers (MD) show a differential response to the subjective and performance effects of alcohol, compared to female light drinkers (LD). Fifteen female MD who consumed an average of 34.7 drinks/month were compared to 15 female LD who consumed an average of 6.7 drinks/month. None of the participants had a first-degree family history of alcoholism or substance abuse. The acute effects of alcohol (0, 0.25, 0.50, 0.75 mg/kg) were evaluated using a double-blind, placebo-controlled outpatient design. Drug effects were assessed using a full range of performance measures, subjective-effects questionnaires and observer ratings. Alcohol impaired performance in a dose-related manner on all performance tasks for both groups of females. However, MD were less impaired than LD on balance and Digit Symbol Substitution Test (DSST). This reduced response was also evident from the observer ratings, with MD being viewed as less impaired by alcohol than LD. While ratings of Drug Liking increased in both groups of women on the ascending limb of the breath alcohol curve, alcohol was disliked by LD on the descending limb and LD reported increased ratings of Bad Drug Effects following the high dose of alcohol. The reduced performance impairment, coupled with the positive subjective effects and relative absence of adverse subjective effects, suggestive of behavioral tolerance, could result in a progression towards increased alcohol consumption among moderate female social drinkers.

Lorcaserin, a selective 5-HT(2C) receptor agonist, decreases alcohol intake in female alcohol preferring rats.

PubMed

Rezvani, Amir H; Cauley, Marty C; Levin, Edward D

2014-10-01

Serotonergic systems in the brain have been found to be important in the addiction to alcohol. The purpose of this study was to evaluate the efficacy of a novel 5-HT2c receptor agonist, lorcaserin for reducing alcohol consumption in alcohol-preferring (P) rats. Adult female rats were allowed to drink water or alcohol (12%, v/v) using a standard two-bottle choice procedure. Once stable baselines were established, the acute (0, 0.3125, 0.625 and 1.25 mg/kg, s.c.), and chronic (0, 0.625 mg/kg, sc for 10 days) effects of lorcaserin on alcohol intake and preference were assessed at different time points. In a separate experiment, the effects of lorcaserin on locomotor activity were determined. Our results show that both 0.625 and 1.25 mg/kg lorcaserin significantly reduced alcohol intake at 2, 4 and 6 h. after the drug administration. The chronic administration of 0.625 mg/kg lorcaserin significantly reduced alcohol intake up to 6h every day after the injection and there was no sign of diminished efficacy of the drug during 10-day treatment. To determine the effects of lorcaserin on sucrose intake, rats were put on a two-bottle choice of water vs a solution of 7% sucrose. The high dose of lorcaserin (1.25 mg/kg, s.c.) reduced sucrose intake only for up to 2 h. When tested for locomotor activity, lorcaserin injected 20 min before testing significantly reduced locomotor activity at all doses. However, when it was injected 5.5h before the start of the 1-h session, neither dose had a significant effect on locomotor activity. These results show the efficacy of lorcaserin in reducing alcohol intake without a significant effect on water intake and locomotion suggesting the involvement of 5-HT2c receptors in alcohol seeking behavior. Further research is warranted to determine the possible efficacy of lorcaserin or similar drugs as treatments for the treatment of alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

Defining unnecessary disinfection procedures for single-dose and multiple-dose vials.

PubMed

Buckley, T; Dudley, S M; Donowitz, L G

1994-11-01

Recommendations in the literature conflict on the necessity of disinfecting single-use vials prior to aspiration of fluid. Interventions to disinfect the stopper surface on multiple-dose vials vary considerably. To determine the necessity of alcohol disinfection of the stopper on single-dose vials and to compare povidone-iodine and alcohol versus alcohol-only disinfection of the stopper prior to each needle penetration on multiple-dose vials. The rubber stopper surfaces of 100 single-dose vials were cultured for the presence of bacteria. To determine the efficacy of two procedures for disinfection of multiple-dose vials, 87 stopper surfaces routinely disinfected with both povidone-iodine and alcohol were cultured for bacteria. After a change in practice, 100 multiple-dose vials routinely disinfected with alcohol only were cultured for the presence of bacteria. Of the cultures done on single-dose vial stoppers, 99% were sterile. A comparison of the two disinfection techniques for multiple-dose vials revealed that 83 (95%) of the 87 vials prepped with both povidone-iodine and alcohol were sterile, compared with all stoppers disinfected with alcohol only. This study shows the lack of necessity of any disinfection procedure on the rubber stopper of single-dose vials and the efficacy of alcohol only for disinfecting the stopper of multiple-dose vials.

R(+)-Baclofen, but Not S(-)-Baclofen, Alters Alcohol Self-Administration in Alcohol-Preferring Rats.

PubMed

Lorrai, Irene; Maccioni, Paola; Gessa, Gian Luigi; Colombo, Giancarlo

2016-01-01

Racemic baclofen [(±)-baclofen] has repeatedly been reported to suppress several -alcohol-motivated behaviors, including alcohol drinking and alcohol -self-administration, in rats and mice. Recent data suggested that baclofen may have bidirectional, stereospecific effects, with the more active enantiomer, R(+)-baclofen, suppressing alcohol intake and the less active enantiomer, S(-)-baclofen, stimulating alcohol intake in mice. The present study was designed to investigate whether this enantioselectivity of baclofen effects may also extend to the reinforcing properties of alcohol in rats. To this end, selectively bred Sardinian alcohol-preferring (sP) rats were initially trained to lever respond on a fixed ratio 4 (FR4) schedule of reinforcement for alcohol (15%, v/v) in daily 30-min sessions. Once responding had stabilized, rats were tested with vehicle, (±)-baclofen (3 mg/kg), R(+)-baclofen (0.75, 1.5, and 3 mg/kg), and S(-)-baclofen (6, 12, and 24 mg/kg) under the FR4 schedule of reinforcement. Treatment with 3 mg/kg (±)-baclofen reduced the number of lever responses for alcohol and estimated amount of self-administered alcohol by approximately 60% in comparison to vehicle treatment. R(+)-baclofen was approximately twice as active as (±)-baclofen: treatment with 1.5 mg/kg R(+)-baclofen decreased both variables to an extent similar to that of the decreasing effect of 3 mg/kg (±)-baclofen. Conversely, treatment with all doses of S(-)-baclofen failed to affect alcohol self administration. These results (a) confirm that non-sedative doses of (±)-baclofen effectively suppressed the reinforcing properties of alcohol in sP rats and (b) apparently do not extend to operant alcohol self-administration in sP rats the capability of S(-)-baclofen to stimulate alcohol drinking in mice.

Acute Effect of Alcohol Intake on Cardiovascular Autonomic Regulation During the First Hours of Sleep in a Large Real-World Sample of Finnish Employees: Observational Study.

PubMed

Pietilä, Julia; Helander, Elina; Korhonen, Ilkka; Myllymäki, Tero; Kujala, Urho M; Lindholm, Harri

2018-03-16

Sleep is fundamental for good health, and poor sleep has been associated with negative health outcomes. Alcohol consumption is a universal health behavior associated with poor sleep. In controlled laboratory studies, alcohol intake has been shown to alter physiology and disturb sleep homeostasis and architecture. The association between acute alcohol intake and physiological changes has not yet been studied in noncontrolled real-world settings. The aim of this study was to assess the effects of alcohol intake on the autonomic nervous system (ANS) during sleep in a large noncontrolled sample of Finnish employees. From a larger cohort, this study included 4098 subjects (55.81%, 2287/4098 females; mean age 45.1 years) who had continuous beat-to-beat R-R interval recordings of good quality for at least 1 day with and for at least 1 day without alcohol intake. The participants underwent continuous beat-to-beat R-R interval recording during their normal everyday life and self-reported their alcohol intake as doses for each day. Heart rate (HR), HR variability (HRV), and HRV-derived indices of physiological state from the first 3 hours of sleep were used as outcomes. Within-subject analyses were conducted in a repeated measures manner by studying the differences in the outcomes between each participant's days with and without alcohol intake. For repeated measures two-way analysis of variance, the participants were divided into three groups: low (≤0.25 g/kg), moderate (>0.25-0.75 g/kg), and high (>0.75 g/kg) intake of pure alcohol. Moreover, linear models studied the differences in outcomes with respect to the amount of alcohol intake and the participant's background parameters (age; gender; body mass index, BMI; physical activity, PA; and baseline sleep HR). Alcohol intake was dose-dependently associated with increased sympathetic regulation, decreased parasympathetic regulation, and insufficient recovery. In addition to moderate and high alcohol doses, the intraindividual effects of alcohol intake on the ANS regulation were observed also with low alcohol intake (all P<.001). For example, HRV-derived physiological recovery state decreased on average by 9.3, 24.0, and 39.2 percentage units with low, moderate, and high alcohol intake, respectively. The effects of alcohol in suppressing recovery were similar for both genders and for physically active and sedentary subjects but stronger among young than older subjects and for participants with lower baseline sleep HR than with higher baseline sleep HR. Alcohol intake disturbs cardiovascular relaxation during sleep in a dose-dependent manner in both genders. Regular PA or young age do not protect from these effects of alcohol. In health promotion, wearable HR monitoring and HRV-based analysis of recovery might be used to demonstrate the effects of alcohol on sleep on an individual level. ©Julia Pietilä, Elina Helander, Ilkka Korhonen, Tero Myllymäki, Urho M Kujala, Harri Lindholm. Originally published in JMIR Mental Health (http://mental.jmir.org), 16.03.2018.

Acute Alcohol Effects on Attentional Bias in Heavy and Moderate Drinkers

PubMed Central

Weafer, Jessica; Fillmore, Mark T.

2012-01-01

Heavy drinkers show an increased attentional bias to alcohol-related stimuli compared to moderate drinkers, and this bias is thought to promote motivation for alcohol consumption (Field & Cox, 2008). Studies have begun to examine acute alcohol effects on attentional bias, however little is known regarding how these effects might differ based on drinker type. Further, the degree to which attentional bias in response to alcohol is associated with excessive alcohol consumption remains unexplored. For the current study, 20 heavy drinkers and 20 moderate drinkers completed a visual probe task in response to placebo and two active doses of alcohol (0.45 g/kg and 0.65 g/kg). Participants’ eye-movements were monitored and attentional bias was calculated as the difference in time spent focused on alcohol compared to neutral images. Participants’ alcohol consumption was assessed by a timeline follow-back calendar and a laboratory ad lib consumption task. Results showed that heavy drinkers displayed significantly greater attentional bias than did moderate drinkers following placebo. However, heavy drinkers displayed a dose-dependent decrease in attentional bias following alcohol, whereas the drug had no effect in moderate drinkers. Individual differences in attentional bias under placebo were strongly associated with both self-reported and laboratory alcohol consumption, yet bias following alcohol administration did not predict either measure of consumption. These findings suggest that attentional bias is strongest before a drinking episode begins. As such, an attentional bias might be most influential in terms of initiation of alcohol consumption, and less of a factor in promoting continued consumption within the drinking episode. PMID:22732051

Alcohol, Drugs and Driving: Implications for Evaluating Driver Impairment

PubMed Central

Brown, Timothy; Milavetz, Gary; Murry, Daryl J.

2013-01-01

Impaired driving is a significant traffic safety problem, and alcohol and drugs taken before driving contribute substantially to this problem. With the increase in use of prescription medication and the decriminalization of some drugs, it has become increasingly important to understand the manifestation of driver impairment. Building upon previous alcohol research conducted at the National Advanced Driving Simulator (NADS), this study enrolled commercial bus drivers to evaluate the effect of triazolam on driving performance to assess difference between placebo, 0.125, and 0.25 mg doses in a randomized and double-blind design. On each of three randomized visits, subjects drove a simulator scenario that had previously been used to demonstrate effects of alcohol on driving performance. Plasma triazolam levels were obtained before the simulator drive. The protocol included participants receiving study medication and placebo over a 3-week period of time one to two weeks apart. The simulator drives used for this analysis occurred approximately 140 minutes after dosing—after the subjects had completed four bus simulator drives and neuropsychological tests over a 2-hour period of time surrounding dosing. The driving scenario contained representative situations on three types of roadways (urban, freeway, and rural) under nighttime driving conditions. Lane keeping performance (ability to drive straight in the lane) under the three doses of triazolam demonstrates that at the 0.25 mg dose, statistically significant effects on performance are observed, but no effects are found at the 0.125 mg level when testing at this time period after dosing. This differs from the effects of alcohol, which shows impairing effects at a 0.05% blood alcohol concentration (BAC) and a greater effect at 0.10% BAC. These results demonstrate the importance of understanding how different types of drugs affect driving performance in realistic driving environments. Although some compounds may have an effect that correlates linearly to dosage, that is not always the case. An understanding of these differences and how they vary across driving tasks is essential to developing a robust evaluation protocol that can accurately describe the effects of a wide variety of drugs on driver impairment. This information can be used to reduce the risk of deleterious effects of therapeutic medications while ensuring their safe and beneficial use. PMID:24406943

Oral metformin-ascorbic acid co-administration ameliorates alcohol-induced hepatotoxicity in rats.

PubMed

Adeneye, A A; Benebo, A S

2007-01-01

Alcoholic liver disease remains a major cause of liver failure worldwide with no available curative or prophylactic therapy as at present. High dose metformin is reported to ameliorate liver injuries in both human and animal models of acute and chronic alcoholic liver injuries. The aim of the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure. In the present study, ameliorating effect of 200 mg/ kg/day of ascorbic acid (Asc), 500 mg/kg/day of metformin (Met) and their co-administration (Met-Asc) were investigated in 5 groups of 50% ethanol-treated male Wistar rats for 2 weeks of the experiment. The body weight of each rat was taken on days 1, 7, and 14 of the experiment, respectively. On day 15, fasted blood samples for plasma lipids and liver enzyme markers were collected via cardiac puncture from the rats under diethyl ether anaesthesia. Results showed that administration of graded oral doses of 50% ethanol for 14 days significantly (p<0.001) elevated the plasma liver enzymes--aspartate aminotransferase (AST), alanine aminotansferase (ALT) and alkaline phosphatase (ALP). Two weeks of ethanol treatment also induced alterations in the plasma triglycerides (PTG), total cholesterol (PTC), high density lipoprotein (HDL-c), and low density lipoprotein (LDL-c). However, these elevations were significantly (p<0.05) attenuated by Asc, Met, and Met-Asc after 14 days of oral treatment, with Met-Asc having higher significant (p<0.001) ameliorating effect than Asc alone but with comparative effect to that of Met alone. High dose metformin-ascorbic acid co-administration protected the liver against the deleterious effects of chronic high dose alcohol and the hepatoprotective effect of Met-Asc appeared to be due mainly to the metformin molecule of the drug combination. However, further studies would be required to evaluate the mechanisms underlying the observed effects.

Driving while drinking: performance impairments resulting from social drinking.

PubMed

Charlton, Samuel G; Starkey, Nicola J

2015-01-01

Previous research has shown that the effects of alcohol on drivers' performance can differ depending on whether blood alcohol concentrations are increasing or decreasing. The present research used a more ecologically representative alcohol consumption protocol in order to determine whether the same pattern of driver impairment would occur when drinking occurred in social groups over a longer period of time. Forty-four participants were assigned to one of two alcohol dose conditions or a placebo control group and consumed alcohol in groups of three (typically one participant from each condition) such that they gradually reached their target BAC (.05 or .08) and maintained it for 1 h. The participants completed a series of cognitive tests (Cogstate test battery) and a simulated driving task (driver attention inhibition and reaction test) over the course of their intoxication curve (approximately 4 h). The results showed strong placebo effects on ratings of subjective intoxication. Driving and cognitive performance both showed dose-dependent alcohol impairment, and some measures displayed acute protracted error. The findings provide strong evidence of expectancy effects in contributing to self-perceptions of intoxication. Copyright © 2014 Elsevier Ltd. All rights reserved.

Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice

PubMed Central

Farook, Justin M.; Krazem, Ali; Littleton, John M.; Barron, Susan

2008-01-01

In the present study, we examined the effects of acamprosate for its ability to reduce handling induced convulsions (HICs) during alcohol withdrawal. Diazepam was used as a positive control. Swiss Webster male mice received three daily IP injections of alcohol (2.5 g/kg) or alcohol (2.5 g/kg) + methylpyrazole (4-MP) (9 mg/kg). (4-MP, being an alcohol dehydrogenase inhibitor slows down the breakdown of alcohol. 4-MP in combination with alcohol exhibits a dramatic increase in blood alcohol level compared to alcohol alone). Ten hours following the last alcohol injection, the mice were picked up by the tail and examined for their seizure susceptibility (HICs). Diazepam, a benzodiazepine known to reduce seizures during alcohol withdrawal, significantly reduced these HICs at doses of 0.25, 0.5 and 1mg/kg (p’s < 0.001). Acamprosate, an anti-relapse compound used clinically in newly abstinent alcoholics, also reduced these HICs at doses of 100, 200 and 300mg/kg (p’s < 0.05). This study supports the use of acamprosate during periods of alcohol withdrawal as well as during abstinence. PMID:18577392

Gabapentin treatment for alcohol dependence: a randomized clinical trial.

PubMed

Mason, Barbara J; Quello, Susan; Goodell, Vivian; Shadan, Farhad; Kyle, Mark; Begovic, Adnan

2014-01-01

Approved medications for alcohol dependence are prescribed for less than 9% of US alcoholics. To determine if gabapentin, a widely prescribed generic calcium channel/γ-aminobutyric acid-modulating medication, increases rates of sustained abstinence and no heavy drinking and decreases alcohol-related insomnia, dysphoria, and craving, in a dose-dependent manner. A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women older than 18 years with current alcohol dependence, conducted from 2004 through 2010 at a single-site, outpatient clinical research facility adjoining a general medical hospital. Oral gabapentin (dosages of 0 [placebo], 900 mg, or 1800 mg/d) and concomitant manual-guided counseling. Rates of complete abstinence and no heavy drinking (coprimary) and changes in mood, sleep, and craving (secondary) over the 12-week study. RESULTS Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% (95% CI, 1.1%-13.7%) in the placebo group, 11.1% (95% CI, 5.2%-22.2%) in the 900-mg group, and 17.0% (95% CI, 8.9%-30.1%) in the 1800-mg group (P = .04 for linear dose effect; number needed to treat [NNT] = 8 for 1800 mg). The no heavy drinking rate was 22.5% (95% CI, 13.6%-37.2%) in the placebo group, 29.6% (95% CI, 19.1%-42.8%) in the 900-mg group, and 44.7% (95% CI, 31.4%-58.8%) in the 1800-mg group (P = .02 for linear dose effect; NNT = 5 for 1800 mg). Similar linear dose effects were obtained with measures of mood (F2 = 7.37; P = .001), sleep (F2 = 136; P < .001), and craving (F2 = 3.56; P = .03). There were no serious drug-related adverse events, and terminations owing to adverse events (9 of 150 participants), time in the study (mean [SD], 9.1 [3.8] weeks), and rate of study completion (85 of 150 participants) did not differ among groups. Gabapentin (particularly the 1800-mg dosage) was effective in treating alcohol dependence and relapse-related symptoms of insomnia, dysphoria, and craving, with a favorable safety profile. Increased implementation of pharmacological treatment of alcohol dependence in primary care may be a major benefit of gabapentin as a treatment option for alcohol dependence. clinicaltrials.gov Identifier: NCT00391716.

Comparative Evaluation of Partial α2 -Adrenoceptor Agonist and Pure α2 -Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice.

PubMed

Arora, Shivani; Vohora, Divya

2016-08-01

As an addictive drug, alcohol produces withdrawal symptoms if discontinued abruptly after chronic use. Clonidine (CLN), a partial α2 -adrenergic agonist, and mirtazapine (MRT), an antagonist of α2 -adrenoceptor, both clinically aid alcohol withdrawal. Considering different mechanisms of action of the two drugs, this study was designed to see how far these two mechanistically different drugs differ in their ability to decrease the severity of ethanol withdrawal syndrome. The effect of CLN and MRT on ethanol withdrawal-induced anxiety, depression and memory impairment was analysed using EPM, FST and PAR tests, respectively. Animals received distilled water, ethanol and/or either of the drugs (CLN and MRT) in different doses. Relapse to alcohol use was analysed by CPP test. Animals received ethanol as a conditioning drug and distilled water, CLN or MRT as test drug. CLN and MRT both alleviated anxiety in a dose-dependent manner. MRT (4 mg/kg) was more effective than CLN (0.1 mg/kg) in ameliorating the anxiogenic effect of alcohol withdrawal. However, CLN treatment increased depression. It significantly decreased swimming time and increased immobility time, whereas MRT treatment decreased immobility time and increased climbing and swimming time during abstinence. The effect was dose dependent for both drugs. The results of PAR test show that CLN treatment worsens working memory. Significant increase in SDE and TSZ and decrease in SDL were observed in CLN-treated animals. MRT treatment, on the other hand, improved working memory at both doses. Further, both CLN and MRT alleviated craving. A significant decrease in time spent in the ethanol-paired chamber was seen. MRT treatment at both doses showed better effect than CLN in preventing the development of preference in CPP test. These findings indicate a potential therapeutic use and better profile of mirtazapine over clonidine in improving memory, as well as in alleviating depression, anxiety and craving associated with alcohol withdrawal. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Effects of Varenicline Alone and in Combination With Low-dose Naltrexone on Alcohol-primed Smoking in Heavy-drinking Tobacco Users: A Preliminary Laboratory Study.

PubMed

Roberts, Walter; Shi, Julia M; Tetrault, Jeanette M; McKee, Sherry A

Heavy-drinking tobacco users are less likely to successfully quit smoking than their moderate-drinking counterparts, even when they are prescribed smoking cessation medication. One strategy for improving treatment outcomes in this subgroup of tobacco users may be to combine medication therapies to target both alcohol and tobacco use simultaneously. Adding naltrexone to frontline smoking cessation treatments may improve treatment outcomes in this group. This double-blind, placebo-controlled human laboratory study examined the effects of varenicline (2 mg/d) and varenicline (2 mg/d), combined with a low dose of naltrexone (25 mg/d) on alcohol-primed smoking behavior in a laboratory model of smoking relapse in heavy-drinking tobacco users (n = 30). Participants attended a laboratory session and received an alcohol challenge (target breath alcohol concentration = 0.030 g/dL). They completed a smoking delay task that assessed their ability to resist smoking followed by an ad libitum smoking phase (primary outcomes). They also provided ratings of subjective drug effects and craving, and carbon monoxide levels were measured after smoking (secondary outcomes). Participants receiving varenicline monotherapy delayed smoking longer and smoked fewer cigarettes than those on placebo. Participants receiving varenicline + low-dose naltrexone did not delay smoking longer than those receiving varenicline alone. Participants in both active medication arms smoked fewer cigarettes ad libitum than those receiving placebo. Varenicline can improve smoking outcomes even after an alcohol prime, supporting its use in heavy drinkers who wish to quit smoking. Findings did not support increased efficacy of combined varenicline + low-dose naltrexone relative to varenicline monotherapy.

A moderate dose of red wine, but not de-alcoholized red wine increases coronary flow reserve.

PubMed

Kiviniemi, Tuomas O; Saraste, Antti; Toikka, Jyri O; Saraste, Markku; Raitakari, Olli T; Pärkkä, Jussi P; Lehtimäki, Terho; Hartiala, Jaakko J; Viikari, Jorma; Koskenvuo, Juha W

2007-12-01

Red wine consumption is associated with reduced cardiovascular disease mortality. Its cardioprotective properties may be partly related to its ability to improve endothelial function. The purpose of this randomized controlled cross-over study was to determine whether moderate doses of red wine and de-alcoholized red wine improve coronary flow velocity reserve (CFR). Using transthoracic Doppler echocardiography, 176 CFR measurements were made in 22 healthy men before and after ingestion of a moderate (4.0+/-0.4 dl) and an escalating high dose (total amount 8.1+/-0.9 dl) of alcohol-containing red wine and de-alcoholized red wine, which contained similar amounts of phenolic substances. The difference in plasma antioxidant capacity was determined by colorimetric assay kit. Red wine increased CFR from 3.8+/-1.4 to 4.5+/-1.4 (p<0.01) and 4.0+/-1.2 (p=NS) after moderate and high doses, respectively; whereas de-alcoholized red wine had no significant effects on CFR (4.0+/-0.7, 4.3+/-1.3 and 4.5+/-1.4, respectively). Plasma antioxidant capacity increased significantly after high dose of red wine (27.5+/-14.7%, p<0.001), but not after de-alcoholized red wine (0.5+/-10.5%, p=NS) despite similar amounts of phenolic substances. Differences between CFR and plasma antioxidant capacities before and after drinking had no significant association. A moderate dose of red wine, but not de-alcoholized red wine increases CFR. The increase of CFR is probably mediated by other than direct antioxidant properties of polyphenols, because the simultaneous increase of CFR and plasma antioxidant capacity were not associated.

Chronic intracerebroventricular infusion of nociceptin/orphanin FQ increases food and ethanol intake in alcohol-preferring rats.

PubMed

Cifani, Carlo; Guerrini, Remo; Massi, Maurizio; Polidori, Carlo

2006-11-01

Central administration of low doses of nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid-like orphan receptor NOP, have been shown to reduce ethanol consumption, ethanol-induced conditioned place preference and stress-induced reinstatement of alcohol-seeking behavior in alcohol preferring rats. The present study evaluated the effect of continuous (7 days) lateral brain ventricle infusions of N/OFQ (0, 0.25, 1, 4, and 8 microg/h), by means of osmotic mini-pumps, on 10% ethanol intake in Marchigian-Sardinian alcohol-preferring (msP) rats provided 2h or 24h access to it. N/OFQ dose-dependently increased food intake in msP rats. On the other hand, in contrast to previous studies with acute injections, continuous lateral brain ventricle infusion of high doses of N/OFQ increased ethanol consumption when the ethanol solution was available for 24h/day or 2h/day. The present study demonstrates that continuous activation of the opioidergic N/OFQ receptor does not blunt the reinforcing effects of ethanol. Moreover, the data suggest that continuous activation of the opioidergic N/OFQ receptor is not a suitable way to reduce alcohol abuse.

Beer elicits vasculoprotective effects through Akt/eNOS activation.

PubMed

Vilahur, Gemma; Casani, Laura; Mendieta, Guiomar; Lamuela-Raventos, Rosa M; Estruch, Ramon; Badimon, Lina

2014-12-01

There is controversy regarding the effect of alcohol beverage intake in vascular vasodilatory function in peripheral arteries. The effects of beer intake in coronary vasodilation remain unknown. We investigated whether regular beer intake (alcohol and alcohol-free) protects against hypercholesterolaemia-induced coronary endothelial dysfunction and the mechanisms behind this effect. Pigs were fed 10 days: (i) a Western-type hypercholesterolaemic diet (WD); (ii) WD+low-dose beer (12·5 g alcohol/day); (iii) WD+moderate-dose beer (25 g alcohol/day); or (iv) WD+moderate-dose alcohol-free-beer (0·0 g alcohol/day). Coronary responses to endothelium-dependent vasoactive drugs (acetylcholine: receptor mediated; calcium ionophore-A23189: nonreceptor mediated), endothelium-independent vasoactive drug (SNP) and L-NMMA (NOS-antagonist) were evaluated in the LAD coronary artery by flow Doppler. Coronary Akt/eNOS activation, MCP-1 expression, oxidative DNA damage and superoxide production were assessed. Lipid profile, lipoproteins resistance to oxidation and urinary isoxanthohumol concentration were evaluated. Alcoholic and nonalcoholic beer intake prevented WD-induced impairment of receptor- and non-receptor-operated endothelial-dependent coronary vasodilation. All animals displayed a similar vasodilatory response to SNP and L-NMMA blunted all endothelial-dependent vasorelaxation responses. Haemodynamic parameters remained unchanged. Coronary arteries showed lower DNA damage and increased Akt/eNOS axis activation in beer-fed animals. Animals taking beer showed HDL with higher antioxidant capacity, higher LDL resistance to oxidation and increased isoxanthohumol levels. Weight, lipids levels, liver enzymes and MCP-1 expression were not affected by beer intake. Non-alcoholic-related beer components protect against hyperlipemia-induced coronary endothelial dysfunction by counteracting vascular oxidative damage and preserving the Akt/eNOS pathway. Light-to-moderate beer consumption prevents and/or reduces the endothelial dysfunction associated with cardiovascular risk factors. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

A single dose of alcohol does not meaningfully alter circadian phase advances and phase delays to light in humans

PubMed Central

Rizvydeen, Muneer; Fogg, Louis F.; Keshavarzian, Ali

2016-01-01

Central circadian timing influences mental and physical health. Research in nocturnal rodents has demonstrated that when alcohol is consumed, it reaches the central hypothalamic circadian pacemaker (suprachiasmatic nuclei) and can directly alter circadian phase shifts to light. In two separate studies, we examined, for the first time, the effects of a single dose of alcohol on circadian phase advances and phase delays to light in humans. Two 23-day within-subjects placebo-controlled counterbalanced design studies were conducted. Both studies consisted of 6 days of fixed baseline sleep to stabilize circadian timing, a 2-day laboratory session, a 6-day break, and a repeat of 6 days of fixed sleep and a 2-day laboratory session. In the phase advance study (n = 10 light drinkers, 24–45 yr), the laboratory sessions consisted of a baseline dim light phase assessment, sleep episode, alcohol (0.6 g/kg) or placebo, 2-h morning bright light pulse, and final phase assessment. In the phase-delay study (n = 14 light drinkers, 22–44 yr), the laboratory sessions consisted of a baseline phase assessment, alcohol (0.8 g/kg) or placebo, 2-h late night bright light pulse, sleep episode, and final phase assessment. In both studies, alcohol either increased or decreased the observed phase shifts to light (interaction P ≥ 0.46), but the effect of alcohol vs. placebo on phase shifts to light was always on average smaller than 30 min. Thus, no meaningful effects of a single dose of alcohol vs. placebo on circadian phase shifts to light in humans were observed. PMID:26936778

A single dose of alcohol does not meaningfully alter circadian phase advances and phase delays to light in humans.

PubMed

Burgess, Helen J; Rizvydeen, Muneer; Fogg, Louis F; Keshavarzian, Ali

2016-04-15

Central circadian timing influences mental and physical health. Research in nocturnal rodents has demonstrated that when alcohol is consumed, it reaches the central hypothalamic circadian pacemaker (suprachiasmatic nuclei) and can directly alter circadian phase shifts to light. In two separate studies, we examined, for the first time, the effects of a single dose of alcohol on circadian phase advances and phase delays to light in humans. Two 23-day within-subjects placebo-controlled counterbalanced design studies were conducted. Both studies consisted of 6 days of fixed baseline sleep to stabilize circadian timing, a 2-day laboratory session, a 6-day break, and a repeat of 6 days of fixed sleep and a 2-day laboratory session. In the phase advance study (n= 10 light drinkers, 24-45 yr), the laboratory sessions consisted of a baseline dim light phase assessment, sleep episode, alcohol (0.6 g/kg) or placebo, 2-h morning bright light pulse, and final phase assessment. In the phase-delay study (n= 14 light drinkers, 22-44 yr), the laboratory sessions consisted of a baseline phase assessment, alcohol (0.8 g/kg) or placebo, 2-h late night bright light pulse, sleep episode, and final phase assessment. In both studies, alcohol either increased or decreased the observed phase shifts to light (interaction P≥ 0.46), but the effect of alcohol vs. placebo on phase shifts to light was always on average smaller than 30 min. Thus, no meaningful effects of a single dose of alcohol vs. placebo on circadian phase shifts to light in humans were observed. Copyright © 2016 the American Physiological Society.

An overview of alcohol and tobacco/nicotine interactions in the human laboratory.

PubMed

Verplaetse, Terril L; McKee, Sherry A

2017-03-01

Alcohol use disorders and tobacco use contribute significant risk to the global burden of disease, and each are major public health concerns. Together, alcohol and tobacco use are highly comorbid and have multiplicative health risks when used concurrently, underscoring the importance of examining alcohol-tobacco interactions in the human laboratory. The aims of this review were to summarize the state of research examining alcohol-tobacco interactions in the human laboratory. We reviewed human laboratory evidence for alcohol and tobacco/nicotine interactions, including 1) craving in drinkers and smokers exposed to smoking or drinking cues, 2) fixed-dosing of alcohol or nicotine in smokers and drinkers, and 3) smoking and alcohol influences on self-administration behaviors. The interactive effects of tobacco/nicotine with other drugs of abuse are also briefly discussed. Overall, results identified that alcohol and tobacco have reciprocal influences on potentiating craving, subjective responses to fixed-dose alcohol or nicotine administration, and self-administration. The literature identified that alcohol increases craving to smoke, decreases time to initiate smoking, and increases smoking self-administration. Similarly, tobacco and nicotine increase alcohol craving, decrease subjective effects of alcohol, and increase alcohol consumption. Future studies should continue to focus on alcohol and tobacco/nicotine interactions in individuals with a wide scope of drinking and smoking histories, different states of alcohol and nicotine deprivation, and influences of either drug on craving, subjective responses, and consumption over the course of the blood alcohol curve. This work could have important implications for the impact of alcohol-tobacco interactions on guiding clinical practice, as well as in the changing landscape of addiction.

Synergistic Interaction of Light Alcohol Administration in the Presence of Mild Iron Overload in a Mouse Model of Liver Injury: Involvement of Triosephosphate Isomerase Nitration and Inactivation

PubMed Central

Gao, Wanxia; Zhao, Jie; Gao, Zhonghong

2017-01-01

It is well known that iron overload promotes alcoholic liver injury, but the doses of iron or alcohol used in studies are usually able to induce liver injury independently. Little attention has been paid to the coexistence of low alcohol consumption and mild iron overload when either of them is insufficient to cause obvious liver damage, although this situation is very common among some people. We studied the interactive effects and the underlining mechanism of mild doses of iron and alcohol on liver injury in a mouse model. Forty eight male Kunming mice were randomly divided into four groups: control, iron (300 mg/kg iron dextran, i.p.), alcohol (2 g/kg/day ethanol for four weeks i.g.), and iron plus alcohol group. After 4 weeks of treatment, mice were sacrificed and blood and livers were collected for biochemical analysis. Protein nitration level in liver tissue was determined by immunoprecipitation and Western blot analysis. Although neither iron overload nor alcohol consumption at our tested doses can cause severe liver injury, it was found that co-administration of the same doses of alcohol and iron resulted in liver injury and hepatic dysfunction, accompanied with elevated ratio of NADH/NAD+, reduced antioxidant ability, increased oxidative stress, and subsequent elevated protein nitration level. Further study revealed that triosephosphate isomerase, an important glycolytic enzyme, was one of the targets to be oxidized and nitrated, which was responsible for its inactivation. These data indicate that even under low alcohol intake, a certain amount of iron overload can cause significant liver oxidative damage, and the modification of triosephosphate isomerasemight be the important underlining mechanism of hepatic dysfunction. PMID:28103293

Evaluation of an Alcohol Withdrawal Protocol and a Preprinted Order Set at a Tertiary Care Hospital

PubMed Central

Ng, Karen; Dahri, Karen; Chow, Ivy; Legal, Michael

2011-01-01

Background: Alcohol withdrawal protocols involving symptom-triggered administration of benzodiazepine have been established to reduce the duration of treatment and the cumulative benzodiazepine dose (relative to usual care). However, the effects of a protocol combining fixed-schedule and symptom-triggered benzodiazepine dosing are less clear. Objective: To assess the efficacy and safety of a combination fixed-scheduled and symptom-triggered benzodiazepine dosing protocol for alcohol withdrawal, relative to usual care, for medical inpatients at a tertiary care hospital. Methods: A chart review of admissions to the internal medicine service for alcohol withdrawal was conducted to compare treatment outcomes before (October 2005 to April 2007) and after (October 2007 to April 2009) implementation of the combination protocol. The primary outcome was duration of benzodiazepine treatment for alcohol withdrawal. The secondary outcomes were cumulative benzodiazepine dose administered, safety implications, and use of adjunctive medications. Results: A total of 159 patients met the inclusion criteria. Assessable data were available for 71 charts from the pre-implementation period and 72 charts from the post-implementation period. The median duration of benzodiazepine treatment was 91 h before implementation and 57 h after implementation (p < 0.001). Use of the protocol was also associated with a significant reduction in severe complications of alcohol withdrawal (50% versus 33%, p = 0.019), median cumulative benzodiazepine dose (in lorazepam equivalents) (20.0 mg versus 15.5 mg, p = 0.026), and use of adjunctive medications (65% versus 38%, p = 0.001). The incidence of serious adverse outcomes of treatment with benzodiazepines was not significantly different between the 2 groups. Conclusions: Implementation of an alcohol withdrawal protocol with a combination of fixed-schedule and symptom-triggered benzodiazepine dosing in a medical ward was associated with a shorter duration of benzodiazepine use and a lower incidence of severe complications of alcohol withdrawal. PMID:22479099

Effect on White Grape Must of Multiflora Bee Pollen Addition during the Alcoholic Fermentation Process.

PubMed

Amores-Arrocha, Antonio; Roldán, Ana; Jiménez-Cantizano, Ana; Caro, Ildefonso; Palacios, Víctor

2018-05-31

The aim of the present study was to compare and analyze the impact of using bee pollen doses (0.1, 0.25, 1, 5, 10 and 20 g/L) as activator in the alcoholic fermentation process of Palomino fino and Riesling wines. In this regard, its influence on the musts composition, the fermentative kinetics, the evolution of the populations of Saccharomyces cerevisiae , the evolution of yeast-assimilable nitrogen and physico-chemical characteristics of final wines has been analyzed. Bee pollen addition produces significant increases in yeast-assimilable nitrogen and maximum yeasts population and exponential velocity reached during alcoholic fermentation. Bee pollen showed an important effect on yeast survival during the death phase. Final wines showed significantly increase in volatile acidity above doses higher than 10 g/L and Comisión Internacional de L'Eclairage parameters (CIELab), color intensity and Abs 420 nm, from 1 g/L. Therefore, pollen could be used as fermentative activator for the alcoholic fermentation of white wines applying doses below of 1 g/L.

Effects of naltrexone on alcohol drinking patterns and extinction of alcohol seeking in baboons

PubMed Central

Kaminski, Barbara J.; Duke, Angela N.; Weerts, Elise M.

2012-01-01

Rationale Understanding naltrexone’s effect on motivation to drink and pattern of drinking is important for better treatment outcomes and for comparison with novel medications. Objectives Naltrexone’s effects on number and pattern of seeking, self-administration, and extinction responses were evaluated in two groups of baboons trained under a 3 component chained schedule of reinforcement (CSR). Methods Alcohol (4% w/v; n=4; Alcohol Group) or a preferred non-alcoholic beverage (n=4; Control Group) was available for self-administration only in Component 3 of the CSR. Responses in Component 2 provided indices of motivation to drink (seeking). Naltrexone (0.32 – 3.2 mg/kg) and saline were administered before drinking and Component 2 extinction sessions. Results Acute doses of naltrexone significantly decreased total self-administration responses (p<0.01), intake volume (p<0.001) and g/kg of alcohol (p<0.01) in the Alcohol Group only. Pattern of drinking did not change, but number of drinks during the initial drinking bout was decreased significantly by naltrexone for both groups (P<0.05). During within-session extinction tests, acute naltrexone significantly decreased time to reach extinction (p<0.01) and number of seeking responses (p<0.05), particularly early in the extinction period in the Alcohol Group only. When administered chronically, naltrexone did not decrease progressive-ratio breaking points to gain access to alcohol, but dose-dependently reduced alcohol self-administration (p<0.05) by decreasing the magnitude of the initial drinking bout. Conclusions The results support clinical observations that naltrexone may be most effective at reducing self-administration in the context of ongoing alcohol availability and may reduce motivation to drink in the presence of alcohol-related cues. PMID:22451093

Protective influences of N-acetylcysteine against alcohol abstinence-induced depression by regulating biochemical and GRIN2A, GRIN2B gene expression of NMDA receptor signaling pathway in rats.

PubMed

Yawalkar, Rutuja; Changotra, Harish; Gupta, Girdhari Lal

2018-04-25

Evidences have indicated a high degree of comorbidity of alcoholism and depression. N-acetylcysteine (NAC) has shown its clinical efficiency in the treatment of several psychiatric disorders and is identified as a multi-target acting drug. The ability of NAC to prevent alcohol abstinence-induced depression-like effects and underlying mechanism(s) have not been adequately addressed. This study was aimed to investigate the beneficial effects of NAC in the alcohol abstinence-induced depression developed following long-term voluntary alcohol intake. For evaluation of the effects of NAC, Sprague-Dawley rats were enabled to voluntary drinking of 4.5%, 7.5% and 9% v/v alcohol for fifteen days. NAC (25, 50, and 100 mg/kg) and fluoxetine (5 mg/kg) were injected intraperitoneally for three consecutive days during the alcohol abstinence period on the days 16, 17, 18. The behavioral studies were conducted employing forced swim test (FST), and tail suspension test (TST) on day 18 to determine the effects of N-acetylcysteine and fluoxetine in the ethanol withdrawal induced-depression. Blood alcohol concentration, alcohol biomarkers like SGPT, SGOT, ALP, GGT, and MCV were estimated by using commercially available kits. Serotonin concentrations were measured in the plasma, hippocampus and pre-frontal cortex using the rat ELISA kit. The expression of GRIN1, GRIN2A, GRIN2B genes for the N-methyl d-aspartate receptors (NMDAR) subunits in the hippocampus and the prefrontal cortex were also examined by reverse-transcription quantitative polymerase chain reaction. The results revealed that alcohol abstinence group depicted increased immobility time in FST and TST. Further, NAC exerted significant protective effect at the doses 50 mg/kg and 100 mg/kg, but 25 mg/kg showed insignificant protection against alcohol abstinence-induced depression. The increased level of biochemical parameters following ethanol abstinence were also reversed by NAC at the dose of 100 mg/kg. The significant reversal effect of NAC on the serotonin level following alcohol abstinence was greater in the hippocampus as compared to the third-day alcohol withdrawal group. The increased expression levels of GRIN2A and GRIN2B following ethanol abstinence were reversed with a higher dose of NAC (100 mg/kg) treatment. In conclusion, the results of the study reveal that NAC has remarkable protective effects in the alcohol abstinence-induced depression by modulating alcohol markers, serotonin levels and GRIN2A, GRIN2B gene expression of NMDAR signaling pathway in rats. Copyright © 2018 Elsevier Ltd. All rights reserved.

An overview of alcohol and tobacco/nicotine interactions in the human laboratory

PubMed Central

Verplaetse, Terril L.; McKee, Sherry A.

2017-01-01

Alcohol use disorders and tobacco use contribute significant risk to the global burden of disease, and each are major public health concerns. Together, alcohol and tobacco use are highly comorbid and have multiplicative health risks when used concurrently, underscoring the importance of examining alcohol-tobacco interactions in the human laboratory. The aims of this review were to summarize the state of research examining alcohol-tobacco interactions in the human laboratory, including 1) craving in drinkers and smokers exposed to smoking or drinking cues, 2) fixed-dosing of alcohol or nicotine in smokers and drinkers, and 3) smoking and alcohol influences on self-administration behaviors. The interactive effects of tobacco/nicotine with other drugs of abuse are also briefly discussed. Overall, results identified that alcohol and tobacco have reciprocal influences on potentiating craving, subjective responses to fixed-dose alcohol or nicotine administration, and self-administration. The literature identified that alcohol increases craving to smoke, decreases time to initiate smoking, and increases smoking self-administration. Similarly, tobacco and nicotine increase alcohol craving, decrease subjective effects of alcohol, and increase alcohol consumption. Future studies should continue to focus on alcohol and tobacco/nicotine interactions in individuals with a wide scope of drinking and smoking histories, different states of alcohol and nicotine deprivation, and influences of either drug on craving, subjective responses, and consumption over the course of the blood alcohol curve. This work could have important implications for the impact of alcohol-tobacco interactions on guiding clinical practice, as well as in the changing landscape of addiction. PMID:27439453

Effects of methylmercury and alcohol exposure in Drosophila melanogaster: Potential risks in neurodevelopmental disorders.

PubMed

Chauhan, Ved; Chauhan, Abha

2016-06-01

Extensive evidence suggests the role of oxidative stress in autism and other neurodevelopmental disorders. In this study, we investigated whether methylmercury (MeHg) and/or alcohol exposure has deleterious effects in Drosophila melanogaster (fruit flies). A diet containing different concentrations of MeHg in Drosophila induced free radical generation and increased lipid peroxidation (markers of oxidative stress) in a dose-dependent manner. This effect of MeHg on oxidative stress was enhanced by further exposure to alcohol. It was observed that alcohol alone could also induce free radical generation in flies. After alcohol exposure, MeHg did not affect the immobilization of flies, but it increased the recovery time in a concentration-dependent manner. MeHg significantly inhibited the activity of alcohol dehydrogenase (ADH) in a dose-dependent manner. Linear regression analysis showed a significant negative correlation between ADH activity and recovery time upon alcohol exposure in the flies fed a diet with MeHg. This relationship between ADH activity and recovery time after alcohol exposure was confirmed by adding 4-methyl pyrazole (an inhibitor of ADH) to the diet for the flies. These results suggest that consumption of alcohol by pregnant mothers who are exposed to MeHg may lead to increased oxidative stress and to increased length of time for alcohol clearance, which may have a direct impact on the development of the fetus, thereby increasing the risk of neurodevelopmental disorders. Published by Elsevier Ltd.

Taxes on tobacco, alcohol and sugar sweetened beverages: Linkages and lessons learned.

PubMed

Blecher, Evan

2015-07-01

Increased consumption of sugar-sweetened beverages (SSBs) has been linked to increases in obesity in both high-income and low- and middle-income countries. Tobacco and alcohol taxes have proven to be effective tools to reduce tobacco and alcohol use. Many public health advocates propose using similar taxes to reduce consumption of SSBs. South Africa is a middle-income country that is considered a leader in the area of tobacco tax policy. A case study of tobacco and alcohol taxes is used to better understand optimal tax structures for SSBs. The case study tracks aggregate data over time on taxes, prices, consumption, tax revenues, and marketing expenditures at the brand level. Tobacco and alcohol taxes are shown to be effective in reducing the demand for tobacco. Additionally, taxes on the dose of alcohol rather than the volume of the beverage may incentivize producers to reduce the volume of alcohol in beverages through the supply side. While specific taxes based on the volume of beverages are likely to reduce the demand for SSBs, policy makers should also consider taxes on alcohol and SSBs that tax the dose of the alcohol and calories in order to create supply-side incentives for producers to lower alcohol and calorie levels in existing products or promote products with lower levels of alcohol and calories. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dose-dependent suppression by ethanol of transient auditory 40-Hz response.

PubMed

Jääskeläinen, I P; Hirvonen, J; Saher, M; Pekkonen, E; Sillanaukee, P; Näätänen, R; Tiitinen, H

2000-02-01

Acute alcohol (ethanol) challenge is known to induce various cognitive disturbances, yet the neural basis of the effect is poorly known. The auditory transient evoked gamma-band (40-Hz) oscillatory responses have been suggested to be associated with various perceptual and cognitive functions in humans; however, alcohol effects on auditory 40-Hz responses have not been investigated to date. The objective of the study was to test the dose-related impact of alcohol on auditory transient evoked 40-Hz responses during a selective-attention task. Ten healthy social drinkers ingested, in four separate sessions, 0.00, 0. 25, 0.50, or 0.75 g/kg of 10% (v/v) alcohol solution. The order of the sessions was randomized and a double-blind procedure was employed. During a selective attention task, 300-Hz standard and 330-Hz deviant tones were presented to the left ear, and 1000-Hz standards and 1100-Hz deviants to the right ear of the subjects (P=0. 425 for each standard, P=0.075 for each deviant). The subjects attended to a designated ear, and were to detect the deviants therein while ignoring tones to the other ear. The auditory transient evoked 40-Hz responses elicited by both the attended and unattended standard tones were significantly suppressed by the 0.50 and 0.75 g/kg alcohol doses. Alcohol suppresses auditory transient evoked 40-Hz oscillations already with moderate blood alcohol concentrations. Given the putative role of gamma-band oscillations in cognition, this finding could be associated with certain alcohol-induced cognitive deficits.

Comparison of Alcohol Impairment of Behavioral and Attentional Inhibition

PubMed Central

Weafer, Jessica; Fillmore, Mark T.

2012-01-01

Background Despite the wealth of studies demonstrating the impairing effects of alcohol on behavioral inhibition, less is known regarding effects of the drug on attentional inhibition (i.e., the ability to ignore distracting stimuli in the environment in order to focus attention on relevant information). The current study examined alcohol impairment of both behavioral and attentional inhibition, as well as potential associations between the two mechanisms of inhibitory control. Methods Men (n = 27) and women (n = 21) performed a measure of behavioral inhibition (cued go/no-go task) and a measure of attentional inhibition (delayed ocular return task) following three doses of alcohol: 0.65 g/kg, 0.45 g/kg, and 0.0 g/kg (placebo). Results Alcohol impaired both behavioral and attentional inhibition relative to placebo; however, correlational analyses revealed no associations between measures of behavioral and attentional inhibition following any dose. Additionally, men committed more inhibitory failures on the behavioral inhibition task, whereas women committed more inhibitory failures on the attentional inhibition task. Conclusions These findings suggest that behavioral and attentional inhibition are equally sensitive to the impairing effects of alcohol, yet represent distinct components of inhibitory control. Additionally, the observed gender differences in control of behavior and attention could have important implications regarding negative consequences associated with alcohol-induced disinhibition in men and women. PMID:22673197

Alcohol Effects on Simulated Driving in Frequent and Infrequent Binge Drinkers

PubMed Central

Bernosky-Smith, Kimberly A.; Shannon, Erin E.; Roth, Alicia J.; Liguori, Anthony

2011-01-01

Objective Compared to non-bingers, binge drinkers are more likely to drive while intoxicated. The extent to which binge frequency impacts confidence in driving and subsequent driving impairment is unknown. This study compared the effects of an experimenter-delivered alcohol binge on subjective impairment and simulated driving ability in female High and Low Frequency bingers. Methods Female drinkers were assigned to High Frequency (n=30) or Low Frequency (n=30) binge groups based on their Alcohol Use Questionnaire responses. At 30-minute intervals within a two-hour period, participants received either a placebo drink (n=15 per group) or a 0.2 g/kg dose of alcohol (n=15 per group; cumulative dose 0.8 g/kg). Self-reported impairment, driving confidence, and simulated driving were then measured. Results Self-reported confidence in driving was significantly lower after alcohol than after placebo in Low Frequency but not High Frequency bingers. Self-reported impairment and collisions during simulated driving were significantly greater after alcohol than after placebo in both Low Frequency and High Frequency bingers. Conclusions The impairing effects of a single alcohol binge on driving ability in females are not influenced by binge frequency. However, high binge frequency may be associated with a less cautious approach to post-binge driving. PMID:21542027

Amphetamine self-administration in light and moderate drinkers.

PubMed

Stanley, Matthew D; Poole, Mégan M; Stoops, William W; Rush, Craig R

2011-03-01

Light and moderate drinkers respond differently to the effects of abused drugs, including stimulants such as amphetamine. The purpose of this study was to determine whether light and moderate drinkers differ in their sensitivity to the reinforcing and subjective effects of d-amphetamine. We hypothesized that moderate drinkers (i.e., participants that reported consuming at least seven alcohol-containing beverages per week) would be more sensitive to the reinforcing and positive subject-rated effects of d-amphetamine than light drinkers. Data from four studies that employed similar d-amphetamine self-administration procedures and subject-rated drug-effect measures were included in the analysis. Light (n = 17) and moderate (n = 16) drinkers sampled placebo, low (8 to 10 mg), and high (16 to 20 mg) doses of oral d-amphetamine administered in eight capsules. Following sampling sessions, participants worked for a maximum of eight capsules, each containing 12.5% of the previously sampled dose, on a modified progressive-ratio schedule of reinforcement. Both active doses of d-amphetamine functioned as a reinforcer in the moderate drinkers, while only the high dose did so in the light drinkers. The moderate drinkers worked for significantly more capsules that contained the high dose of d-amphetamine than did the light drinkers. d-Amphetamine produced prototypical stimulant-like subjective effects (e.g., dose-dependent increases in ratings of Good Effects; Like Drug and Willing to Take Again). Moderate drinkers reported significantly greater subjective effects than the light drinkers. These results are consistent with those from previous laboratory experiments and suggest that moderate alcohol consumption may increase vulnerability to the abuse-related effects of stimulants. Copyright © 2010 by the Research Society on Alcoholism.

Childhood Sexual Abuse and Acute Alcohol Effects on Men’s Sexual Aggression Intentions

PubMed Central

Davis, Kelly Cue; Schraufnagel, Trevor J.; Jacques-Tiura, Angela J.; Norris, Jeanette; George, William H.; Kiekel, Preston A.

2012-01-01

Objective Although research has established childhood sexual abuse (CSA) as a risk factor for men’s perpetration of sexual aggression, there has been little investigation of the factors undergirding this association. This study represents one of the first to use a laboratory-based sexual aggression analogue coupled with an alcohol administration protocol to investigate the pathways through which CSA and alcohol influence men’s self-reported sexual aggression intentions. Method After completing background questionnaires, male social drinkers (N = 220) were randomly assigned to a control, placebo, low alcohol dose or high alcohol dose condition. Following beverage consumption, participants read a sexual scenario in which the female partner refused to have unprotected sexual intercourse, after which they completed dependent measures. Results Path analysis indicated that men with a CSA history and intoxicated men perceived the female character as more sexually aroused and reported stronger sexual entitlement cognitions, both of which were in turn associated with greater condom use resistance and higher sexual aggression intentions. Exploratory analyses revealed that intoxication moderated the effects of CSA history on sexual entitlement cognitions, such that sexual entitlement cognitions were highest for men who had a CSA history and consumed alcohol. Conclusions Findings suggest that CSA history may facilitate sexual assault perpetration through its effects on in-the-moment cognitions, and that these effects may be exacerbated by alcohol intoxication. PMID:22754720

[Prophylaxis of alcoholic disease of the liver].

PubMed

Beliakin, S A

2009-08-01

Military doctors should have a uniform position to the use of alcohol. Now alcohol is the basic pathogenic factor in development of a lethal cirrhosis of a liver. The most known sayings justifying the use of alcohol, are insolvent. Useful doses of alcohol does not exist. The quantity of used alcohol has the great value. Only at achievement of age 21 year it is possible to use safe doses of alcohol. A safe dose of pure alcohol (ethanol) less than 30,0 in day. In a basis of prophylaxis of a cirrhosis of a liver there is a medical educational activity.

The effects of moderate alcohol concentrations on driving and cognitive performance during ascending and descending blood alcohol concentrations.

PubMed

Starkey, Nicola J; Charlton, Samuel G

2014-07-01

Alcohol has an adverse effect on driving performance; however, the effects of moderate doses on different aspects of the driving task are inconsistent and differ across the intoxication curve. This research aimed to investigate driving and cognitive performance asymmetries (acute tolerance and acute protracted error) accompanying the onset and recovery from moderate alcohol consumption. Sixty-one participants received a placebo, medium (target blood alcohol concentration [BAC] 0.05 mg/ml) or high (target BAC 0.08 mg/ml) dose of alcohol. Participants completed a simulated drive, cognitive tests and subjective rating scales five times over a 3.5 h period. When ascending and descending BACs (0.05 and 0.09 mg/ml) were compared participants' self-ratings of intoxication and willingness to drive showed acute tolerance. Acute protracted errors were observed for response speed, maze learning errors, time exceeding the speed limit and exaggerated steering responses to hazards. Participants' estimates of their level of intoxication were poorly related to their actual BAC levels (and hence degree of impairment), and various aspects of driving and cognitive performance worsened during descending BACs. This indicates that drivers are not good at judging their fitness to drive after drinking only moderate amounts of alcohol and suggests an important focus for public education regarding alcohol and driving. Copyright © 2014 John Wiley & Sons, Ltd.

Does beer, wine or liquor consumption correlate with the risk of renal cell carcinoma? A dose-response meta-analysis of prospective cohort studies

PubMed Central

Xu, Xin; Zhu, Yi; Zheng, Xiangyi; Xie, Liping

2015-01-01

Despite plenty of evidence supports an inverse association between alcohol drinking and risk of renal cell carcinoma (RCC), sex-specific and beverage-specific dose-response relationships have not been well established. We examined this association by performing a systematic review and meta-analysis of prospective studies. Studies were identified by comprehensively searching PubMed and EMBASE databases through February 21, 2015. Categorical and dose-response meta-analyses were conducted to identify the effects of alcohol on RCC. A total of eight publications (including seven cohort studies and one pooled analysis of 12 cohort studies) were eligible for this meta-analysis. Dose-response analysis showed that each 5 g/day increment of alcohol intake corresponded to a 5% decrease in risk of RCC for males and 9% for females. Alcohol intakes from wine, beer, and liquor were each associated with a reduced risk of RCC. When these associations were examined separately by gender, statistically significant inverse associations were restricted to alcohol from wine among females (RR = 0.82, 95% CI 0.73–0.91) and to alcohol from beer and from liquor among males (RR = 0.87, 95% CI 0.83–0.91 and RR = 0.95, 95% CI 0.92–0.99, respectively). In conclusion, there exist gender-specific and beverage-specific differences in the association between alcohol intake and RCC risk. PMID:25965820

Baclofen and naltrexone effects on alcohol self-administration: Comparison of treatment initiated during abstinence or ongoing alcohol access in baboons.

PubMed

Holtyn, August F; Kaminski, Barbara J; Weerts, Elise M

2017-10-01

Baclofen, a GABA B receptor agonist, is under investigation as a pharmacotherapy for alcohol use disorder. Treatment with a pharmacotherapeutic can be initiated during alcohol abstinence or active drinking, which may influence treatment outcomes. This study examined whether baclofen treatment initiated and maintained during alcohol abstinence would reduce alcohol seeking and self-administration upon return to alcohol access, and whether effects differed from treatment initiated and maintained during ongoing alcohol access. Naltrexone was tested under similar conditions for comparison. Five baboons self-administered alcohol under a three-component chained schedule of reinforcement that modeled periods of anticipation (Component 1), seeking (Component 2), and consumption (Component 3). Alcohol was only available in Component 3. In Experiment 1, baclofen (0.1-1.8mg/kg) or naltrexone (1.0-5.6mg/kg) was administered daily beginning on the first day of a 5-day abstinence period and treatment was continued for 5days of alcohol access. In Experiment 2, selected doses of both drugs were administered during ongoing alcohol access. When treatment was initiated during alcohol abstinence, baclofen and naltrexone did not significantly reduce total alcohol intake (g/kg) or alcohol seeking. In comparison, when treatment was initiated during ongoing alcohol access, both baclofen (1.8mg/kg) and naltrexone (3.2 and 5.6mg/kg) significantly reduced total alcohol intake (g/kg). Naltrexone (5.6mg/kg), but not baclofen, significantly reduced alcohol seeking. Initiation of baclofen treatment (or other alcohol use disorder treatments) during abstinence or active drinking may be an important factor in influencing efficacy and appropriate dose selection. Copyright © 2017 Elsevier B.V. All rights reserved.

[The effects of small amounts of alcohol on in-flight activity].

PubMed

Dionisi, A

1981-10-06

Alcohol metabolism is described prior to an account of its effect on vigilance. The psychological and psychosomatic influence of alcohol is also illustrated in the light of experimental data indicating how it alters the response to stimuli. Alterations in various parameters following the administration of significantly small doses of alcohol were studied. Reaction time decreased, then increased, followed by a further decrease after about 1 1/2 hr. Even 1/8th litre depresses receptiveness of the reticular substance, and leads to lengthening of reaction times due to diminished ability to concentrate attention on a given task. CNS depression is also in proportion to the complexity of the performance required. This is particularly and dangerous in pilots, whose tasks are extremely precise and require close attention. Functional alterations induced by alcohol during flight may be numerous, due to disturbances connected with the specific conditions created by flying, and apparatuses whose physiological functions are susceptible to disturbance by flying itself. Alcohol, itself a harmful influence on piloting an aircraft, deteriorates these functions and conditions. Toxic substances present during flying and their potentiation by alcohol are considered. The effects of alcohol, added to these specific pathogenetic toxic effects, quickly and readily lead to a fall in overall psychophysical efficiency, and prejudice flight safety. the reason why a decrease in the limit intake doses to less than 2 cc/kg, equivalent to a blood value of 0.5 g 0/00, to ensure safe control of the plane, is desirable is explained.

Moderate sleep deprivation produces impairments in cognitive and motor performance equivalent to legally prescribed levels of alcohol intoxication

PubMed Central

Williamson, A; Feyer, A.

2000-01-01

OBJECTIVES—To compare the relative effects on performance of sleep deprivation and alcohol.
METHODS—Performance effects were studied in the same subjects over a period of 28 hours of sleep deprivation and after measured doses of alcohol up to about 0.1% blood alcohol concentration (BAC). There were 39 subjects, 30 employees from the transport industry and nine from the army.
RESULTS—After 17-19 hours without sleep, corresponding to 2230 and 0100, performance on some tests was equivalent or worse than that at a BAC of 0.05%. Response speeds were up to 50% slower for some tests and accuracy measures were significantly poorer than at this level of alcohol. After longer periods without sleep, performance reached levels equivalent to the maximum alcohol dose given to subjects (BAC of 0.1%).
CONCLUSIONS—These findings reinforce the evidence that the fatigue of sleep deprivation is an important factor likely to compromise performance of speed and accuracy of the kind needed for safety on the road and in other industrial settings.


Keywords: sleep deprivation; performance; alcohol PMID:10984335

Antidepressant sales and the risk for alcohol-related and non-alcohol-related suicide in Finland--an individual-level population study.

PubMed

Moustgaard, Heta; Joutsenniemi, Kaisla; Myrskylä, Mikko; Martikainen, Pekka

2014-01-01

A marked decline in suicide rates has co-occurred with increased antidepressant sales in several countries but the causal connection between the trends remains debated. Most previous studies have focused on overall suicide rates and neglected differential effects in population subgroups. Our objective was to investigate whether increasing sales of non-tricyclic antidepressants have reduced alcohol- and non-alcohol-related suicide risk in different population subgroups. We followed a nationally representative sample of 950,158 Finnish adults in 1995-2007 for alcohol-related (n = 2,859) and non-alcohol-related (n = 8,632) suicides. We assessed suicide risk by gender and social group according to regional sales of non-tricyclic antidepressants, measured by sold doses per capita, prevalence of antidepressant users, and proportion of antidepressant users with doses reflecting minimally adequate treatment. Fixed-effects Poisson regression models controlled for regional differences and time trends that may influence suicide risk irrespective of antidepressant sales. The number of sold antidepressant doses per capita and the prevalence of antidepressant users were unrelated to male suicide risk. However, one percentage point increase in the proportion of antidepressant users receiving minimally adequate treatment reduced non-alcohol-related male suicide risk by one percent (relative risk 0.987, 95% confidence interval 0.976-0.998). This beneficial effect only emerged among men with high education, high income, and employment, among men without a partner, and men not owning their home. Alcohol-related suicides and female suicides were unrelated to all measures of antidepressant sales. We found little evidence that increase in overall sales or in the prevalence of non-tricyclic antidepressant users would have caused the fall in suicide rates in Finland in 1995-2007. However, the rise in the proportion of antidepressant users receiving minimally adequate treatment, possibly due to enhanced treatment compliance, may have prevented non-alcohol-related suicides among men.

Antidepressant Sales and the Risk for Alcohol-Related and Non-Alcohol-Related Suicide in Finland—An Individual-Level Population Study

PubMed Central

Moustgaard, Heta; Joutsenniemi, Kaisla; Myrskylä, Mikko; Martikainen, Pekka

2014-01-01

Objectives A marked decline in suicide rates has co-occurred with increased antidepressant sales in several countries but the causal connection between the trends remains debated. Most previous studies have focused on overall suicide rates and neglected differential effects in population subgroups. Our objective was to investigate whether increasing sales of non-tricyclic antidepressants have reduced alcohol- and non-alcohol-related suicide risk in different population subgroups. Methods We followed a nationally representative sample of 950,158 Finnish adults in 1995–2007 for alcohol-related (n = 2,859) and non-alcohol-related (n = 8,632) suicides. We assessed suicide risk by gender and social group according to regional sales of non-tricyclic antidepressants, measured by sold doses per capita, prevalence of antidepressant users, and proportion of antidepressant users with doses reflecting minimally adequate treatment. Fixed-effects Poisson regression models controlled for regional differences and time trends that may influence suicide risk irrespective of antidepressant sales. Results The number of sold antidepressant doses per capita and the prevalence of antidepressant users were unrelated to male suicide risk. However, one percentage point increase in the proportion of antidepressant users receiving minimally adequate treatment reduced non-alcohol-related male suicide risk by one percent (relative risk 0.987, 95% confidence interval 0.976–0.998). This beneficial effect only emerged among men with high education, high income, and employment, among men without a partner, and men not owning their home. Alcohol-related suicides and female suicides were unrelated to all measures of antidepressant sales. Conclusion We found little evidence that increase in overall sales or in the prevalence of non-tricyclic antidepressant users would have caused the fall in suicide rates in Finland in 1995–2007. However, the rise in the proportion of antidepressant users receiving minimally adequate treatment, possibly due to enhanced treatment compliance, may have prevented non-alcohol-related suicides among men. PMID:24892560

Chronic alcohol abuse and the acute sedative and neurophysiologic effects of midazolam.

PubMed

Bauer, L O; Gross, J B; Meyer, R E; Greenblatt, D J

1997-10-01

The aim of the present investigation was to examine benzodiazepine sensitivity in abstinent alcoholics. For this purpose, two escalating doses of the benzodiazepine midazolam were i.v. administered to nine alcohol-dependent patients after 2-3 weeks of abstinence and 12 healthy, non-alcoholic volunteers. A variety of dependent measures were examined, including the power spectrum of the resting electroencephalogram (EEG) and evoked EEG responses, saccadic eye movements, self-reported sedation, and vigilance task performance. Analyses revealed a significant association between plasma midazolam levels and changes in EEG beta power, pattern shift visual evoked potential amplitude, heart rate, and saccade amplitude and velocity. The patient and control groups differed significantly in the onset latencies of their saccadic eye movements, and marginally in EEG beta power, both before and after midazolam. However, no differences were detected between the groups in the dose of midazolam required to produce sedation or in midazolam's neurophysiological effects.

Continuous delivery of naltrexone and nalmefene leads to tolerance in reducing alcohol drinking and to supersensitivity of brain opioid receptors.

PubMed

Korpi, Esa R; Linden, Anni-Maija; Hytönen, Heidi R; Paasikoski, Nelli; Vashchinkina, Elena; Dudek, Mateusz; Herr, Deron R; Hyytiä, Petri

2017-07-01

Opioid antagonist treatments reduce alcohol drinking in rodent models and in alcohol-dependent patients, with variable efficacy across different studies. These treatments may suffer from the development of tolerance and opioid receptor supersensitivity, as suggested by preclinical models showing activation of these processes during and after subchronic high-dose administration of the short-acting opioid antagonist naloxone. In the present study, we compared equipotent low and moderate daily doses of naltrexone and nalmefene, two opioid antagonists in the clinical practice for treatment of alcoholism. The antagonists were given here subcutaneously for 7 days either as daily injections or continuous osmotic minipump-driven infusions to alcohol-preferring AA rats having trained to drink 10% alcohol in a limited access protocol. One day after stopping the antagonist treatment, [ 35 S]GTPγS autoradiography on brain cryostat sections was carried out to examine the coupling of receptors to G protein activation. The results prove the efficacy of repeated injections over infused opioid antagonists in reducing alcohol drinking. Tolerance to the reducing effect on alcohol drinking and to the enhancement of G protein coupling to μ-opioid receptors in various brain regions were consistently detected only after infused antagonists. Supersensitivity of κ-opioid receptors was seen in the ventral and dorsal striatal regions especially by infused nalmefene. Nalmefene showed no clear agonistic activity in rat brain sections or at human recombinant κ-opioid receptors. The findings support the as-needed dosing practice, rather than the standard continual dosing, in the treatment of alcoholism with opioid receptor antagonists. © 2016 Society for the Study of Addiction.

Effects of caffeine and Bombesin on ethanol and food intake

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dietze, M.A.; Kulkosky, P.J.

1991-01-01

The methylxanthine caffeine and ethyl alcohol are widely used and powerful psychotropic drugs, but their interactions are not well understood. Bombesin is a brain-gut neuropeptide which is thought to function as a neurochemical factor in the inhibitory control of voluntary alcohol ingestion. We assessed the effects of combinations of intraperitoneal doses of caffeine and bombesin on 5% w/v ethanol solution and food intake in deprived rats. Deprived male and female Wistar rats received access to 5% ethanol or Purina chow for 30 minutes after i.p. injections. In single doses, CAF and BBS significantly decreased both ethanol and food consumption, atmore » 50 mg/kg and 10 {mu}g/kg, respectively. CAF and BBS combinations produced infra-additive, or less-than-expected inhibitory effects on ethanol intake, but simple additive inhibitory effects on food intake. This experimental evidence suggests a reciprocal blocking of effects of CAF and BBS on ethanol intake but not food intake. Caffeine, when interacting and bombesin, increases alcohol consumption beyond expected values. Caffeine could affect the operation of endogenous satisfy signals for alcohol consumption.« less

Characterization of Exercise and Alcohol Self-Management Behaviors of Type 1 Diabetes Patients on Insulin Pump Therapy.

PubMed

Grando, Maria Adela; Groat, Danielle; Soni, Hiral; Boyle, Mary; Bailey, Marilyn; Thompson, Bithika; Cook, Curtiss B

2017-03-01

There is a lack of systematic ways to analyze how diabetes patients use their insulin pumps to self-manage blood glucose to compensate for alcohol ingestion and exercise. The objective was to analyze "real-life" insulin dosing decisions occurring in conjunction with alcohol intake and exercise among patients using insulin pumps. We recruited adult type 1 diabetes (T1D) patients on insulin pump therapy. Participants were asked to maintain their daily routines, including those related to exercising and consuming alcohol, and keep a 30-day journal on exercise performed and alcohol consumed. Thirty days of insulin pump data were downloaded. Participants' actual insulin dosing behaviors were compared against their self-reported behaviors in the setting of exercise and alcohol. Nineteen T1D patients were recruited and over 4000 interactions with the insulin pump were analyzed. The analysis exposed variability in how subjects perceived the effects of exercise/alcohol on their blood glucose, inconsistencies between self-reported and observed behaviors, and higher rates of blood glucose control behaviors for exercise versus alcohol. Compensation techniques and perceptions on how exercise and alcohol affect their blood glucose levels vary between patients. Improved individualized educational techniques that take into consideration a patient's unique life style are needed to help patients effectively apply alcohol and exercise compensation techniques.

Differences of acute versus chronic ethanol exposure on anxiety-like behavioral responses in zebrafish.

PubMed

Mathur, Priya; Guo, Su

2011-06-01

Zebrafish, a vertebrate model organism amenable to high throughput screening, is an attractive system to model and study the mechanisms underlying human diseases. Alcoholism and alcoholic medical disorders are among the most debilitating diseases, yet the mechanisms by which ethanol inflicts the disease states are not well understood. In recent years zebrafish behavior assays have been used to study learning and memory, fear and anxiety, and social behavior. It is important to characterize the effects of ethanol on zebrafish behavioral repertoires in order to successfully harvest the strength of zebrafish for alcohol research. One prominent effect of alcohol in humans is its effect on anxiety, with acute intermediate doses relieving anxiety and withdrawal from chronic exposure increasing anxiety, both of which have significant contributions to alcohol dependence. In this study, we assess the effects of both acute and chronic ethanol exposure on anxiety-like behaviors in zebrafish, using two behavioral paradigms, the Novel Tank Diving Test and the Light/Dark Choice Assay. Acute ethanol exposure exerted significant dose-dependent anxiolytic effects. However, withdrawal from repeated intermittent ethanol exposure disabled recovery from heightened anxiety. These results demonstrate that zebrafish exhibit different anxiety-like behavioral responses to acute and chronic ethanol exposure, which are remarkably similar to these effects of alcohol in humans. Because of the accessibility of zebrafish to high throughput screening, our results suggest that genes and small molecules identified in zebrafish will be of relevance to understand how acute versus chronic alcohol exposure have opposing effects on the state of anxiety in humans. Copyright © 2011 Elsevier B.V. All rights reserved.

Sex-specific effects of developmental alcohol exposure on cocaine-induced place preference in adulthood.

PubMed

Macht, Victoria A; Kelly, Sandra J; Gass, Justin T

2017-08-14

Fetal Alcohol Syndrome (FAS) is associated with high rates of drug addiction in adulthood. One possible basis for increased drug use in this population is altered sensitivity to drug-associated contexts. This experiment utilized a rat model of FASD to examine behavioral and neural changes in the processing of drug cues in adulthood. Alcohol was given by intragastric intubation to pregnant rats throughout gestation and to rat pups during the early postnatal period (ET group). Controls consisted of a non-treated group (NC) and a pair-fed group given the intubation procedure without alcohol (IC). On postnatal day (PD) 90, rats from all treatment groups were given saline, 0.3mg/kg, 3.0mg/kg, or 10.0mg/kg cocaine pairings with a specific context in the conditioned place preference (CPP) paradigm. While control animals of both sexes showed cocaine CPP at the 3.0 and 10.0mg/kg doses, ET females also showed cocaine CPP at 0.3mg/kg. This was accompanied by a decrease in c-Fos/GAD 67 cells in the nucleus accumbens (NAc) shell and GAD 67 -only cells in the NAc shell and PFC at this 0.3mg/kg dose. ET males failed to show cocaine CPP at the 3.0mg/kg dose. This was associated with an increase in c-Fos only-labeled cells in the NAc core and PFC at this 3.0mg/kg dose. These results suggest that developmental alcohol exposure has a sexually-dimorphic effect on cocaine's conditioning effects in adulthood and the NAc. Copyright © 2017 Elsevier B.V. All rights reserved.

Nalmefene Reduces Reward Anticipation in Alcohol Dependence: An Experimental Functional Magnetic Resonance Imaging Study.

PubMed

Quelch, Darren R; Mick, Inge; McGonigle, John; Ramos, Anna C; Flechais, Remy S A; Bolstridge, Mark; Rabiner, Eugenii; Wall, Matthew B; Newbould, Rexford D; Steiniger-Brach, Björn; van den Berg, Franz; Boyce, Malcolm; Østergaard Nilausen, Dorrit; Breuning Sluth, Lasse; Meulien, Didier; von der Goltz, Christoph; Nutt, David; Lingford-Hughes, Anne

2017-06-01

Nalmefene is a µ and δ opioid receptor antagonist, κ opioid receptor partial agonist that has recently been approved in Europe for treating alcohol dependence. It offers a treatment approach for alcohol-dependent individuals with "high-risk drinking levels" to reduce their alcohol consumption. However, the neurobiological mechanism underpinning its effects on alcohol consumption remains to be determined. Using a randomized, double-blind, placebo-controlled, within-subject crossover design we aimed to determine the effect of a single dose of nalmefene on striatal blood oxygen level-dependent (BOLD) signal change during anticipation of monetary reward using the monetary incentive delay task following alcohol challenge. Twenty-two currently heavy-drinking, non-treatment-seeking alcohol-dependent males were recruited. The effect of single dose nalmefene (18 mg) on changes in a priori defined striatal region of interest BOLD signal change during reward anticipation compared with placebo was investigated using functional magnetic resonance imaging. Both conditions were performed under intravenous alcohol administration (6% vol/vol infusion to achieve a target level of 80 mg/dL). Datasets from 18 participants were available and showed that in the presence of the alcohol infusion, nalmefene significantly reduced the BOLD response in the striatal region of interest compared with placebo. Nalmefene did not alter brain perfusion. Nalmefene blunts BOLD response in the mesolimbic system during anticipation of monetary reward and an alcohol infusion. This is consistent with nalmefene's actions on opioid receptors, which modulate the mesolimbic dopaminergic system, and provides a neurobiological basis for its efficacy. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Dose-related effects of red wine and alcohol on hemodynamics, sympathetic nerve activity, and arterial diameter.

PubMed

Spaak, Jonas; Merlocco, Anthony C; Soleas, George J; Tomlinson, George; Morris, Beverley L; Picton, Peter; Notarius, Catherine F; Chan, Christopher T; Floras, John S

2008-02-01

The cardiovascular benefits of light to moderate red wine consumption often have been attributed to its polyphenol constituents. However, the acute dose-related hemodynamic, vasodilator, and sympathetic neural effects of ethanol and red wine have not been characterized and compared in the same individual. We sought to test the hypotheses that responses to one and two alcoholic drinks differ and that red wine with high polyphenol content elicits a greater effect than ethanol alone. Thirteen volunteers (24-47 yr; 7 men, 6 women) drank wine, ethanol, and water in a randomized, single-blind trial on three occasions 2 wk apart. One drink of wine and ethanol increased blood alcohol to 38 +/- 2 and 39 +/- 2 mg/dl, respectively, and two drinks to 72 +/- 4 and 83 +/- 3 mg/dl, respectively. Wine quadrupled plasma resveratrol (P < 0.001) and increased catechin (P < 0.03). No intervention affected blood pressure. One drink had no heart rate effect, but two drinks of wine increased heart rate by 5.7 +/- 1.6 beats/min; P < 0.001). Cardiac output fell 0.8 +/- 0.3 l/min after one drink of ethanol and wine (both P < 0.02) but increased after two drinks of ethanol (+0.8 +/- 0.3 l/min) and wine (+1.2 +/- 0.3 l/min) (P < 0.01). One alcoholic drink did not alter muscle sympathetic nerve activity (MSNA), while two drinks increased MSNA by 9-10 bursts/min (P < 0.001). Brachial artery diameter increased after both one and two alcoholic drinks (P < 0.001). No beverage augmented, and the second wine dose attenuated (P = 0.02), flow-mediated vasodilation. One drink of ethanol dilates the brachial artery without activating sympathetic outflow, whereas two drinks increase MSNA, heart rate, and cardiac output. These acute effects, which exhibit a narrow dose response, are not modified by red wine polyphenols.

[Effect of puerarin in myocardial protection in rats with acute and chronic alcoholism].

PubMed

Cui, Shu-qin

2011-12-01

To investigate the protective effect of puerarin on the myocardium of rats with acute and chronic alcoholism. In acute alcoholism experiment, normal male SD rats were randomly divided into the control group, alcoholism group and puerarin group (n=8), and high- and low-dose puerarin was administered. In chronic alcoholism experiment, increasing puerarin doses were given. Serum and myocardial levels of spartate aminotransferase (AST) and creatine phosphokinase (CPK) were determined using enzymatic methed, and superoxide dismutase (SOD), malondialdehyde (MDA), Ca(2+)-Mg(2+)-ATPase, and Na(+)-K(+)-ATPase in the myocardium were assayed with colorimetric method. HE staining was used to observe the microscopic changes of the myocardium. Compared with alcoholism group, puerarin-treated groups showed significantly lowered myocardial contents of MDA, CPK and AST and serum levels of AST and CPK (P<0.05, P<0.01) and increased myocardial SOD (P<0.05, P<0.01), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activity (P<0.05, P<0.01), but Na(+)-K(+)-ATPase was similar between the two groups (P>0.05). HE staining of the myocardium showed cell swelling and obscure cell boundaries in alcoholism group, especially in chronic alcoholism group. The myocardial structure in puerarin group remained clear and regular. Puerarin can protect from myocardial injuries induced by acute and chronic alcoholism in rats.

Effects of energy drinks mixed with alcohol on behavioral control: risks for college students consuming trendy cocktails.

PubMed

Marczinski, Cecile A; Fillmore, Mark T; Bardgett, Mark E; Howard, Meagan A

2011-07-01

There has been a dramatic rise in the consumption of alcohol mixed with energy drinks (AmED) in young people. AmED have been implicated in risky drinking practices and greater accidents and injuries have been associated with their consumption. Despite the increased popularity of these beverages (e.g., Red Bull and vodka), there is little laboratory research examining how the effects of AmED differ from alcohol alone. This experiment was designed to investigate if the consumption of AmED alters neurocognitive and subjective measures of intoxication compared with the consumption of alcohol alone. Participants (n=56) attended 1 session where they were randomly assigned to receive one of 4 doses (0.65 g/kg alcohol, 3.57 ml/kg energy drink, AmED, or a placebo beverage). Performance on a cued go/no-go task was used to measure the response of inhibitory and activational mechanisms of behavioral control following dose administration. Subjective ratings of stimulation, sedation, impairment, and level of intoxication were recorded. Alcohol alone impaired both inhibitory and activational mechanisms of behavioral control, as evidenced by increased inhibitory failures and increased response times compared to baseline performance. Coadministration of the energy drink with alcohol counteracted some of the alcohol-induced impairment of response activation, but not response inhibition. For subjective effects, alcohol increased ratings of stimulation, feeling the drink, liking the drink, impairment, and level of intoxication, and alcohol decreased the rating of ability to drive. Coadministration of the energy drink with alcohol increased self-reported stimulation, but resulted in similar ratings of the other subjective effects as when alcohol was administered alone. An energy drink appears to alter some of the objective and subjective impairing effects of alcohol, but not others. Thus, AmED may contribute to a high-risk scenario for the drinker. The mix of impaired behavioral inhibition and enhanced stimulation is a combination that may make AmED consumption riskier than alcohol consumption alone. Copyright © 2011 by the Research Society on Alcoholism.

Comparison of alcohol impairment of behavioral and attentional inhibition.

PubMed

Weafer, Jessica; Fillmore, Mark T

2012-11-01

Despite the wealth of studies demonstrating the impairing effects of alcohol on behavioral inhibition, less is known regarding effects of the drug on attentional inhibition (i.e., the ability to ignore distracting stimuli in the environment in order to focus attention on relevant information). The current study examined alcohol impairment of both behavioral and attentional inhibition, as well as potential associations between the two mechanisms of inhibitory control. Men (n=27) and women (n=21) performed a measure of behavioral inhibition (cued go/no-go task) and a measure of attentional inhibition (delayed ocular return task) following three doses of alcohol: 0.65 g/kg, 0.45 g/kg, and 0.0 g/kg (placebo). Alcohol impaired both behavioral and attentional inhibition relative to placebo; however, correlational analyses revealed no associations between measures of behavioral and attentional inhibition following any dose. Additionally, men committed more inhibitory failures on the behavioral inhibition task, whereas women committed more inhibitory failures on the attentional inhibition task. These findings suggest that behavioral and attentional inhibition are equally sensitive to the impairing effects of alcohol, yet represent distinct components of inhibitory control. Additionally, the observed gender differences in control of behavior and attention could have important implications regarding negative consequences associated with alcohol-induced disinhibition in men and women. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Alcohol consumption promotes mammary tumor growth and insulin sensitivity

PubMed Central

Hong, Jina; Holcomb, Valerie B.; Tekle, Samrawit A.; Fan, Betty; Núñez, Nomelí P.

2010-01-01

Epidemiological data show that in women, alcohol has a beneficial effect by increasing insulin sensitivity but also a deleterious effect by increasing breast cancer risk. These effects have not been shown concurrently in an animal model of breast cancer. Our objective is to identify a mouse model of breast cancer whereby alcohol increases insulin sensitivity and promotes mammary tumorigenesis. Our results from the glucose tolerance test and the homeostasis model assessment show that alcohol consumption improved insulin sensitivity. However, alcohol-consuming mice developed larger mammary tumors and developed them earlier than water-consuming mice. In vitro results showed that alcohol exposure increased the invasiveness of breast cancer cells in a dose-dependent manner. Thus, this animal model, an in vitro model of breast cancer, may be used to elucidate the mechanism(s) by which alcohol affects breast cancer. PMID:20202743

Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials.

PubMed

Krebs, Teri S; Johansen, Pål-Ørjan

2012-07-01

Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism have not been based on quantitative meta-analysis. Hence, we performed a meta-analysis of randomized controlled trials in order to evaluate the clinical efficacy of LSD in the treatment of alcoholism. Two reviewers independently extracted the data, pooling the effects using odds ratios (ORs) by a generic inverse variance, random effects model. We identified six eligible trials, including 536 participants. There was evidence for a beneficial effect of LSD on alcohol misuse (OR, 1.96; 95% CI, 1.36-2.84; p = 0.0003). Between-trial heterogeneity for the treatment effects was negligible (I² = 0%). Secondary outcomes, risk of bias and limitations are discussed. A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.

The role of salsolinol in alcohol intake and withdrawal.

PubMed

Clow, A; Topham, A; Saunders, J B; Murray, R; Sandler, M

1985-01-01

We studied the urinary excretion of the tetrahydroisoquinoline (TIQ) salsolinol, formed from acetaldehyde and dopamine, in both severely and moderately dependent alcoholics during withdrawal from alcohol and subsequent challenge with an acute dose of alcohol and L-dopa, and compared these results with controls. Plasma acetaldehyde and alcohol levels in a sub-population of severely dependent withdrawn alcoholic and control subjects following an acute dose of alcohol were also determined. Salsolinol excretion during the first 4 days of alcohol withdrawal was variable but 10 out of 14 alcoholics showed an increasing trend from day 1 to day 3 and 4 of alcohol withdrawal. L-dopa administration raised salsolinol excretion in controls and withdrawn alcoholics to a uniform extent. Loading of the withdrawn alcoholics with an acute dose of alcohol did not cause an increase in urinary salsolinol concentration (despite increased plasma acetaldehyde). Indeed, 24 h following acute alcohol administration, salsolinol excretion rates were depressed in the alcoholics but not in the controls.

Effects of Kaempferia parviflora extracts on reproductive parameters and spermatic blood flow in male rats.

PubMed

Chaturapanich, G; Chaiyakul, S; Verawatnapakul, V; Pholpramool, C

2008-10-01

Krachaidum (KD, Kaempferia parviflora Wall. Ex. Baker), a native plant of Southeast Asia, is traditionally used to enhance male sexual function. However, only few scientific data in support of this anecdote have been reported. The present study investigated the effects of feeding three different extracts of KD (alcohol, hexane, and water extracts) for 3-5 weeks on the reproductive organs, the aphrodisiac activity, fertility, sperm motility, and blood flow to the testis of male rats. Sexual performances (mount latency, mount frequency, ejaculatory latency, post-ejaculatory latency) and sperm motility were assessed by a video camera and computer-assisted sperm analysis respectively, while blood flow to the testis was measured by a directional pulsed Doppler flowmeter. The results showed that all extracts of KD had virtually no effect on the reproductive organ weights even after 5 weeks. However, administration of the alcohol extract at a dose of 70 mg/kg body weight (BW)/day for 4 weeks significantly decreased mount and ejaculatory latencies when compared with the control. By contrast, hexane and water extracts had no influence on any sexual behavior parameters. All types of extracts of KD had no effect on fertility or sperm motility. On the other hand, alcohol extract produced a significant increase in blood flow to the testis without affecting the heart rate and mean arterial blood pressure. In a separate study, an acute effect of alcohol extract of KD on blood flow to the testis was investigated. Intravenous injection of KD at doses of 10, 20, and 40 mg/kg BW caused dose-dependent increases in blood flow to the testis. The results indicate that alcohol extract of KD had an aphrodisiac activity probably via a marked increase in blood flow to the testis.

The effects of cocaine, alcohol and cocaine/alcohol combinations in conditioned taste aversion learning.

PubMed

Busse, Gregory D; Verendeev, Andrey; Jones, Jermaine; Riley, Anthony L

2005-09-01

We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.

Effects of Pregnancy and Nutritional Status on Alcohol Metabolism

PubMed Central

Shankar, Kartik; Ronis, Martin J.J.; Badger, Thomas M.

2007-01-01

Metabolism of alcohol (i.e., ethanol) is regulated by genetic and environmental factors as well as physiologic state. For a given alcohol intake, the rate of alcohol clearance, which ultimately determines tissue ethanol concentrations, may be the most significant risk factor for many of the detrimental effects of alcohol. Faster ethanol clearance would help minimize target tissue concentrations, and in pregnant women, mitigate fetal alcohol exposure. Much remains to be known about the effects of the altered endocrine milieu of pregnancy on alcohol metabolism and clearance in the mother. Research has shown that among pregnant rats allowed unrestricted access to alcohol and those fed alcohol containing liquid diets under experimental conditions via a feeding tube (total enteral nutrition [TEN]), urine ethanol concentrations (and thus blood and tissue ethanol concentrations) are lower in pregnant rats compared with non-pregnant females given the same dose of ethanol. Maternal nutritional status also is an important determinant of fetal alcohol toxicity. Research using the TEN system has demonstrated that alcohol-induced fetal growth retardation is potentiated by undernutrition in part via impaired alcohol metabolism and clearance. PMID:17718402

Effects of energy drinks mixed with alcohol on behavioral control: Risks for college students consuming trendy cocktails

PubMed Central

Marczinski, Cecile A.; Fillmore, Mark T.; Bardgett, Mark E.; Howard, Meagan A.

2011-01-01

Background There has been a dramatic rise in the consumption of alcohol mixed with energy drinks (AmED) in young people. AmEDs have been implicated in risky drinking practices and greater accidents and injuries have been associated with their consumption. Despite the increased popularity of these beverages (e.g., Red Bull and vodka), there is little laboratory research examining how the effects of AmED differ from alcohol alone. This experiment was designed to investigate if the consumption of AmED alters neurocognitive and subjective measures of intoxication compared with the consumption of alcohol alone. Methods Participants (n=56) attended one session where they were randomly assigned to receive one of four doses (0.65 g/kg alcohol, 3.57 ml/kg energy drink, AmED or a placebo beverage). Performance on a cued go/no-go task was used to measure the response of inhibitory and activational mechanisms of behavioral control following dose administration. Subjective ratings of stimulation, sedation, impairment and level of intoxication were recorded. Results Alcohol alone impaired both inhibitory and activational mechanisms of behavioral control, as evidenced by increased inhibitory failures and increased response times compared to baseline performance. Coadministration of the energy drink with alcohol counteracted some of the alcohol-induced impairment of response activation, but not response inhibition. For subjective effects, alcohol increased ratings of stimulation, feeling the drink, liking the drink, impairment and level of intoxication and alcohol decreased the rating of ability to drive. Coadministration of the energy drink with alcohol increased self-reported stimulation, but resulted in similar ratings of the other subjective effects as when alcohol was administered alone. Conclusions An energy drink appears to alter some of alcohol’s objective and subjective impairing effects, but not others. Thus AmEDs may contribute to a high risk scenario for the drinker. The mix of impaired behavioral inhibition and enhanced stimulation is a combination that may make AmED consumption riskier than alcohol consumption alone. PMID:21676002

Levetiracetam for the treatment of alcohol withdrawal syndrome: a multicenter, prospective, randomized, placebo-controlled trial.

PubMed

Richter, Christoph; Hinzpeter, Axel; Schmidt, Folkhard; Kienast, Thorsten; Preuss, Ulrich W; Plenge, Thomas; Heinz, Andreas; Schaefer, Martin

2010-12-01

Treatment of alcohol withdrawal syndrome (AWS) with benzodiazepines is limited by risk of abuse, intoxication, respiratory problems, and liver toxicity. Alternatives such as carbamazepine and valproate may also have safety problems, such as hepatotoxicity or central nervous adverse effects. We therefore investigated the safety and efficacy of levetiracetam (LV), a newer antiepileptic with a potentially favorable adverse-effect profile, for the treatment of AWS. One hundred six patients were enrolled in a prospective, randomized, double-blind, multicenter, placebo-controlled trial. Levetiracetam was administered in a fixed dose schedule over 6 days. Diazepam was added when symptom triggered as rescue medication. Severity of the AWS was measured with the AWS and Clinical Institute Withdrawal Assessment Scale. Although tolerability and safety data were similar in the LV group when compared with placebo, the total daily and weekly dose of diazepam as rescue medication and the severity of alcohol withdrawal symptoms did not differ significantly between groups. Our data so far do not support an additional effect of LV on the reduction of alcohol withdrawal symptoms.

Effect on gastric function and symptoms of drinking wine, black tea, or schnapps with a Swiss cheese fondue: randomised controlled crossover trial.

PubMed

Heinrich, Henriette; Goetze, Oliver; Menne, Dieter; Iten, Peter X; Fruehauf, Heiko; Vavricka, Stephan R; Schwizer, Werner; Fried, Michael; Fox, Mark

2010-12-14

To compare the effects of drinking white wine or black tea with Swiss cheese fondue followed by a shot of cherry schnapps on gastric emptying, appetite, and abdominal symptoms. Randomised controlled crossover study. 20 healthy adults (14 men) aged 23-58. Cheese fondue (3260 kJ, 32% fat) labelled with 150 mg sodium (13)Carbon-octanoate was consumed with 300 ml of white wine (13%, 40 g alcohol) or black tea in randomised order, followed by 20 ml schnapps (40%, 8 g alcohol) or water in randomised order. Cumulative percentage dose of (13)C substrate recovered over four hours (higher values indicate faster gastric emptying) and appetite and dyspeptic symptoms (visual analogue scales). Gastric emptying was significantly faster when fondue was consumed with tea or water than with wine or schnapps (cumulative percentage dose of (13)C recovered 18.1%, 95% confidence interval 15.2% to 20.9% v 7.4%, 4.6% to 10.3%; P<0.001). An inverse dose-response relation between alcohol intake and gastric emptying was evident. Appetite was similar with consumption of wine or tea (difference 0.11, -0.12 to 0.34; P=0.35), but reduced if both wine and schnapps were consumed (difference -0.40, -0.01 to -0.79; P<0.046). No difference in dyspeptic symptoms was present. Gastric emptying after a Swiss cheese fondue is noticeably slower and appetite suppressed if consumed with higher doses of alcohol. This effect was not associated with dyspeptic symptoms. ClinicalTrials.gov NCT00943696.

Alcohol and caffeine consumption and decreased fertility.

PubMed

Hakim, R B; Gray, R H; Zacur, H

1998-10-01

To examine the effects of alcohol and caffeine on conception. Prospective observational study. Healthy volunteers in two manufacturing facilities. One hundred twenty-four women who provided daily urine samples for measurement of steroid hormones and hCG, and prospective information about alcohol and caffeine consumption. Probability of conception per 100 menstrual cycles. There was >50% reduction in the probability of conception during a menstrual cycle during which participants consumed alcohol. Caffeine consumption did not independently affect the probability of conception but may enhance alcohol's negative effect. Women who abstained from alcohol and consumed less than one cup of coffee or its equivalent per day conceived 26.9 pregnancies per 100 menstrual cycles compared with 10.5 per 100 menstrual cycles among those who consumed any alcohol and more than one cup of coffee per day. This study revealed an independent dose-related negative effect of alcohol consumption on the ability to conceive. Our results suggest that women who are attempting to conceive should abstain from consuming alcohol.

Bone-97 Alcohol and Skeletal Adaptation to Mechanical Usage.

DTIC Science & Technology

1999-10-01

dose response and time course effects of administered ethanol (Tasks 1 and 2) on blood alcohol levels, serum chemistry and bone metabolism...evaluation of the long-term skeletal effects of ethanol on bone metabolism and strength (Task 4); determination of the effects of ethanol on the skeletal...adaptation resistance exercise training (Task 5); determination of the effects of prior consumption of ethanol or PTH-induced increases in mRNA

A comparison of the central nervous system effects of alcohol at pseudo-steady state in Caucasian and expatriate Japanese healthy male volunteers.

PubMed

Zoethout, Remco W M; de Kam, Marieke L; Dahan, Albert; Cohen, Adam F; van Gerven, Joop M A

2012-11-01

In general, Japanese and Caucasians differ in their response to alcohol. To investigate these differences the alcohol clamping method can be used. This strictly controlled infusion regimen provides a reliable tool to study contrasts in central nervous system (CNS) effects and/or alcohol disposition. In this study, twelve Japanese and twelve Caucasian healthy volunteers received two concentrations of intravenous alcohol or placebo using the alcohol clamp. Infusion rates during the steady state phase were used to compare alcohol clearance between the subgroups. Central nervous system (CNS) effects were frequently measured throughout the clamp. On average, significantly lower amounts of alcohol were needed to maintain similar stable concentrations in the Japanese group. However, these differences disappeared when values were corrected for lean body mass. The most pronounced pharmacodynamic differences between the groups were observed on body sway and on the visual analogue scale for subjective alcohol effects, mainly at the highest dose level. The alcohol clamp seems a useful method to compare differences in alcohol metabolism between groups. Some CNS effects of alcohol differed clearly between Japanese and Caucasians, but others did not, even though alcohol levels were stable and similar between the two groups. Copyright © 2012 Elsevier Inc. All rights reserved.

Alcohol Dose Effects on Brain Circuits During Simulated Driving: An fMRI Study

PubMed Central

Meda, Shashwath A.; Calhoun, Vince D.; Astur, Robert S.; Turner, Beth M.; Ruopp, Kathryn; Pearlson, Godfrey D.

2009-01-01

Driving while intoxicated remains a major public health hazard. Driving is a complex task involving simultaneous recruitment of multiple cognitive functions. The investigators studied the neural substrates of driving and their response to different blood alcohol concentrations (BACs), using functional magnetic resonance imaging (fMRI) and a virtual reality driving simulator. We used independent component analysis (ICA) to isolate spatially independent and temporally correlated driving-related brain circuits in 40 healthy, adult moderate social drinkers. Each subject received three individualized, separate single-blind doses of beverage alcohol to produce BACs of 0.05% (moderate), 0.10% (high), or 0% (placebo). 3 T fMRI scanning and continuous behavioral measurement occurred during simulated driving. Brain function was assessed and compared using both ICA and a conventional general linear model (GLM) analysis. ICA results replicated and significantly extended our previous 1.5T study (Calhoun et al. [2004a]: Neuropsychopharmacology 29:2097–2017). GLM analysis revealed significant dose-related functional differences, complementing ICA data. Driving behaviors including opposite white line crossings and mean speed independently demonstrated significant dose-dependent changes. Behavior-based factors also predicted a frontal-basal-temporal circuit to be functionally impaired with alcohol dosage across baseline scaled, good versus poorly performing drivers. We report neural correlates of driving behavior and found dose-related spatio-temporal disruptions in critical driving-associated regions including the superior, middle and orbito frontal gyri, anterior cingulate, primary/supplementary motor areas, basal ganglia, and cerebellum. Overall, results suggest that alcohol (especially at high doses) causes significant impairment of both driving behavior and brain functionality related to motor planning and control, goal directedness, error monitoring, and memory. PMID:18571794

Alcohol and Caffeine: The Perfect Storm

PubMed Central

O'Brien, Mary Claire

2011-01-01

Although it is widely believed that caffeine antagonizes the intoxicating effects of alcohol, the molecular mechanisms underlying their interaction are incompletely understood. It is known that both caffeine and alcohol alter adenosine neurotransmission, but the relationship is complex, and may be dose dependent. In this article, we review the available literature on combining caffeine and alcohol. Ethical constraints prohibit laboratory studies that would mimic the high levels of alcohol intoxication achieved by many young people in real-world settings, with or without the addition of caffeine. We propose a possible neurochemical mechanism for the increase in alcohol consumption and alcohol-related consequences that have been observed in persons who simultaneously consume caffeine. Caffeine is a nonselective adenosine receptor antagonist. During acute alcohol intake, caffeine antagonizes the “unwanted” effects of alcohol by blocking the adenosine A1 receptors that mediate alcohol's somnogenic and ataxic effects. The A1 receptor–mediated “unwanted” anxiogenic effects of caffeine may be ameliorated by alcohol-induced increase in the extracellular concentration of adenosine. Moreover, by means of interactions between adenosine A2A and dopamine D2 receptors, caffeine-mediated blockade of adenosine A2A receptors can potentiate the effects of alcohol-induced dopamine release. Chronic alcohol intake decreases adenosine tone. Caffeine may provide a “treatment” for the withdrawal effects of alcohol by blocking the effects of upregulated A1 receptors. Finally, blockade of A2A receptors by caffeine may contribute to the reinforcing effects of alcohol. PMID:24761263

Alcohol-impaired speed and accuracy of cognitive functions: a review of acute tolerance and recovery of cognitive performance.

PubMed

Schweizer, Tom A; Vogel-Sprott, Muriel

2008-06-01

Much research on the effects of a dose of alcohol has shown that motor skills recover from impairment as blood alcohol concentrations (BACs) decline and that acute tolerance to alcohol impairment can develop during the course of the dose. Comparable alcohol research on cognitive performance is sparse but has increased with the development of computerized cognitive tasks. This article reviews the results of recent research using these tasks to test the development of acute tolerance in cognitive performance and recovery from impairment during declining BACs. Results show that speed and accuracy do not necessarily agree in detecting cognitive impairment, and this mismatch most frequently occurs during declining BACs. Speed of cognitive performance usually recovers from impairment to drug-free levels during declining BACs, whereas alcohol-increased errors fail to diminish. As a consequence, speed of cognitive processing tends to develop acute tolerance, but no such tendency is shown in accuracy. This "acute protracted error" phenomenon has not previously been documented. The findings pose a challenge to the theory of alcohol tolerance on the basis of physiological adaptation and raise new research questions concerning the independence of speed and accuracy of cognitive processes, as well as hemispheric lateralization of alcohol effects. The occurrence of alcohol-induced protracted cognitive errors long after speed returned to normal is identified as a potential threat to the safety of social drinkers that requires urgent investigation.

Protective effect of co-administration of curcumin and sildenafil in alcohol induced neuropathy in rats.

PubMed

Kaur, Maninder; Singh, Amarjeet; Kumar, Bimlesh; Singh, Sachin Kumar; Bhatia, Amit; Gulati, Monica; Prakash, T; Bawa, Palak; Malik, Adil Hussain

2017-06-15

Neuropathic pain associated with chronic alcohol consumption is a medico-socioeconomical problem that affects both central and peripheral nervous system and has no satisfactory treatment till date. The present study was designed to investigate the protective effect of co-administration of curcumin and sildenafil on alcohol induced neuropathic pain in rats. In order to carry out this, ethanol (35% v/v, 10g/kg, p.o.) was administered for 10 weeks to induce neuropathic pain. Curcumin (30 and 60mg/kg, i.p.) and sildenafil (5 and 10mg/kg, i.p.) were given alone and in combination at their lower doses (30mg/kg curcumin and 5mg/kg, sildenafil, i.p.) to investigate the changes in thermal and mechanical hyperalgesia, allodynia and histopathological parameters. Biochemical estimations of thiobarbituric acid reactive species, glutathione and protein was also carried out to evaluate oxidative stress. The results revealed that chronic alcohol consumption for 10 weeks caused significant thermal and mechanical hyperalgesia, allodynia and increased oxidative stress. Individual administration of both the drugs at their low as well as high doses were able to improve the symptoms of alcohol induced neuropathic pain. Whereas co-administration of curcumin and sildenafil at their lower doses itself were found to significantly improve nerve functions, biochemical and histopathological parameters as compared to their individual administration. It is therefore proposed that co-administration of curcumin and sildenafil may bring new dimension towards attenuation of alcohol induced neuropathic pain affecting central as well as peripheral nervous system. Copyright © 2017 Elsevier B.V. All rights reserved.

Moderate prenatal alcohol exposure alters behavior and neuroglial parameters in adolescent rats.

PubMed

Brolese, Giovana; Lunardi, Paula; Broetto, Núbia; Engelke, Douglas S; Lírio, Franciane; Batassini, Cristiane; Tramontina, Ana Carolina; Gonçalves, Carlos-Alberto

2014-08-01

Alcohol consumption by women during gestation has become increasingly common. Although it is widely accepted that exposure to high doses of ethanol has long-lasting detrimental effects on brain development, the case for moderate doses is underappreciated, and benchmark studies have demonstrated structural and behavioral defects associated with moderate prenatal alcohol exposure in humans and animal models. This study aimed to investigate the influence of in utero exposure to moderate levels of ethanol throughout pregnancy on learning/memory, anxiety parameters and neuroglial parameters in adolescent offspring. Female rats were exposed to an experimental protocol throughout gestation up to weaning. After mating, the dams were divided into three groups and treated with only water (control), non-alcoholic beer (vehicle) or 10% (vv) beer solution (moderate prenatal alcohol exposure - MPAE). Adolescent male offspring were subjected to the plus-maze discriminative avoidance task to evaluate learning/memory and anxiety-like behavior. Hippocampi were dissected and slices were obtained for immunoquantification of GFAP, NeuN, S100B and the NMDA receptor. The MPAE group clearly presented anxiolytic-like behavior, even though they had learned how to avoid the aversive arm. S100B protein was increased in the cerebrospinal fluid (CSF) in the group treated with alcohol, and alterations in GFAP expression were also shown. This study indicates that moderate ethanol doses administered during pregnancy could induce anxiolytic-like effects, suggesting an increase in risk-taking behavior in adolescent male offspring. Furthermore, the data show the possibility that glial cells are involved in the altered behavior present after prenatal ethanol treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Application of a computational decision model to examine acute drug effects on human risk taking.

PubMed

Lane, Scott D; Yechiam, Eldad; Busemeyer, Jerome R

2006-05-01

In 3 previous experiments, high doses of alcohol, marijuana, and alprazolam acutely increased risky decision making by adult humans in a 2-choice (risky vs. nonrisky) laboratory task. In this study, a computational modeling analysis known as the expectancy valence model (J. R. Busemeyer & J. C. Stout, 2002) was applied to individual-participant data from these studies, for the highest administered dose of all 3 drugs and corresponding placebo doses, to determine changes in decision-making processes that may be uniquely engendered by each drug. The model includes 3 parameters: responsiveness to rewards and losses (valence or motivation); the rate of updating expectancies about the value of risky alternatives (learning/memory); and the consistency with which trial-by-trial choices match expected outcomes (sensitivity). Parameter estimates revealed 3 key outcomes: Alcohol increased responsiveness to risky rewards and decreased responsiveness to risky losses (motivation) but did not alter expectancy updating (learning/memory); both marijuana and alprazolam produced increases in risk taking that were related to learning/memory but not motivation; and alcohol and marijuana (but not alprazolam) produced more random response patterns that were less consistently related to expected outcomes on the 2 choices. No significant main effects of gender or dose by gender interactions were obtained, but 2 dose by gender interactions approached significance. These outcomes underscore the utility of using a computational modeling approach to deconstruct decision-making processes and thus better understand drug effects on risky decision making in humans.

Women's drinking decisions in sexually risky situations: Effects of a low level of intoxication.

PubMed

Noel, Nora E; Daniels, Karen A; Ogle, Richard L; Maisto, Stephen A; Lee A, Jackson; Ehlke, Sarah J; Carroll, Mallorie G

2015-08-01

Alcohol administration studies assessing alcohol's deleterious effects on women's threat perception and response in potential sexual assault situations usually employ a moderate to high dose (.07% BAC or more) and measure alcohol's effects specifically on women's sexual decisions. The current study used a low dose (.03%, equivalent to about 1-2 drinks) to assess women's projected decisions on a different risky behavior: decisions to continue drinking and to drink higher amounts in a series of ecologically-valid sexual risk situations. Young adult women (n=17; M age=21.8, SD=1.3, range 21-25) participated in a three-session double-blind within subjects 2 (type of scenario)×3( beverage) experiment, responding each time to 6 vignettes with an attractive man who was either Familiar or had Just Met her. In each session participants consumed a beverage (alcohol, placebo or water, random order) and projected emotional reactions and drinking decisions (likelihood and amount) in each of the 6 scenarios. Regardless of beverage, women predicted greater happiness, drinking likelihood, and drinking amount with "Familiar" men. However, there was also an interaction: they projected increased subsequent amounts in the .03% BAC (vs. water and placebo) condition differentially in the "Familiar" scenarios. When the woman is Familiar with the man in a risky sexual situation, just one drink may increase subsequent projected alcohol amount over that originally intended. Implications include a low dose as a possible prime for more drinking, increasing sexual assault risk. Copyright © 2015 Elsevier Ltd. All rights reserved.

Alcohol and Group Formation: A Multimodal Investigation of the Effects of Alcohol on Emotion and Social Bonding

PubMed Central

Sayette, Michael A.; Creswell, Kasey G.; Dimoff, John D.; Fairbairn, Catharine E.; Cohn, Jeffrey F.; Heckman, Bryan W.; Kirchner, Thomas R.; Levine, John M.; Moreland, Richard L.

2017-01-01

We integrated research on emotion and on small groups to address a fundamental and enduring question facing alcohol researchers: What are the specific mechanisms that underlie the reinforcing effects of drinking? In one of the largest alcohol-administration studies yet conducted, we employed a novel group-formation paradigm to evaluate the socioemotional effects of alcohol. Seven hundred twenty social drinkers (360 male, 360 female) were assembled into groups of 3 unacquainted persons each and given a moderate dose of an alcoholic, placebo, or control beverage, which they consumed over 36 min. These groups’ social interactions were video recorded, and the duration and sequence of interaction partners’ facial and speech behaviors were systematically coded (e.g., using the Facial Action Coding System). Alcohol consumption enhanced individual- and group-level behaviors associated with positive affect, reduced individual-level behaviors associated with negative affect, and elevated self-reported bonding. Our results indicate that alcohol facilitates bonding during group formation. Assessing nonverbal responses in social contexts offers new directions for evaluating the effects of alcohol. PMID:22760882

Impact of adolescent alcohol use across the lifespan: Long-lasting tolerance to high-dose alcohol coupled with potentiated spatial memory impairments to moderate-dose alcohol.

PubMed

Matthews, Douglas B; Novier, Adelle; Diaz-Granados, Jaime L; Van Skike, Candice E; Ornelas, Laura; Mittleman, G

2017-06-01

Understanding how alcohol exposure during adolescence affects aging is a critical but understudied area. In the present study, male rats were exposed to either alcohol or saline during adolescence, then tested every 4 months following either an ethanol or saline challenge; animals were tested until postnatal day (PD) 532. It was found that long-lasting tolerance to high-dose ethanol exists through the test period, as measured by loss of righting reflex, while tolerance to lower doses of ethanol is not found. In addition, alcohol exposure during adolescence facilitated spatial memory impairments to acute ethanol challenges later in life. The current work demonstrates that exposure to ethanol during adolescent development can produce long-lasting detrimental impairments. Copyright © 2017 Elsevier Inc. All rights reserved.

Stimulant and motivational effects of alcohol: lessons from rodent and primate models.

PubMed

Brabant, Christian; Guarnieri, Douglas J; Quertemont, Etienne

2014-07-01

In several animal species including humans, the acute administration of low doses of alcohol increases motor activity. Different theories have postulated that alcohol-induced hyperactivity is causally related to alcoholism. Moreover, a common biological mechanism in the mesolimbic dopamine system has been proposed to mediate the stimulant and motivational effects of alcohol. Numerous studies have examined whether alcohol-induced hyperactivity is related to alcoholism using a great variety of animal models and several animal species. However, there is no review that has summarized this extensive literature. In this article, we present the various experimental models that have been used to study the relationship between the stimulant and motivational effects of alcohol in rodents and primates. Furthermore, we discuss whether the theories hypothesizing a causal link between alcohol-induced hyperactivity and alcoholism are supported by published results. The reviewed findings indicate that animal species that are stimulated by alcohol also exhibit alcohol preference. Additionally, the role of dopamine in alcohol-induced hyperactivity is well established since blocking dopaminergic activity suppresses the stimulant effects of alcohol. However, dopamine transmission plays a much more complex function in the motivational properties of alcohol and the neuronal mechanisms involved in alcohol stimulation and reward are distinct. Overall, the current review provides mixed support for theories suggesting that the stimulant effects of alcohol are related to alcoholism and highlights the importance of animal models as a way to gain insight into alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

Alcohol's Effects on the Cardiovascular System.

PubMed

Piano, Mariann R

2017-01-01

Alcohol use has complex effects on cardiovascular (CV) health. The associations between drinking and CV diseases such as hypertension, coronary heart disease, stroke, peripheral arterial disease, and cardiomyopathy have been studied extensively and are outlined in this review. Although many behavioral, genetic, and biologic variants influence the interconnection between alcohol use and CV disease, dose and pattern of alcohol consumption seem to modulate this most. Low-to-moderate alcohol use may mitigate certain mechanisms such as risk and hemostatic factors affecting atherosclerosis and inflammation, pathophysiologic processes integral to most CV disease. But any positive aspects of drinking must be weighed against serious physiological effects, including mitochondrial dysfunction and changes in circulation, inflammatory response, oxidative stress, and programmed cell death, as well as anatomical damage to the CV system, especially the heart itself. Both the negative and positive effects of alcohol use on particular CV conditions are presented here. The review concludes by suggesting several promising avenues for future research related to alcohol use and CV disease. These include using direct biomarkers of alcohol to confirm self-report of alcohol consumption levels; studying potential mediation of various genetic, socioeconomic, and racial and ethnic factors that may affect alcohol use and CV disease; reviewing alcohol-medication interactions in cardiac patients; and examining CV effects of alcohol use in young adults and in older adults.

Genotypic and sex differences in anxiety-like behavior and alcohol-induced anxiolysis in High Drinking in the Dark selected mice.

PubMed

Barkley-Levenson, Amanda M; Crabbe, John C

2015-02-01

Alcohol use disorders and anxiety disorders are highly comorbid in humans. In rodent lines selected for alcohol drinking, differences in anxiety-like behavior are also seen. The High Drinking in the Dark (HDID) lines of mice are selectively bred for drinking to intoxication during limited access to alcohol, and these mice represent a genetic model of risk for binge-like drinking. The present studies investigated whether these selected lines differ from control (HS) mice in basal anxiety behavior or in anxiolytic response to alcohol. We also assessed the genetic correlation between alcohol drinking in the dark (DID) and basal anxiety-like behavior using existing inbred strain data. Mice of both sexes and HDID replicates (HDID-1 and HDID-2) were tested on an elevated zero maze immediately following a DID test. In general, HDID mice showed more time spent in the open arms after drinking alcohol than HS mice, and open-arm time was significantly correlated with blood alcohol concentration. HDID-1 male mice also showed less anxiety-like behavior at baseline (water-drinking controls). In a separate experiment, HDID-1 and HS mice were tested for anxiolytic dose-response to acute alcohol injections. Both genotypes showed increasing time spent in the open arms with increasing alcohol doses, and HDID-1 and female mice had greater open-arm time across all doses. HDID-1 control males showed lower anxiety-like behavior than the HS control males. Inbred strain data analysis also showed no significant genetic relationship between alcohol DID and anxiety. These findings suggest that HDID selection has not produced systematic changes in anxiety-like behavior or sensitivity to alcohol-induced anxiolysis, though there is a tendency in the male mice of the first replicate toward reduced basal anxiety-like behavior. Therefore, anxiety state and sensitivity to alcohol's anxiolytic effects do not appear to contribute significantly to the high drinking behavior of the HDID mice. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of the cognitive, psychomotor and pharmacokinetic profiles of rupatadine, hydroxyzine and cetirizine, in combination with alcohol, in healthy volunteers.

PubMed

Barbanoj, Manuel J; García-Gea, Consuelo; Antonijoan, Rosa; Izquierdo, Iñaki; Donado, Ester; Pérez, Iñaki; Solans, Anna; Jané, Francesc

2006-01-01

The Central Nervous System (CNS) impairment induced by moderate alcohol (ALC) ingestion may be enhanced if other drugs are taken simultaneously. Rupatadine (RUP) is a new H(1)-antihistamine which also inhibits platelet activating factor (PAF) release in inflammatory reactions. The main aim of the study was to assess the effects of ALC 0.8 g/Kg on RUP (10 mg and 20 mg) CNS effects. An evaluation of alcohol and RUP pharmacokinetics was also attained. Eighteen healthy young volunteers of both sexes participated in a phase I, randomised, crossover, double-blind, placebo-controlled study. At 2-week intervals they received six treatments: (a) placebo (PLA), (b) ALC alone and ALC in combination with: (c) hydroxyzine 25 mg (HYD), (d) cetirizine 10 mg (CET), (e) RUP 10 mg or (f) RUP 20 mg. At baseline and several times thereafter, seven psychomotor performance tests (finger tapping, fine motoric skills, nystagmus, temporal estimation, critical-flicker-fusion frequency, 'd2' cancellation, simple reaction) and eleven subjective self-reports (drunkenness, sleepiness, alertness, clumsiness, anger, inattentiveness, efficiency, happiness, hostility, interest and extraversion) were carried out. Two-way (treatment, time) ANOVAs for repeated measures to each variable together with a multivariate non-parametric approach were applied. Plasma concentrations of alcohol, and of RUP and its metabolites, were quantified by validated immunofluorescence and LC/MS/MS methods, respectively. Plasma-time curves for all compounds were analysed by means of model-independent methods. The combination of alcohol with HYD, CET and RUP 20 mg produced more cognitive and psychomotor impairment as compared to alcohol alone, being the combination of alcohol and HYD the one which induced the greatest deterioration. The combination of alcohol and RUP 10 mg could not be differentiated from ALC alone. Subjective self-reports reflect effects on metacognition after the combination of alcohol with HYD and CET i.e. the increased objective impairment observed was not subjectively perceived by the subjects. No significant differences were obtained when comparing alcohol plasma concentrations assessed after the treatments evaluated. RUP showed a lineal kinetic relationship after 10 and 20 mg with a higher exposition to both metabolites assayed. Present results showed that single oral doses of rupatadine 10 mg in combination with alcohol do not produce more cognitive and psychomotor impairment than alcohol alone. Higher doses of rupatadine, in combination with alcohol, may induce cognitive and psychomotor deterioration as hydroxyzine and cetirizine at therapeutic doses.

Chronic alcoholism increases the induction dose of propofol.

PubMed

Liang, C; Chen, J; Gu, W; Wang, H; Xue, Z

2011-10-01

The present study was designed to investigate the possible effect of chronic alcohol intake on propofol and remifentanil requirements, which was determined by quantifying the 50% (EC(50) ) and 95% (EC(95) ) effective effect-site concentrations for propofol and remifentanil at loss of consciousness (LOC) and after a painful stimulus. Thirty male patients (alcoholic group; n = 30) with chronic alcoholism and 30 patients (control group; n = 30) with a history of small alcohol intake were anaesthetized with propofol and remifentanil by target-controlled infusion. The predicted drug concentrations and Bispectral Index (BIS) values were recorded at LOC and after no response to painful stimuli. The EC(50) and EC(95) of propofol at LOC in alcoholic group were 3.15 [95% confidence interval (CI), 2.77-3.37] and 4.05 (95% CI, 3.18-5.26) μg/ml, respectively, and those of the control group were 2.21 (95% CI, 1.92-2.86) and 3.04 (95% CI, 2.45-4.64) μg/ml, respectively. The EC(50) and EC(95) of remifentanil measured after no response to painful stimuli in the alcoholic group were 3.02 (95% CI, 2.70-3.38) and 4.98 (95% CI, 4.56-5.89) ng/ml, respectively, and those of the control group were 2.95 (95% CI, 2.68-3.33) and 4.86 (95% CI, 4.55-5.92) ng/ml, respectively. The EC(50) and EC(95) values of propofol at LOC in the control group were significantly lower than that of the alcoholic group. These findings suggest that the induction dose requirements of propofol are increased in alcoholic patients anaesthetized with propofol and remifentanil administered by target controlled infusion. 2011 The Authors Acta Anaesthesiologica Scandinavica, 2011 The Acta Anaesthesiologica Scandinavica Foundation.

Faster Self-paced Rate of Drinking for Alcohol Mixed with Energy Drinks versus Alcohol Alone

PubMed Central

Marczinski, Cecile A.; Fillmore, Mark T.; Maloney, Sarah F.; Stamates, Amy L.

2016-01-01

The consumption of alcohol mixed with energy drinks (AmED) has been associated with higher rates of binge drinking and impaired driving when compared to alcohol alone. However, it remains unclear why the risks of use of AmED are heightened compared to alcohol alone even when the doses of alcohol consumed are similar. Therefore, the purpose of this laboratory study was to investigate if the rate of self-paced beverage consumption was faster for a dose of AmED versus alcohol alone using a double-blind, within-subjects, placebo-controlled study design. Participants (n = 16) of equal gender who were social drinkers attended 4 separate test sessions that involved consumption of alcohol (1.97 ml/kg vodka) and energy drinks, alone and in combination. On each test day, the dose assigned was divided into 10 cups. Participants were informed that they would have a two hour period to consume the 10 drinks. After the self-paced drinking period, participants completed a cued go/no-go reaction time task and subjective ratings of stimulation and sedation. The results indicated that participants consumed the AmED dose significantly faster (by approximately 16 minutes) than the alcohol dose. For the performance task, participants’ mean reaction times were slower in the alcohol conditions and faster in the energy drink conditions. In conclusion, alcohol consumers should be made aware that rapid drinking might occur for AmED beverages thus heightening alcohol-related safety risks. The fast rate of drinking may be related to the generalized speeding of responses following energy drink consumption. PMID:27819431

A PC-based software test for measuring alcohol and drug effects in human subjects.

PubMed

Mills, K C; Parkman, K M; Spruill, S E

1996-12-01

A new software-based visual search and divided-attention test of cognitive performance was developed and evaluated in an alcohol dose-response study with 24 human subjects aged 21-62 years. The test used language-free, color, graphic displays to represent the visuospatial demands of driving. Cognitive demands were increased over previous hardware-based tests, and the motor skills required for the test involved minimal eye movements and eye-hand coordination. Repeated performance on the test was evaluated with a latin-square design by using a placebo and two alcohol doses, low (0.48 g/kg/LBM) and moderate (0.72 g/kg/LBM). The data on 7 females and 17 males yielded significant falling and rising impairment effects coincident with moderate rising and falling breath alcohol levels (mean peak BrALs = 0.045 g/dl and 0.079 g/dl). None of the subjects reported eye-strain or psychomotor fatigue as compared with previous tests. The high sensitivity/variance relative to use in basic and applied research, and worksite fitness-for-duty testing, was discussed. The most distinct advantage of a software-based test that operates on readily available PCs is that it can be widely distributed to researchers with a common reference to compare a variety of alcohol and drug effects.

Comparison of the effect of the GABAB receptor agonist, baclofen, and the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in three different lines of alcohol-preferring rats

PubMed Central

Maccioni, Paola; Zaru, Alessandro; Loi, Barbara; Lobina, Carla; Carai, Mauro A.M.; Gessa, Gian Luigi; Capra, Alessandro; Mugnaini, Claudia; Pasquini, Serena; Corelli, Federico; Hyytiä, Petri; Lumeng, Lawrence; Colombo, Giancarlo

2012-01-01

Background Administration of the GABAB receptor agonist, baclofen, and positive allosteric modulator (PAM), GS39783, has been repeatedly reported to suppress multiple alcohol-related behaviors, including operant oral alcohol self-administration, in rats. The present study was designed to compare the effect of baclofen and GS39783 on alcohol self-administration in three lines of selectively bred, alcohol-preferring rats: Indiana alcohol-preferring (P), Sardinian alcohol-preferring (sP), and Alko Alcohol (AA). Methods Rats of each line were initially trained to respond on a lever, on a fixed ratio (FR) 4 (FR4) schedule of reinforcement, to orally self-administer alcohol (15%, v/v) in daily 30-min sessions. Once responding reached stable levels, rats were exposed to a sequence of experiments testing baclofen (0, 1, 1.7, and 3 mg/kg; i.p.) and GS39783 (0, 25, 50, and 100 mg/kg; i.g.) on FR4 and progressive ratio (PR) schedules of reinforcement. Finally, to assess the specificity of baclofen and GS39783 action, rats were slightly food-deprived and trained to lever-respond for food pellets. Results The rank of order of the reinforcing and motivational properties of alcohol was: P>sP>AA rats. Under both FR and PR schedules of reinforcement, the rank of order of potency and efficacy of baclofen and GS39783 in suppressing alcohol self-administration was: P>sP>AA rats. Only the highest dose of baclofen reduced lever-responding for food pellets; this effect was common to all three rat lines. Conversely, no dose of GS39783 altered lever-responding for food in any rat line. Conclusions These results suggest that: (a) the strength of the reinforcing and motivational properties of alcohol differ among P, sP, and AA rats; (b) the reinforcing and motivational properties of alcohol in P, sP, and AA rats are differentially sensitive to treatment with baclofen and GS39783; (c) the heterogeneity in sensitivity to baclofen and GS39783 of alcohol self-administration in P, sP, and AA rats may resemble the differential effectiveness of pharmacotherapies among the different typologies of human alcoholics; (d) the GABAB receptor is part of the neural substrate mediating the reinforcing and motivational properties of alcohol. PMID:22486245

Cajanus cajan Linn. (Leguminosae) prevents alcohol-induced rat liver damage and augments cytoprotective function.

PubMed

Kundu, Rakesh; Dasgupta, Suman; Biswas, Anindita; Bhattacharya, Anirban; Pal, Bikas C; Bandyopadhyay, Debashis; Bhattacharya, Shelley; Bhattacharya, Samir

2008-08-13

Cajanus cajan Linn. (Leguminosae) is a nontoxic edible herb, widely used in Indian folk medicine for the prevention of various liver disorders. In the present study we have demonstrated that methanol-aqueous fraction (MAF2) of Cajanus cajan leaf extract could prevent the chronically treated alcohol induced rat liver damage. Chronic doses of alcohol (3.7 g/ kg) orally administered to rats for 28 days and liver function marker enzymes such as GPT, GOT, ALP and anti-oxidant enzyme activities were determined. Effect of MAF2 at a dose of 50mg/kg body weight on alcohol treated rats was noted. Alcohol effected significant increase in liver marker enzyme activities and reduced the activities of anti-oxidant enzymes. Co-administration of MAF2 reversed the liver damage due to alcohol; it decreased the activities of liver marker enzymes and augmented antioxidant enzyme activities. We also demonstrate significant decrease of the phase II detoxifying enzyme, UDP-glucuronosyl transferase (UGT) activity along with a three- and two-fold decrease of UGT2B gene and protein expression respectively. MAF2 co-administration normalized UGT activity and revived the expression of UGT2B with a concomitant expression and nuclear translocation of Nrf2, a transcription factor that regulates the expression of many cytoprotective genes. Cajanus cajan extract therefore shows a promise in therapeutic use in alcohol induced liver dysfunction.

Drinking status but not acute alcohol consumption influences delay discounting.

PubMed

Adams, Sally; Attwood, Angela S; Munafò, Marcus R

2017-09-01

The aim of this study was to investigate the following: (a) the effects of acute alcohol on delay discounting; (b) the effects of drinking status on delayed discounting; and (c) whether these effects differ according to reward type (alcohol vs. money). Heavy and light social alcohol users (n = 96) were randomized to receive either an acute dose of alcohol at 0.4 or 0.6 g/kg or placebo in a between-subjects, double-blind design. Delay discounting of alcohol and monetary rewards was measured using a hyperbolic model, with higher scores indicative of greater delay discounting. ANOVA of discount scores indicated a main effect of reward type, where all participants had higher discount scores for alcohol versus money rewards. A main effect of drinking status was also observed, where heavier drinkers had higher discount scores compared with lighter drinkers. We did not observe a main effect of acute alcohol use on delay discounting or the hypothesized interactions between acute alcohol use and drinking status with reward type. Our data suggest that heavier drinkers discount the value of delayed rewards more steeply than lighter drinkers. Delay discounting may therefore be a promising marker of heavy alcohol consumption in social drinkers. Copyright © 2017 John Wiley & Sons, Ltd.

Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice

PubMed Central

Zhang, Yu-Jie; Xu, Dong-Ping; Wang, Fang; Zhou, Yue; Zheng, Jie; Li, Ya; Zhang, Jiao-Jiao

2017-01-01

Chronic excessive alcohol consumption (more than 40–80 g/day for males and more than 20–40 g/day for females) could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG) contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT), aspartate transaminase (AST), hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity. PMID:28567423

Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice.

PubMed

Zhou, Tong; Zhang, Yu-Jie; Xu, Dong-Ping; Wang, Fang; Zhou, Yue; Zheng, Jie; Li, Ya; Zhang, Jiao-Jiao; Li, Hua-Bin

2017-01-01

Chronic excessive alcohol consumption (more than 40-80 g/day for males and more than 20-40 g/day for females) could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG) contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT), aspartate transaminase (AST), hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity.

Behavioral effects of the combined use of alcohol and energy drinks on alcohol hangover in an experimental mice model.

PubMed

Asorey, Lucas G; Carbone, Silvia; Gonzalez, Bárbara J; Cutrera, Rodolfo A

2018-03-23

In last few years it has been a significant increase in the consumption of alcohol combined with energy drink. The aim of this work was to study the effect of this mixture in motor and affective behaviors during an alcohol hangover episode. Male Swiss mice received one of the following treatments: saline + sucrose; saline + energy drink; ethanol + sucrose; ethanol + energy drink. Ethanol dose was 3.8 g/kg BW (i.p.) and energy drink dose was 18 ml/kg BW (gavage) at ZT1 (8 am) (ZT: Zeitgeber time; ZT0: 7 am; lights on). The behavioral tests used were tight rope test to determine motor coordination; hanging wire test to study muscular strength; elevated plus maze and open field tests to evaluate anxiety like-behavior and locomotor activity. Tests were carried out at basal point that matched with lights onset and every 6 h up to 18 h after treatments. Hangover onset was established at ZT7 when blood alcohol concentration (BAC) was almost zero. Our results showed that the mixture of alcohol and energy drink altered significantly motor skills. Specifically, a significant decrease was observed in the performance of the animals in the tightrope and hanging wire tests in groups treated with the mixture of alcohol and energy drink. A significant impairment in the anxiety-like behavior was observed mainly at the beginning of alcohol hangover. These findings suggest that energy drink added to alcohol extends motor disabilities observed during an alcohol hangover episode in comparison with animals that received alcohol alone. Copyright © 2018 Elsevier B.V. All rights reserved.

Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner

PubMed Central

Cannady, Reginald; Fisher, Kristen R.; Graham, Caitlin; Crayle, Jesse; Besheer, Joyce; Hodge, Clyde W.

2015-01-01

Growing evidence indicates that drugs of abuse gain control over the individual by usurping glutamate-linked mechanisms of neuroplasticity in reward-related brain regions. Accordingly, we have shown that glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity in the amygdala is required for the positive reinforcing effects of alcohol, which underlie the initial stages of addiction. It is unknown, however, if enhanced AMPAR activity in the amygdala facilitates alcohol self-administration, which is a kernel premise of glutamate hypotheses of addiction. Here we show that low-dose alcohol (0.6 g/kg/30-min) self-administration increases phosphorylation (activation) of AMPAR subtype GluA1 S831 (pGluA1 S831) in the central amygdala (CeA), basolateral amygdala, and nucleus accumbens core (AcbC) of selectively bred alcohol-preferring P-rats as compared to behavior-matched (non-drug) sucrose controls. The functional role of enhanced AMPAR activity was assessed via site-specific infusion of the AMPAR positive modulator, aniracetam, in the CeA and AcbC prior to alcohol self-administration. Intra-CeA aniracetam increased alcohol- but not sucrose-reinforced responding, and was ineffective following intra-AcbC infusion. Since GluA1 S831 is a Ca2+/calmodulin-dependent protein kinase II (CaMKII) substrate, we sought to determine if AMPAR regulation of enhanced alcohol self-administration is dependent on CaMKII activity. Intra-CeA infusion of the cell-permeable CaMKII peptide inhibitor m-AIP dose-dependently reduced alcohol self-administration. A sub-threshold dose of m-AIP also blocked the aniracetam-induced escalation of alcohol self-administration, demonstrating that AMPAR-mediated potentiation of alcohol reinforcement requires CaMKII activity in the amygdala. Enhanced activity of plasticity-linked AMPAR-CaMKII signaling in the amygdala may promote escalated alcohol use via increased positive reinforcement during the initial stages of addiction. PMID:26742808

Drinking and driving behavior at stop signs and red lights.

PubMed

Wan, Jingyan; Wu, Changxu; Zhang, Yiqi; Houston, Rebecca J; Chen, Chang Wen; Chanawangsa, Panya

2017-07-01

Alcohol is one of the principal risk factors for motor vehicle crashes. One factor that contributes to vehicle crashes is noncompliance with stop signs and red lights. The present experiment investigated the effects of alcohol and drinking patterns on driving behavior at stop signs and red lights. 28 participants participated in drinking and simulated driving sessions during which they received a moderate dose of alcohol (0.08% BAC) or a placebo. Simulated driving tasks measured participants' driving performance at stop signs and red lights in response to each dose. Results suggested that alcohol impaired the driver control of speed and direction and prolonged their simple and complex reaction time, which were exhibited by impaired speed and lateral control, longer reaction time when the lights turned yellow, and lower deceleration towards stop signs and red lights. Visual degradation may also occur under alcohol intake. It was also suggested that alcohol impaired non-binge drinkers more severely. To be specific, higher acceleration was observed in impaired non-binge drinkers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alcohol consumption in late adolescence is associated with an increased risk of severe liver disease later in life.

PubMed

Hagström, Hannes; Hemmingsson, Tomas; Discacciati, Andrea; Andreasson, Anna

2018-03-01

High alcohol consumption is associated with an increased risk of severe liver disease. Current recommendations suggest it is safe for men to consume 30 grams of alcohol per day. We investigated the association between alcohol consumption early in life and later development of severe liver disease. We used data on alcohol consumption at conscription to military service from 43,296 men (18-20 years) in Sweden between 1969 and 1970. Outcomes were defined as incident diagnoses of severe liver disease from systematic national registration of clinical events until the end of 2009. A Cox regression model adjusted for body mass index, smoking, use of narcotics, cognitive ability and cardiovascular capacity was applied. During a mean follow-up of 37.8 years, 383 men developed severe liver disease. Alcohol consumption was associated with an increased risk of development of severe liver disease in a dose-response pattern (adjusted hazard ratio for every one gram/day increase 1.02; 95% CI 1.01-1.02). No evidence of a threshold effect was found. Importantly, a clear trend pointed towards an increased risk of severe liver disease in men who consumed less than 30 grams of alcohol per day. Alcohol consumption in young men is associated with an increased risk of severe liver disease, up to 39 years later in life. The risk was dose-dependent, with no sign of a threshold effect. Current guidelines for safe alcohol intake in men might have to be revised. We investigated more than 43,000 Swedish men in their late teens enlisted for conscription in 1969-1970. After almost 40 years of follow-up, we found that alcohol consumption was a significant risk factor for developing severe liver disease, independent of confounders. This risk was dose-dependent, and was most pronounced in men consuming two drinks per day or more. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Effect on gastric function and symptoms of drinking wine, black tea, or schnapps with a Swiss cheese fondue: randomised controlled crossover trial

PubMed Central

Heinrich, Henriette; Goetze, Oliver; Menne, Dieter; Iten, Peter X; Fruehauf, Heiko; Vavricka, Stephan R; Schwizer, Werner; Fried, Michael

2010-01-01

Objective To compare the effects of drinking white wine or black tea with Swiss cheese fondue followed by a shot of cherry schnapps on gastric emptying, appetite, and abdominal symptoms. Design Randomised controlled crossover study. Participants 20 healthy adults (14 men) aged 23-58. Interventions Cheese fondue (3260 kJ, 32% fat) labelled with 150 mg sodium 13Carbon-octanoate was consumed with 300 ml of white wine (13%, 40 g alcohol) or black tea in randomised order, followed by 20 ml schnapps (40%, 8 g alcohol) or water in randomised order. Main outcome measures Cumulative percentage dose of 13C substrate recovered over four hours (higher values indicate faster gastric emptying) and appetite and dyspeptic symptoms (visual analogue scales). Results Gastric emptying was significantly faster when fondue was consumed with tea or water than with wine or schnapps (cumulative percentage dose of 13C recovered 18.1%, 95% confidence interval 15.2% to 20.9% v 7.4%, 4.6% to 10.3%; P<0.001). An inverse dose-response relation between alcohol intake and gastric emptying was evident. Appetite was similar with consumption of wine or tea (difference 0.11, −0.12 to 0.34; P=0.35), but reduced if both wine and schnapps were consumed (difference −0.40, −0.01 to −0.79; P<0.046). No difference in dyspeptic symptoms was present. Conclusions Gastric emptying after a Swiss cheese fondue is noticeably slower and appetite suppressed if consumed with higher doses of alcohol. This effect was not associated with dyspeptic symptoms. Trial registration ClinicalTrials.gov NCT00943696. PMID:21156747

A Critical Review of the Effects of Nicotine and Alcohol Coadministration in Human Laboratory Studies.

PubMed

Dermody, Sarah S; Hendershot, Christian S

2017-03-01

Simultaneous use of cigarettes and alcohol is common and may be driven by nicotine increasing alcohol self-administration or vice versa. To better evaluate the causal nature of this relationship, we systematically reviewed human experimental laboratory studies that coadministered nicotine and alcohol with control conditions. Searches of PubMed/MEDLINE and PsycINFO databases and study bibliographies identified 30 studies that met our inclusion criteria. Research methodologies were critically reviewed. Effects of coadministration on drug self-administration and related factors such as craving, subjective response, motivation, and heart rate are reported. Results most strongly supported that alcohol increases nicotine and cigarette self-administration, whereas, depending on the context, nicotine increased, decreased, or had no effect on alcohol self-administration. Craving and subjective drug effects were also impacted by coadministration. Interaction effects of nicotine and alcohol on self-administration and subjective responses were reported infrequently. The effects may be moderated by a number of factors, including dose of administered drug and sex. Recommendations are made for future research, and clinical and policy implications of findings are discussed. Copyright © 2017 by the Research Society on Alcoholism.

Faster self-paced rate of drinking for alcohol mixed with energy drinks versus alcohol alone.

PubMed

Marczinski, Cecile A; Fillmore, Mark T; Maloney, Sarah F; Stamates, Amy L

2017-03-01

The consumption of alcohol mixed with energy drinks (AmED) has been associated with higher rates of binge drinking and impaired driving when compared with alcohol alone. However, it remains unclear why the risks of use of AmED are heightened compared with alcohol alone even when the doses of alcohol consumed are similar. Therefore, the purpose of this laboratory study was to investigate if the rate of self-paced beverage consumption was faster for a dose of AmED versus alcohol alone using a double-blind, within-subjects, placebo-controlled study design. Participants (n = 16) of equal gender who were social drinkers attended 4 separate test sessions that involved consumption of alcohol (1.97 ml/kg vodka) and energy drinks, alone and in combination. On each test day, the dose assigned was divided into 10 cups. Participants were informed that they would have a 2-h period to consume the 10 drinks. After the self-paced drinking period, participants completed a cued go/no-go reaction time (RT) task and subjective ratings of stimulation and sedation. The results indicated that participants consumed the AmED dose significantly faster (by ∼16 min) than the alcohol dose. For the performance task, participants' mean RTs were slower in the alcohol conditions and faster in the energy-drink conditions. In conclusion, alcohol consumers should be made aware that rapid drinking might occur for AmED beverages, thus heightening alcohol-related safety risks. The fast rate of drinking may be related to the generalized speeding of responses after energy-drink consumption. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Effect of Piper betle leaf extract on alcoholic toxicity in the rat brain.

PubMed

Saravanan, R; Rajendra Prasad, N; Pugalendi, K V

2003-01-01

The protective effect of Piper betle, a commonly used masticatory, has been examined in the brain of ethanol-administered Wistar rats. Brain of ethanol-treated rats exhibited increased levels of lipids, lipid peroxidation, and disturbances in antioxidant defense. Subsequent to the experimental induction of toxicity (i.e., the initial period of 30 days), aqueous P. betle extract was simultaneously administered in three different doses (100, 200, and 300 mg kg(-1)) for 30 days along with the daily dose of alcohol. P. betle coadministration resulted in significant reduction of lipid levels (free fatty acids, cholesterol, and phospholipids) and lipid peroxidation markers such as thiobarbituric acid reactive substances and hydroperoxides. Further, antioxidants, like reduced glutathione, vitamin C, vitamin E, superoxide dismutase, catalase, and glutathione peroxidase, were increased in P. betle-coadministered rats. The higher dose of extract (300 mg kg(-1)) was more effective, and these results indicate the neuroprotective effect of P. betle in ethanol-treated rats.

Acute comparison of clovoxamine and mianserin, alone and in combination with ethanol, on human psychomotor performance.

PubMed

Strömberg, C; Mattila, M J

1987-05-01

Objective and subjective effects on human performance of clovoxamine and mianserin were measured in 12 student volunteers who participated in 12 test sessions and received single doses of clovoxamine 50 mg, 100 mg and 150 mg, mianserin 20 mg, and placebo in a double-blind and cross-over manner. Each test drug was given twice, both in combination with alcohol 0.8 g/kg and with a non-alcoholic drink. The tests included tracking, body balance, flicker fusion, horizontal nystagmus, digit symbol substitution, recall memory, and subjective assessments on visual analogue scales. Mianserin and alcohol impaired objective performance in most tests, and their combination showed at least an additive effect. Alcohol counteracted rather than increased mianserin-induced subjective sedation. Clovoxamine neither differed significantly from placebo nor increased alcohol effects. On the contrary, clovoxamine 150 mg reduced significantly alcohol-induced body sway. No evidence of pharmacokinetic interactions were found between the study drugs and alcohol.

Neurotoxic Effects of Alcohol in Adolescence

PubMed Central

Jacobus, Joanna; Tapert, Susan F.

2013-01-01

This review examines neuroimaging and neurocognitive findings on alcohol-related toxicity in adolescents. Teens who meet criteria for alcohol use disorders, as well as those who engage in subdiagnostic binge drinking behaviors, often show poorer neurocognitive performance, alterations in gray and white matter brain structure, and discrepant functional brain activation patterns when compared to nonusing and demographically matched controls. Abnormalities are also observed in teens with a family history of alcoholism, and such differences in neuromaturation may leave youths at increased risk for the development of an alcohol use disorder or increased substance use severity. More prospective investigations are needed, and future work should focus on disentangling preexisting differences from dose-dependent effects of alcohol on neurodevelopment. Intervention strategies that utilize neuroimag-ing findings (e.g., identified weaknesses in particular neural substrates and behavioral correlates) may be helpful in both prevention and intervention campaigns for teens both pre- and postinitiation of alcohol use. PMID:23245341

The sensitivity of laboratory tests assessing driving related skills to dose-related impairment of alcohol: A literature review.

PubMed

Jongen, S; Vuurman, E F P M; Ramaekers, J G; Vermeeren, A

2016-04-01

Laboratory tests assessing driving related skills can be useful as initial screening tools to assess potential drug induced impairment as part of a standardized behavioural assessment. Unfortunately, consensus about which laboratory tests should be included to reliably assess drug induced impairment has not yet been reached. The aim of the present review was to evaluate the sensitivity of laboratory tests to the dose dependent effects of alcohol, as a benchmark, on performance parameters. In total, 179 experimental studies were included. Results show that a cued go/no-go task and a divided attention test with primary tracking and secondary visual search were consistently sensitive to the impairing effects at medium and high blood alcohol concentrations. Driving performance assessed in a simulator was less sensitive to the effects of alcohol as compared to naturalistic, on-the-road driving. In conclusion, replicating results of several potentially useful tests and their predictive validity of actual driving impairment should deserve further research. In addition, driving simulators should be validated and compared head to head to naturalistic driving in order to increase construct validity. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Alcohol’s Effects on the Cardiovascular System

PubMed Central

Piano, Mariann R.

2017-01-01

Alcohol use has complex effects on cardiovascular (CV) health. The associations between drinking and CV diseases such as hypertension, coronary heart disease, stroke, peripheral arterial disease, and cardiomyopathy have been studied extensively and are outlined in this review. Although many behavioral, genetic, and biologic variants influence the interconnection between alcohol use and CV disease, dose and pattern of alcohol consumption seem to modulate this most. Low-to-moderate alcohol use may mitigate certain mechanisms such as risk and hemostatic factors affecting atherosclerosis and inflammation, pathophysiologic processes integral to most CV disease. But any positive aspects of drinking must be weighed against serious physiological effects, including mitochondrial dysfunction and changes in circulation, inflammatory response, oxidative stress, and programmed cell death, as well as anatomical damage to the CV system, especially the heart itself. Both the negative and positive effects of alcohol use on particular CV conditions are presented here. The review concludes by suggesting several promising avenues for future research related to alcohol use and CV disease. These include using direct biomarkers of alcohol to confirm self-report of alcohol consumption levels; studying potential mediation of various genetic, socioeconomic, and racial and ethnic factors that may affect alcohol use and CV disease; reviewing alcohol–medication interactions in cardiac patients; and examining CV effects of alcohol use in young adults and in older adults. PMID:28988575

Alcohol affects video lottery terminal (VLT) gambling behaviors and cognitions differently.

PubMed

Ellery, Michael; Stewart, Sherry H

2014-03-01

People frequently combine alcohol use and gambling. However, our understanding of the effects of alcohol on gambling behavior is limited, both in terms of what the effects are and how they occur. The effects of a moderately intoxicating dose of alcohol (i.e., a blood alcohol concentration of .06 g%) on the video lottery terminal (VLT) gambling behaviors and cognitions of community-recruited nonpathological (n = 30) and probable pathological gamblers (n = 30) were compared. Alcohol increased the rate of double up betting (i.e., choosing to play a bonus game, after a winning video poker hand, which involves trying to pick a higher ranked card than the dealer's card from among 5 face down cards) of probable pathological gamblers, but did not influence their irrational beliefs about VLT play. Alcohol maintained the irrational beliefs about VLT play of nonpathological gamblers, but did not influence their gambling behaviors. Results are consistent with a growing body of research finding that gambling cognitions have an equivocal role in explaining actual gambling behaviors. Potential mechanisms for the observed effects are discussed. Applied implications discussed include: educating regular VLT players about the effects of alcohol on irrational gambling cognitions; reconsidering policies and practices that make alcohol available where machine gambling takes place; and targeting even moderate alcohol use in the treatment of gambling problems.

Dutch courage? Effects of acute alcohol consumption on self-ratings and observer ratings of foreign language skills.

PubMed

Renner, Fritz; Kersbergen, Inge; Field, Matt; Werthmann, Jessica

2018-01-01

A popular belief is that alcohol improves the ability to speak in a foreign language. The effect of acute alcohol consumption on perceived foreign language performance and actual foreign language performance in foreign language learners has not been investigated. The aim of the current study was to test the effects of acute alcohol consumption on self-rated and observer-rated verbal foreign language performance in participants who have recently learned this language. Fifty native German speakers who had recently learned Dutch were randomized to receive either a low dose of alcohol or a control beverage that contained no alcohol. Following the experimental manipulation, participants took part in a standardized discussion in Dutch with a blinded experimenter. The discussion was audio-recorded and foreign language skills were subsequently rated by two native Dutch speakers who were blind to the experimental condition (observer-rating). Participants also rated their own individual Dutch language skills during the discussion (self-rating). Participants who consumed alcohol had significantly better observer-ratings for their Dutch language, specifically better pronunciation, compared with those who did not consume alcohol. However, alcohol had no effect on self-ratings of Dutch language skills. Acute alcohol consumption may have beneficial effects on the pronunciation of a foreign language in people who have recently learned that language.

Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers.

PubMed

Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

2011-03-01

The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose-response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug-response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

14-Methoxymetopon, a highly potent mu opioid agonist, biphasically affects ethanol intake in Sardinian alcohol-preferring rats.

PubMed

Sabino, Valentina; Cottone, Pietro; Steardo, Luca; Schmidhammer, Helmut; Zorrilla, Eric P

2007-07-01

Increased opioidergic activity is thought to increase the propensity to consume ethanol. However, the dose monotonicity and receptor subtype for this effect remain uncertain. 14-methoxymetopon is a centrally acting, selective micro opioid receptor agonist with greater systemic antinociceptive potency than morphine and a putatively improved therapeutic index. To determine whether 14-methoxymetopon influenced voluntary ethanol intake in Sardinian alcohol-preferring (sP) rats. Male sP rats with continuous 2-bottle choice access to ethanol (10% v/v) or water were subjects. The effects of systemic 14-methoxymetopon administration (2, 5, 12.25, 30 micro/kg, s.c.) on 4-h ethanol intake were determined. The ability of naltrexone (50 micro/kg, s.c.), an opioid antagonist, to block actions of 14-methoxymetopon (12.25, 30 micro/kg, s.c.) was examined as were the effects of 14-methoxymetopon (12.25 micro/kg, s.c.) on self-administered blood alcohol levels (BALs) and clearance of a passive ethanol bolus (1 g/kg). Finally, the effects of central 14-methoxymetopon administration (0.0003-100 ng, i.c.v.) on 4-h ethanol intake were evaluated. Systemic 14-methoxymetopon very potently and dose-dependently suppressed ethanol and food intake for 30 min, followed by a greater, longer-lasting, and behaviorally specific increase in ethanol intake. The increased ethanol intake led to threefold higher BALs, was naltrexone-reversible, and not due to altered ethanol clearance. Intracerebroventricular 14-methoxymetopon administration rapidly altered ethanol intake per an inverted U-shaped dose-response function, increasing it at a 10 pg dose, while suppressing it at a 10,000-fold higher dose. The novel mu analgesic increases ethanol intake, a potential therapeutic liability, and results suggest a non-monotonic influence of brain mu opioid receptor stimulation on ethanol intake.

Alcohol and bone: review of dose effects and mechanisms.

PubMed

Maurel, D B; Boisseau, N; Benhamou, C L; Jaffre, C

2012-01-01

Alcohol is widely consumed across the world. It is consumed in both social and cultural settings. Until recently, two types of alcohol consumption were recognized: heavy chronic alcohol consumption or light consumption. Today, there is a new pattern of consumption among teenagers and young adults namely: binge drinking. Heavy alcohol consumption is detrimental to many organs and tissues, including bones, and is known to induce secondary osteoporosis. Some studies, however, have reported benefits from light alcohol consumption on bone parameters. To date, little is known regarding the effects of binge drinking on bone health. Here, we review the effects of three different means of alcohol consumption: light, heavy, and binge drinking. We also review the detailed literature on the different mechanisms by which alcohol intake may decrease bone mass and strength. The effects of alcohol on bone are thought to be both direct and indirect. The decrease in bone mass and strength following alcohol consumption is mainly due to a bone remodeling imbalance, with a predominant decrease in bone formation. Recent studies, however, have reported new mechanisms by which alcohol may act on bone remodeling, including osteocyte apoptosis, oxidative stress, and Wnt signalling pathway modulation. The roles of reduced total fat mass, increased lipid content in bone marrow, and a hypoleptinemia are also discussed.

Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma oxytocin levels.

PubMed

Bershad, Anya K; Kirkpatrick, Matthew G; Seiden, Jacob A; de Wit, Harriet

2015-06-01

Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), seems to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system has been implicated in responses to several other drugs of abuse. Here, we sought to investigate the effects of 2 other "social" drugs on plasma oxytocin levels--methamphetamine and alcohol. Based on their shared capacity to enhance sociability, we hypothesized that both methamphetamine and alcohol would increase plasma oxytocin levels. In study 1, 11 healthy adult volunteers attended 3 sessions during which they received methamphetamine (10 mg or 20 mg) or placebo under double-blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin levels were measured at regular intervals throughout the sessions. In study 2, 8 healthy adult volunteers attended a single session during which they received 1 beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin levels were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither of these drugs increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified.

Subchronic toxicity studies of t-butyl alcohol in rats and mice.

PubMed

Lindamood, C; Farnell, D R; Giles, H D; Prejean, J D; Collins, J J; Takahashi, K; Maronpot, R R

1992-07-01

The purpose of this study was to evaluate the toxicity of t-butyl alcohol, an important commodity chemical, an additive to unleaded gasoline, and a contaminant of drinking water. Ninety-day toxicity studies were conducted in B6C3F1 mice and Fischer 344 (F344) rats of both sexes using dosed water. Dose levels of t-butyl alcohol were 0, 0.25, 0.5, 1, 2, and 4% (w/v). Lethality was observed at the 4% level of both sexes and species. Weight-gain depression was present in all dose levels of male rats; 4% female rats; 1, 2, and 4% male mice; and 2 and 4% female mice. Water consumption was increased at lower dose levels in male rats and decreased in the higher dose levels of both sexes of rats and female mice. Clinical signs in rats were ataxia in both sexes and hypoactivity in males. Clinical signs in mice were ataxia, abnormal posture, and hypoactivity. In rats, urine volumes were reduced, in association with crystalluria. Gross lesions at necropsy were urinary tract calculi, renal pelvic and ureteral dilatation, and thickening of the urinary bladder mucosa. Microscopic lesions were hyperplasia of transitional epithelia and inflammation of the urinary bladder. In male rats treated with t-butyl alcohol, microscopic renal changes were suggestive of alpha-2 mu-globulin nephropathy. No-effect levels for the urinary tract lesions were 1% in male rats and mice (803.7 mg/kg/day for the male rats and 1565.8 mg/kg/day for the male mice) and 2% in female rats and mice (1451.5 mg/kg/day for the female rats and 4362.9 mg/kg/day for the female mice). The results indicate that in rodents the urinary tract is the target organ for t-butyl alcohol toxicity, and males are more sensitive to t-butyl alcohol toxicity than females.

The Alcohol Sensitivity Questionnaire: Evidence for Construct Validity

PubMed Central

Fleming, Kimberly A.; Bartholow, Bruce D.; Hilgard, Joseph B.; McCarthy, Denis M.; O’Neill, Susan E.; Steinley, Douglas; Sher, Kenneth J.

2016-01-01

Background Variability in sensitivity to the acute effects of alcohol is an important risk factor for the development of alcohol use disorder (AUD). The most commonly used retrospective self-report measure of sensitivity, the Self-Rating of the Effects of Alcohol form (SRE), queries a limited number of alcohol effects and relies on respondents’ ability to recall experiences that might have occurred in the distant past. Here, we investigated the construct validity of an alternative measure that queries a larger number of alcohol effects, the Alcohol Sensitivity Questionnaire (ASQ), and compared it to the SRE in predicting momentary subjective responses to an acute dose of alcohol. Method Healthy young adults (N = 423) completed the SRE and the ASQ and then were randomly assigned to consume either alcohol or a placebo beverage (between-subjects manipulation). Stimulation and sedation (Biphasic Alcohol Effects Scale) and subjective intoxication were measured multiple times after drinking. Results Hierarchical linear models showed that the ASQ reliably predicted each of these outcomes following alcohol but not placebo consumption, provided unique prediction beyond that associated with differences in recent alcohol involvement, and was preferred over the SRE (in terms of model fit) in direct model comparisons of stimulation and sedation. Conclusions The ASQ compared favorably with the better-known SRE in predicting increased stimulation and reduced sedation following an acute alcohol challenge. The ASQ appears to be a valid self-report measure of alcohol sensitivity and therefore holds promise for identifying individuals at-risk for AUD and related problems. PMID:27012527

Evaluation of effect of minocycline on rewarding potential and alcohol relapse in place preference model in mice.

PubMed

Gajbhiye, Snehalata V; Tripathi, Raakhi K; Salve, Bharat; Petare, Anup; Potey, Anirudha V

2017-05-10

Medical management for alcohol abuse has limitations. Alcohol consumption activates N-methyl-d-aspartate receptors and release of nitric oxide which can be inhibited by minocycline as it readily crosses blood brain barrier and may have effect on alcohol consumption. Thus, study objective is to evaluate the effect of minocycline on rewarding property, extinction and the reinstatement phenomenon induced by alcohol in a model of conditioned place preference (CPP) in mice. To evaluate rewarding effects of alcohol, CPP procedure consisted of 4 parts, including adaptation (day 1), pre-conditioning test (day 2), conditionings with alcohol (days 3, 5, 7 and 9) or saline (days 4, 6, 8 and 10) and postconditioning test (day 11) conducted on 11 consecutive days. The groups included were saline treated group (alcohol control), naltrexone - 1mg/kg (positive control), and minocycline in the doses of 10, 30 and 50mg/kg. To evaluate the effect of minocycline on alcohol relapse, CPP procedure consisted 6 parts, the first 4 were the same as enumerated above followed by extinction (days 12-16) and reinstatement phase (day 17). The time spent in alcohol paired compartment by different groups, revealed that minocycline and naltrexone significantly attenuated alcohol-induced place preference compared to alcohol control (p<0.05). Pretreatment with minocycline and naltrexone blocked reinstatement of extinguished CPP. Minocycline may have a role in attenuating the rewarding property of alcohol and prevent alcohol relapse. Copyright © 2017 Elsevier B.V. All rights reserved.

Attempted Training of Alcohol Approach and Drinking Identity Associations in US Undergraduate Drinkers: Null Results from Two Studies

PubMed Central

Lindgren, Kristen P.; Wiers, Reinout W.; Teachman, Bethany A.; Gasser, Melissa L.; Westgate, Erin C.; Cousijn, Janna; Enkema, Matthew C.; Neighbors, Clayton

2015-01-01

There is preliminary evidence that approach avoid training can shift implicit alcohol associations and improve treatment outcomes. We sought to replicate and extend those findings in US undergraduate social drinkers (Study 1) and at-risk drinkers (Study 2). Three adaptations of the approach avoid task (AAT) were tested. The first adaptation – the approach avoid training – was a replication and targeted implicit alcohol approach associations. The remaining two adaptations – the general identity and personalized identity trainings – targeted implicit drinking identity associations, which are robust predictors of hazardous drinking in US undergraduates. Study 1 included 300 undergraduate social drinkers. They were randomly assigned to real or sham training conditions for one of the three training adaptations, and completed two training sessions, spaced one week apart. Study 2 included 288 undergraduates at risk for alcohol use disorders. The same training procedures were used, but the two training sessions occurred within a single week. Results were not as expected. Across both studies, the approach avoid training yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes. The general identity training also yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes with one exception; individuals who completed real training demonstrated no changes in drinking refusal self-efficacy whereas individuals who completed sham training had reductions in self-efficacy. Finally, across both studies, the personalized identity training yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes. Despite having relatively large samples and using a well-validated training task, study results indicated all three training adaptations were ineffective at this dose in US undergraduates. These findings are important because training studies are costly and labor-intensive. Future research may benefit from focusing on more severe populations, pairing training with other interventions, increasing training dose, and increasing gamification of training tasks. PMID:26241316

Opiate-induced dopamine release is modulated by severity of alcohol dependence: an [(18)F]fallypride positron emission tomography study.

PubMed

Spreckelmeyer, Katja N; Paulzen, Michael; Raptis, Mardjan; Baltus, Thomas; Schaffrath, Sabrina; Van Waesberghe, Julia; Zalewski, Magdalena M; Rösch, Frank; Vernaleken, Ingo; Schäfer, Wolfgang M; Gründer, Gerhard

2011-10-15

Preclinical data implicate the reinforcing effects of alcohol to be mediated by interaction between the opioid and dopamine systems of the brain. Specifically, alcohol-induced release of β-endorphins stimulates μ-opioid receptors (MORs), which is believed to cause dopamine release in the brain reward system. Individual differences in opioid or dopamine neurotransmission have been suggested to be responsible for enhanced liability to abuse alcohol. In the present study, a single dose of the MOR agonist remifentanil was administered in detoxified alcohol-dependent patients and healthy control subjects to mimic the β-endorphin-releasing properties of ethanol and to assess the effects of direct MOR stimulation on dopamine release in the mesolimbic reward system. Availability of D(2/3) receptors was assessed before and after single-dose administration of the MOR agonist remifentanil in 11 detoxified alcohol-dependent patients and 11 healthy control subjects with positron emission tomography with the radiotracer [(18)F]fallypride. Severity of dependence as assessed with the Alcohol Use Disorders Identification Test was compared with remifentanil-induced percentage change in [(18)F]fallypride binding (Δ%BP(ND)). The [(18)F]fallypride binding potentials (BP(ND)s) were significantly reduced in the ventral striatum, dorsal putamen, and amygdala after remifentanil application in both patients and control subjects. In the patient group, ventral striatum Δ%BP(ND) was correlated with the Alcohol Use Disorders Identification Test score. The data provide evidence for a MOR-mediated interaction between the opioid and the dopamine system, supporting the assumption that one way by which alcohol unfolds its rewarding effects is via a MOR-(γ-aminobutyric acid)-dopamine pathway. No difference in dopamine release was found between patients and control subjects, but evidence for a patient-specific association between sensitivity to MOR stimulation and severity of alcohol dependence was found. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents.

PubMed

McBride, W J; Li, T K

1998-01-01

This review discusses efforts to develop rodent models for the study of neurobiological mechanisms underlying chronic alcohol drinking, alcoholism, and abnormal alcohol-seeking behavior. Selective breeding has produced stable lines of rats that reliably exhibit high and (for comparison purposes) low voluntary alcohol consumption. In addition, animal models of chronic ethanol self-administration have been developed in rodents, who do not have a genetic predisposition for high alcohol-seeking behavior, to explore environmental influences in ethanol drinking and the effects of physical dependence on alcohol self-administration. The selectively bred high-preference animals reliably self-administer ethanol by free-choice drinking and operantly respond for oral ethanol in amounts that produce pharmacologically meaningful blood alcohol concentrations (50 to 200 mg% and higher). In addition, the alcohol-preferring rats will self-administer ethanol by intragastric infusion. With chronic free-choice drinking, the high alcohol-preferring rats develop tolerance to the high-dose effects of ethanol and show signs of physical dependence after the withdrawal of alcohol. Compared with nonpreferring animals, the alcohol-preferring rats are less sensitive to the sedative-hypnotic effects of ethanol and develop tolerance more quickly to high-dose ethanol. Nonselected common stock rats can be trained to chronically self-administer ethanol following its initial presentation in a palatable sucrose or saccharin solution, and the gradual replacement of the sucrose or saccharin with ethanol (the sucrose/saccharin-fade technique). Moreover, rats that are trained in this manner and then made dependent by ethanol-vapor inhalation or liquid diet increase their ethanol self-administration during the withdrawal period. Both the selectively bred rats and common-stock rats demonstrate "relapse" and an alcohol deprivation effect following 2 or more weeks of abstinence. Systemic administration of agents that (1) increase synaptic levels of serotonin (5-HT) or dopamine (DA); (2) activate 5-HT1A, 5-HT2, D2, D3, or GABA(A) receptors; or (3) block opioid and 5-HT3 receptors decrease ethanol intake in most animal models. Neurochemical, neuroanatomical, and neuropharmacological studies indicate innate differences exist between the high alcohol-consuming and low alcohol-consuming rodents in various CNS limbic structures. In addition, reduced mesolimbic DA and 5-HT function have been observed during alcohol withdrawal in common stock rats. Depending on the animal model under study, abnormalities in the mesolimbic dopamine pathway, and/or the serotonin, opioid, and GABA systems that regulate this pathway may underlie vulnerability to the abnormal alcohol-seeking behavior in the genetic animal models.

A Preliminary Investigation of the Effect of Acute Alcohol on Dopamine Transmission as Assessed by [11 C]-(+)-PHNO.

PubMed

Thiruchselvam, Thulasi; Wilson, Alan A; Boileau, Isabelle; Le Foll, Bernard

2017-06-01

Previous positron emission tomography (PET) studies exploring the effect of acute alcohol on dopamine (DA) levels have yielded inconsistent results, with only some studies suggesting increased synaptic DA levels after an alcohol challenge. The D 2 /D 3 agonist radiotracer, [ 11 C]-(+)-propyl-hexahydro-naphtho-oxazin ([ 11 C]-(+)-PHNO), has greater sensitivity to synaptic DA fluctuation than previously used antagonist radiotracers and is in principle more suitable for imaging alcohol-induced changes in DA. Its high affinity for the D 3 receptor also enables measuring changes in D 3 -rich brain areas which have previously been unexplored. The aim of this study was to investigate whether alcohol reduces [ 11 C]-(+)-PHNO binding in the striatum and in D 3 -rich extra-striatal areas. Eight healthy drinkers underwent 2 [ 11 C]-(+)-PHNO PET scans following alcohol and placebo in a randomized, single-blind, crossover design. [ 11 C]-(+)-PHNO binding in the striatum and in the extra-striatal regions were compared between the 2 scans. Acute alcohol administration did not significantly reduce [ 11 C]-(+)-PHNO binding in either the limbic striatum (d = 0.64), associative striatum (d < 0.20), or the sensorimotor striatum (d < 0.15). Similarly, there were no changes in binding in the D 3 -rich areas of the ventral pallidum (d = 0.53), substantia nigra (d < 0.15), or globus pallidus (d < 0.15). However, greater percent change in [ 11 C]-(+)-PHNO binding (ΔBP ND ) between scans was related to lower blood alcohol levels. Using the agonist radiotracer, [ 11 C]-(+)-PHNO, our preliminary findings suggest that alcohol is not associated with robust changes in tracer binding in striatal or extra-striatal regions. However, we found that changes in [ 11 C]-(+)-PHNO binding following alcohol are dependent on blood alcohol levels suggesting that increases in DA may occur at lower stimulating doses. The effect of lower doses of alcohol on DA warrants further investigation in a larger study. Copyright © 2017 by the Research Society on Alcoholism.

Differential effects of alcohol on working memory: distinguishing multiple processes.

PubMed

Saults, J Scott; Cowan, Nelson; Sher, Kenneth J; Moreno, Matthew V

2007-12-01

The authors assessed effects of alcohol consumption on different types of working memory (WM) tasks in an attempt to characterize the nature of alcohol effects on cognition. The WM tasks varied in 2 properties of materials to be retained in a 2-stimulus comparison procedure. Conditions included (a) spatial arrays of colors, (b) temporal sequences of colors, (c) spatial arrays of spoken digits, and (d) temporal sequences of spoken digits. Alcohol consumption impaired memory for auditory and visual sequences but not memory for simultaneous arrays of auditory or visual stimuli. These results suggest that processes needed to encode and maintain stimulus sequences, such as rehearsal, are more sensitive to alcohol intoxication than other WM mechanisms needed to maintain multiple concurrent items, such as focusing attention on them. These findings help to resolve disparate findings from prior research on alcohol's effect on WM and on divided attention. The results suggest that moderate doses of alcohol impair WM by affecting certain mnemonic strategies and executive processes rather than by shrinking the basic holding capacity of WM. (c) 2008 APA, all rights reserved.

The Desire to Drink Alcohol is Enhanced with High Caffeine Energy Drink Mixers

PubMed Central

Marczinski, Cecile A.; Fillmore, Mark T.; Stamates, Amy L.; Maloney, Sarah F.

2017-01-01

Background Consumption of alcohol mixed with energy drinks (AmED) has been associated with a variety of risks beyond that observed with alcohol alone. Consumers of AmED beverages are more likely to engage in heavy episodic (binge) drinking. The purpose of this study was to investigate whether the consumption of high caffeine energy drink mixers with alcohol would increase the desire to drink alcohol compared to the same amount of alcohol alone using a double-blind, within-subjects, placebo-controlled study design. Methods Participants (n = 26) of equal gender who were social drinkers attended 6 double-blind dose administration sessions that involved consumption of alcohol and energy drinks, alone and in combination. On each test day, participants received 1 of 6 possible doses: 1) 1.21 ml/kg vodka + 3.63 ml/kg decaffeinated soft drink, 2) 1.21 ml/kg vodka + 3.63 ml/kg energy drink, 3) 1.21 ml/kg vodka + 6.05 ml/kg energy drink, 4) 3.36 ml/kg decaffeinated soft drink, 5) 3.36 ml/kg energy drink, and 6) 6.05 ml/kg energy drink. Following dose administration, participants repeatedly completed self-reported ratings on the Desire for Drug questionnaire and provided breath alcohol readings. Results Alcohol alone increased the subjective ratings of “desire for more alcohol” compared to placebo doses. Energy drink mixers with the alcohol increased desire for more alcohol ratings beyond that observed with alcohol alone. Conclusions This study provides laboratory evidence that AmED beverages lead to greater desire to drink alcohol versus the same amount of alcohol consumed alone. The findings are consistent with results from animal studies indicating that caffeine increases the rewarding and reinforcing properties of alcohol. PMID:27419377

The nicotine + alcohol interoceptive drug state: contribution of the components and effects of varenicline in rats.

PubMed

Randall, Patrick A; Cannady, Reginald; Besheer, Joyce

2016-08-01

Nicotine and alcohol co-use is highly prevalent, and as such, individuals experience the interoceptive effects of both substances together. Therefore, examining sensitivity to a compound nicotine and alcohol (N + A) interoceptive cue is critical to broaden our understanding of mechanisms that may contribute to nicotine and alcohol co-use. This work assessed the ability of a N + A interoceptive cue to gain control over goal-tracking behavior and determined the effects of the α4β2 nicotinic partial agonist and smoking cessation compound varenicline on sensitivity to N + A. Two groups of male Long Evans rats were trained to discriminate N + A (0.4 mg/kg nicotine + 1 g/kg alcohol, intragastric gavage (IG)) from water under two different training conditions using a Pavlovian drug discrimination task. The effects of varenicline (0, 1, 3 mg/kg, intraperitoneally (IP)) administered alone and on sensitivity to N + A and the components were determined. Under both training conditions, N + A rapidly gained control over behavior, with a greater contribution of nicotine to the N + A compound cue. Varenicline fully substituted for the N + A training dose, and varenicline (1 mg/kg) enhanced sensitivity to the lowest N + A dose (0.1 N + 0.1 A). Given the high selectivity of varenicline for the α4β2 receptor, this finding suggests a functional role for α4β2 nicotinic acetylcholine receptors (nAChRs) in modulating sensitivity to N + A. The N + A compound cue is a unique cue that is modulated, in part, by activity at the α4β2 nAChR. These findings advance understanding of the interoceptive effects of nicotine and alcohol in combination and may have implications in relation to their co-use.

Binge drinking and anxiety at the end of the nocturnal period in alcohol-preferring sP rats.

PubMed

Colombo, Giancarlo; Lobina, Carla; Lorrai, Irene; Acciaro, Carla; Maccioni, Paola; Gessa, Gian Luigi

2017-09-01

Previous studies suggested that exposure of Sardinian alcohol-preferring (sP) rats to daily drinking sessions of 1 h, during the dark phase of the light/dark cycle, with multiple alcohol concentrations, and unpredictable access to alcohol, resulted in exceptionally high intakes of alcohol when the drinking session occurred over the last hours of the dark phase. Additionally, higher levels of anxiety-related behaviors were observed at the 12th, rather than 1st, hour of the dark phase, suggesting that uncertainty of time of alcohol access and expectation of alcohol availability produced an emotional "distress". The present study was designed to provide pharmacological support to the hypothesis that high alcohol intake under this drinking procedure is secondary to exacerbation of the anxiety-like state of sP rats. To this end, sP rats were initially exposed to daily 1-h drinking sessions during the dark phase and with multiple alcohol concentrations (0%, 10%, 20%, and 30%; v/v); time of alcohol exposure was changed each day and was unpredictable to rats. Rats were then treated acutely with non-sedative doses of diazepam (0, 1, 2, and 3 mg/kg; intraperitoneally [i.p.]) before two drinking sessions occurring at the 1st and 12th hour of the dark phase, respectively. Treatment with diazepam was ineffective at the 1st hour; conversely, it selectively reduced alcohol intake (up to 50% at the dose of 3 mg/kg) at the 12th hour. The preferential effectiveness of diazepam in reducing alcohol intake when the drinking session occurred at the 12th hour of the dark phase is consistent with the hypothesis that uncertainty of time of alcohol access and expectation of alcohol availability generated an emotional "distress" that rats counterbalanced with high alcohol drinking; the results of the present study are interpreted as the anxiolytic effects of diazepam substituting for those of alcohol, resulting in the observed reduction in alcohol intake. Copyright © 2017 Elsevier Inc. All rights reserved.

Do insulin-like growth factors mediate the effect of alcohol on breast cancer risk?

PubMed

Yu, H; Berkel, J

1999-06-01

Despite a large number of epidemiologic studies demonstrating an increased risk of breast cancer in association with alcohol consumption, a causal relationship between alcohol intake and breast cancer risk remains to be determined. Several biological mechanisms have been proposed, but none of them explains well the features of the association, i.e. a modest increase in risk, a limited range of dose-response relationship and no further increase in risk among heavy drinkers. A new mechanism underlying a possible biological role of alcohol in breast cancer is proposed in this paper. Moderate consumption of alcohol increases the production of insulin-like growth factors (IGFs) by the liver and elevated IGFs via circulation stimulate or promote the development and/or growth of breast cancer. The effect of alcohol on IGF production declines among heavy drinkers as alcohol-caused liver-function damage results in no further increase in IGF production. Therefore, compared to moderate drinkers, heavy alcohol users do not have a higher risk of breast cancer.

Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol-Preferring (P) Rats.

PubMed

Froehlich, Janice C; Nicholson, Emily R; Dilley, Julian E; Filosa, Nick J; Rademacher, Logan C; Smith, Teal N

2017-08-01

Most alcoholics experience periods of voluntary alcohol abstinence or imposed alcohol deprivation followed by a return to alcohol drinking. This study examined whether varenicline (VAR) reduces alcohol intake during a return to drinking after periods of alcohol deprivation in rats selectively bred for high alcohol drinking (the alcohol preferring or "P" rats). Alcohol-experienced P rats were given 24-hour access to food and water and scheduled access to alcohol (15% and 30% v/v) for 2 h/d. After 4 weeks, rats were deprived of alcohol for 2 weeks, followed by reaccess to alcohol for 2 weeks, and this pattern was repeated for a total of 3 cycles. Rats were fed either vehicle (VEH) or VAR, in doses of 0.5, 1.0, or 2.0 mg/kg BW, at 1 hour prior to onset of the daily alcohol reaccess period for the first 5 days of each of the 3 alcohol reaccess cycles. Low-dose VAR (0.5 mg/kg BW) reduced alcohol intake during the 5 days of drug treatment in alcohol reaccess cycles 1 and 2. Higher doses of VAR (1.0 mg/kg BW and 2.0 mg/kg BW) reduced alcohol intake during the 5 days of treatment in all 3 alcohol reaccess cycles. The decrease in alcohol intake disappeared with termination of VAR treatment in all alcohol reaccess cycles. The results demonstrate that VAR decreases alcohol intake during multiple cycles of alcohol reaccess following alcohol deprivation in rats and suggests that it may prevent a return to heavy alcohol drinking during a lapse from alcohol abstinence in humans with alcohol use disorder. Copyright © 2017 by the Research Society on Alcoholism.

Effects of Alcohol Intoxication and Victimization History on Women's Sexual Assault Resistance Intentions: The Role of Secondary Cognitive Appraisals

ERIC Educational Resources Information Center

Stoner, Susan A.; Norris, Jeanette; George, William H.; Davis, Kelly Cue; Masters, N. Tatiana; Hessler, Danielle M.

2007-01-01

This study used an experimental paradigm to investigate the role of secondary cognitive appraisals in women's sexual assault resistance and whether these appraisals mediated influences of alcohol and prior victimization. After consuming a beverage (control, placebo, moderate, or high dose), 351 women projected themselves into a simulated…

Exploiting Redundant Measurement of Dose and Developmental Outcome: New Methods from the Behavioral Teratology of Alcohol.

ERIC Educational Resources Information Center

Bookstein, Fred L.; And Others

1996-01-01

Discusses the use of new statistical procedures in a study of the enduring effects of prenatal alcohol exposure upon the neurobehavioral development of some 500 children born in 1975-76. Explains how the Partial Least Squares (PLS) methodology can summarize the data powerfully while avoiding familiar inferential pitfalls. (MDM)

Effect of Low (5 mg) vs. High (20-40 mg) Rosuvastatin Dose on 24h Arterial Stiffness, Central Haemodynamics, and Non-Alcoholic Fatty Liver Disease in Patients with Optimally Controlled Arterial Hypertension.

PubMed

Mitsiou, Eudoxia; Boutari, Chrysoula; Kotsis, Vasilios; Georgianou, Eleni; Doumas, Michael; Karagiannis, Asterios; Athyros, Vasilios G

2018-01-01

Arterial Stiffness (AS) and Non-Alcoholic Fatty Liver Diseases (NAFLD) are 2 related, prevalent, risk predictors of Cardiovascular Disease (CVD). We assessed the effect of low dose (5 mg/day) vs. high dose (20-40 mg/day) rosuvastatin on aortic elasticity and central haemodynamics as well as on NAFLD in patients with Arterial Hypertension (AH). Forty patients with optimally controlled AH were randomised to 2 rosuvastatin doses and followed for 6 months. 24h AS was assessed by Mobil-O-Graph, which calculates (adjusted for age and gender) Pulse Wave Velocity (PWV), adjusted for Heart Rate (HR) augmentation index (AIx75%) and central haemodynamics. The diagnosis of NAFLD was based on >5% liver steatosis on ultrasound and moderately elevated serum levels of liver enzymes. Both doses of rosuvastatin reduced Central Pulse Pressure (cPP), PWV and AIx75% (adjusted for HR) to normal values (p = NS adjusted for age, gender and HR). Liver enzymes were reduced in those with NAFLD to normal, but steatosis was reduced more by the 20-40 mg/day rosuvastatin dose (p=0.01) compared with the 5 mg/day dose. Both doses of rosuvastatin had a beneficial effect on AS; the high dose was more efficient in reducing PWVs and central haemodynamics, and also the high dose was more effective in ameliorating NAFLD. Given that AH control was optimal and lipid values attained targets, 4 other CVD predictors were also addressed. Larger and longer term studies are needed to demonstrate the clinical benefit of such treatment preference. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.

PubMed

Galesi, Fernanda L; Ayanwuyi, Lydia O; Mijares, Miriam Garcia; Cippitelli, Andrea; Cannella, Nazzareno; Ciccocioppo, Roberto; Ubaldi, Massimo

2016-10-05

A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

Oxytocin Reduces Ethanol Self-Administration in Mice.

PubMed

King, Courtney E; Griffin, William C; Luderman, Lauryn N; Kates, Malcolm M; McGinty, Jacqueline F; Becker, Howard C

2017-05-01

Excessive ethanol (EtOH) consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces EtOH consumption. Male C57BL/6J mice were given access to EtOH (20% v/v) using a model of binge-like drinking ("drinking in the dark") that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, EtOH (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive-ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models. Oxytocin (0, 0.3, 1, 3, or 10 mg/kg) dose dependently reduced EtOH consumption (maximal 45% reduction) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin's effect was blocked by pretreatment with an oxytocin receptor antagonist, and the pattern of contacts (licks) at the EtOH bottle suggested a reduction in motivation to drink EtOH. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for EtOH and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for EtOH at doses that did not alter responding for sucrose. These results indicate that oxytocin reduces EtOH consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for EtOH at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Nevertheless, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder. Copyright © 2017 by the Research Society on Alcoholism.

Psychosis induced by the interaction between disulfiram and methylphenidate may be dose dependent.

PubMed

Grau-López, Lara; Roncero, Carlos; Navarro, Maria C; Casas, Miquel

2012-01-01

There are few studies describing psychiatric symptoms occurring when methylphenidate and disulfiram are used together. The authors report a case of disulfiram and methylphenidate interaction in which psychotic symptoms could be dose dependent. The patient, diagnosed of alcohol and cocaine dependence and attention deficit hyperactivity disorder (ADHD), started treatment with methylphenidate increasing doses and disulfiram 250 mg/day over 4 weeks. During the first 2 weeks at doses of 36 mg/day of methylphenidate and maintaining disulfiram, side effects were not observed. However, by increasing to 54 mg/day, psychotic symptoms were detected. The authors reported that the effects are dose dependent. This is the first report about dose-dependent side effects in substance use disorder with ADHD.

Pharmaco-EEG-based assessment of the interaction between ethanol and oxcarbazepine.

PubMed

Pietrzak, Bogusława; Czarnecka, Elzbieta

2010-01-01

Oxcarbazepine is a representative molecule for a new class of anticonvulsant drugs that can treat alcohol dependence in addition to other disorders. Interestingly, the central mechanism of action in oxcarbazepine is very similar to ethanol, suggesting that these two agents may interact and cause enhanced effects in the central nervous system. In this study, we used a pharmaco-EEG method to examine the influence of oxcarbazepine on the effect of ethanol on the EEG of rabbits (midbrain reticular formation, hippocampus, frontal cortex). Oxcarbazepine was administered po as a single dose (20 mg/kg or 80 mg/kg) or repeatedly at a dose of 40 mg/kg/day for 14 days. Ethanol was injected iv at a dose of 0.8 g/kg 60 min after the administration of oxcarbazepine. Ethanol caused an increase in the low frequencies (0.5-4 Hz) in the recordings, and it caused a marked decrease in higher frequencies (13-30 Hz and 30-45 Hz). Oxcarbazepine altered the EEG pattern in rabbits; this interaction was dependent on the dose of the drug and whether it was administered as a single dose or as multiple doses. Oxcarbazepine administered at a lower dose had a synergistic effect with ethanol in the frontal cortex and midbrain reticular formation, and a similar effect was observed in the hippocampus at a higher dose. Changes in EEG recordings after the administration of oxcarbazepine alone were more pronounced after multiple administrations. The drug decreased the sensitivity of the hippocampus to ethanol, an observation that may be important for the treatment of alcohol addiction.

Hepatoprotective activity of Musa paradisiaca on experimental animal models

PubMed Central

Nirmala, M; Girija, K; Lakshman, K; Divya, T

2012-01-01

Objective To investigate the hepatoprotective activity of stem of Musa paradisiaca (M. paradisiaca) in CCl4 and paracetamol induced hepatotoxicity models in rats. Methods Hepatoprotective activity of alcoholic and aqueous extracts of stem of M. paradisiaca was demonstrated by using two experimentally induced hepatotoxicity models. Results Administration of hepatotoxins (CCl4 and paracetamol) showed significant biochemical and histological deteriorations in the liver of experimental animals. Pretreatment with alcoholic extract (500 mg/kg), more significantly and to a lesser extent the alcoholic extract (250 mg/kg) and aqueous extract (500 mg/kg), reduced the elevated levels of the serum enzymes like serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin levels and alcoholic and aqueous extracts reversed the hepatic damage towards the normal, which further evidenced the hepatoprotective activity of stem of M. paradisiaca. Conclusions The alcoholic extract at doses of 250 and 500 mg/kg, p.o. and aqueous extract at a dose of 500 mg/kg, p.o. of stem of M. paradisiaca have significant effect on the liver of CCl4 and paracetamol induced hepatotoxicity animal models. PMID:23569826

Hepatoprotective activity of Musa paradisiaca on experimental animal models.

PubMed

Nirmala, M; Girija, K; Lakshman, K; Divya, T

2012-01-01

To investigate the hepatoprotective activity of stem of Musa paradisiaca (M. paradisiaca) in CCl4 and paracetamol induced hepatotoxicity models in rats. Hepatoprotective activity of alcoholic and aqueous extracts of stem of M. paradisiaca was demonstrated by using two experimentally induced hepatotoxicity models. Administration of hepatotoxins (CCl4 and paracetamol) showed significant biochemical and histological deteriorations in the liver of experimental animals. Pretreatment with alcoholic extract (500 mg/kg), more significantly and to a lesser extent the alcoholic extract (250 mg/kg) and aqueous extract (500 mg/kg), reduced the elevated levels of the serum enzymes like serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin levels and alcoholic and aqueous extracts reversed the hepatic damage towards the normal, which further evidenced the hepatoprotective activity of stem of M. paradisiaca. The alcoholic extract at doses of 250 and 500 mg/kg, p.o. and aqueous extract at a dose of 500 mg/kg, p.o. of stem of M. paradisiaca have significant effect on the liver of CCl4 and paracetamol induced hepatotoxicity animal models.

Acute Effects of Alcohol on Encoding and Consolidation of Memory for Emotional Stimuli

PubMed Central

Weafer, Jessica; Gallo, David A.; De Wit, Harriet

2016-01-01

Objective: Acute doses of alcohol impair memory when administered before encoding of emotionally neutral stimuli but enhance memory when administered immediately after encoding, potentially by affecting memory consolidation. Here, we examined whether alcohol produces similar biphasic effects on memory for positive or negative emotional stimuli. Method: The current study examined memory for emotional stimuli after alcohol (0.8 g/kg) was administered either before stimulus viewing (encoding group; n = 20) or immediately following stimulus viewing (consolidation group; n = 20). A third group received placebo both before and after stimulus viewing (control group; n = 19). Participants viewed the stimuli on one day, and their retrieval was assessed exactly 48 hours later, when they performed a surprise cued recollection and recognition test of the stimuli in a drug-free state. Results: As in previous studies, alcohol administered before encoding impaired memory accuracy, whereas alcohol administered after encoding enhanced memory accuracy. Critically, alcohol effects on cued recollection depended on the valence of the emotional stimuli: Its memory-impairing effects during encoding were greatest for emotional stimuli, whereas its memory-enhancing effects during consolidation were greatest for emotionally neutral stimuli. Effects of alcohol on recognition were not related to stimulus valence. Conclusions: This study extends previous findings with memory for neutral stimuli, showing that alcohol differentially affects the encoding and consolidation of memory for emotional stimuli. These effects of alcohol on memory for emotionally salient material may contribute to the development of alcohol-related problems, perhaps by dampening memory for adverse consequences of alcohol consumption. PMID:26751358

Varenicline, low dose naltrexone, and their combination for heavy-drinking smokers: human laboratory findings.

PubMed

Ray, Lara A; Courtney, Kelly E; Ghahremani, Dara G; Miotto, Karen; Brody, Arthur; London, Edythe D

2014-10-01

Heavy-drinking smokers constitute a sizeable and hard-to-treat subgroup of smokers, for whom tailored smoking cessation therapies are not yet available. The present study used a double-blind, randomized, 2 × 2 medication design, testing varenicline alone (VAR; 1 mg twice daily), low dose naltrexone alone (L-NTX; 25 mg once daily), varenicline plus naltrexone, and placebo for effects on cigarette craving and subjective response to alcohol and cigarettes in a sample (n = 130) of heavy-drinking daily smokers (≥10 cigarettes/day). All participants were tested after a 9-day titration period designed to reach a steady state on the target medication. Testing was completed at 12 h of nicotine abstinence, after consuming a standard dose of alcohol (target breath alcohol concentration = 0.06 g/dl) and after smoking the first cigarette of the day. The combination of VAR + L-NTX was superior to placebo, and at times superior to monotherapy, in attenuating cigarette craving, cigarette and alcohol "high," and in reducing ad-lib consumption of both cigarettes and alcohol during the 9-day medication titration period. These preliminary findings indicate that clinical studies of the combination of VAR + L-NTX for heavy drinkers trying to quit smoking are warranted and may ultimately improve clinical care for this sizeable and treatment-resistant subgroup of smokers.

Low-Dose Alcohol Effects on Human Behavior and Performance: A Review of Post-1984 Research

DTIC Science & Technology

1994-11-01

34hangover" effects appear to be more toxicated practice" in alcohol’s performance effects, a severe in FH males (131). Second, further classifica...and piracetam . Blutalkoho124: 333-340, portation, Federal Aviation Administration, p. 1987. 1-18, 1988. 4. BAKER, S. J., G. J. CHRZAN, C. N. PARK, 14...flurazepam hierarchical patterns. A/c: Clin Exp Res 11: 243-248, and zopiclone on the performance of chronic in- 1937. somniac patients: A study of

Anabolic effect of Hibiscus rosasinensis Linn. leaf extracts in immature albino male rats.

PubMed

Olagbende-Dada, S O; Ezeobika, E N; Duru, F I

2007-01-01

Many plants remedies have been employed in solving man's health needs especially the nutritive value which enhances health living. Aphrodisiac plants are plants with anabolic properties i.e. they help in protein synthesis and enhances sexual abilities in males. They are also known as androgenic plants because their properties are similar to that of androgen a male hormone. Cold aqueous extract of Hibiscus rosasinensis leaves is reported by local traditional practioners in Western Nigeria to be aphrodisiac. To investigate the anabolic properties of Hibiscus rosasinensis. Three groups (8/group) of immature male rats of known weights were administered equal doses of aqueous (cold and hot) and alcoholic extracts of Hibiscus rosasinensis leaves for 8 weeks. The gain in body and isolated sexual organs (testis, epididymis, seminal vesicle and prostate) weights were determined after treatment and compared to the value obtained from a fourth untreated group which served as the control. Section through the testes of both the treated and untreated rats were also examined microscopically and displayed as a photomicrograph for comparism. All data were statistically analysed and displaced in graphic form. Over the 8 weeks of treatment, the control, the cold aqueous extract dosed, hot aqueous extract dosed and alcoholic extract dosed rats gained 8%, 15%, 18% and 22% in body weights respectively. The increase in the weight of testis, epididymis, seminal vesicle and prostate of the alcoholic extract dosed rats was 19%, 30%, 31% and 40% respectively. The anabolic effect of the leaf extracts of H. rosasinensis is hereby established. More work needs to be done on these leaf extracts to know their effect on the gonadotrophin hormones which regulate the activity of the androgens in relation to spermatogenesis.

Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.

PubMed

Carnicella, Sebastien; Yowell, Quinn V; Ron, Dorit

2011-01-01

Oral ethanol self-administration procedures in rats are useful preclinical tools for the evaluation of potential new pharmacotherapies as well as for the investigation into the etiology of alcohol abuse disorders and addiction. Determination of the effects of a potential treatment on a full ethanol dose-response curve should be essential to predict its clinical efficacy. Unfortunately, this approach has not been fully explored because of the aversive taste reaction to moderate to high doses of ethanol, which may interfere with consumption. In this study, we set out to determine whether a meaningful dose-response curve for oral ethanol self-administration can be obtained in rats. Long-Evans rats were trained to self-administer a 20% ethanol solution in an operant procedure following a history of excessive voluntary ethanol intake. After stabilization of ethanol self-administration, the concentration of the solution was varied from 2.5 to 60% (v/v), and operant and drinking behaviors, as well as blood ethanol concentration (BEC), were evaluated following the self-administration of a 20, 40, and 60% ethanol solution. Varying the concentration of ethanol from 2.5 to 60% after the development of excessive ethanol consumption led to a typical inverted U-shaped dose-response curve. Importantly, rats adapted their level and pattern of responding to changes in ethanol concentration to obtain a constant level of intake and BEC, suggesting that their operant behavior is mainly driven by the motivation to obtain a specific pharmacological effect of ethanol. This procedure can be a useful and straightforward tool for the evaluation of the effects of new potential pharmacotherapies for the treatment of alcohol abuse disorders. Copyright © 2010 by the Research Society on Alcoholism.

Effects of dexamphetamine with and without alcohol on simulated driving.

PubMed

Simons, Ries; Martens, Marieke; Ramaekers, Jan; Krul, Arno; Klöpping-Ketelaars, Ineke; Skopp, Gisela

2012-08-01

In party circuits dexamphetamine is frequently used in combination with alcohol. It is hypothesized that co-administration of dexamphetamine to alcohol might reduce the sedative effects of alcohol, but may potentiate risk-taking behaviour. The study was aimed at assessing the effects of alcohol, dexamphetamine and the combination of both on simulated driving and cognitive performance. Eighteen subjects participated in a randomized, crossover, placebo-controlled study employing four conditions: 10 mg dexamphetamine, 0.8 g/kg alcohol, 10 mg dexamphetamine + 0.8 g/kg alcohol, and placebo. Fundamental driving skills and risk-taking behaviour were assessed in a driving simulator. Subjects also completed vigilance and divided attention tasks, and subjective ratings. Mean BAC levels during simulated driving were between 0.91‰ and 0.64‰. Subjects using alcohol showed a significantly larger mean standard deviation of lateral position and shorter accepted gap time and distance. Use of alcohol or dexamphetamine + alcohol was associated with a higher frequency of red light running and collisions than the dexamphetamine or placebo conditions. Performance of vigilance and divided attention tasks was significantly impaired in the alcohol condition and, to a lesser degree, in the dexamphetamine + alcohol condition. Single doses of 0.8 g/kg alcohol increased risk-taking behaviours and impaired tracking, attention and reaction time during a 3-h period after drinking when BACs declined from 0.9 to 0.2 mg/ml. The stimulatory effects of co-administration of dexamphetamine 10 mg were not sufficient to overcome the impairing effects of alcohol on skills related to driving.

Desire to Drink Alcohol is Enhanced with High Caffeine Energy Drink Mixers.

PubMed

Marczinski, Cecile A; Fillmore, Mark T; Stamates, Amy L; Maloney, Sarah F

2016-09-01

Consumption of alcohol mixed with energy drinks (AmED) has been associated with a variety of risks beyond that observed with alcohol alone. Consumers of AmED beverages are more likely to engage in heavy episodic (binge) drinking. This study was to investigate whether the consumption of high caffeine energy drink mixers with alcohol would increase the desire to drink alcohol compared to the same amount of alcohol alone using a double-blind, within-subjects, placebo-controlled study design. Participants (n = 26) of equal gender who were social drinkers attended 6 double-blind dose administration sessions that involved consumption of alcohol and energy drinks, alone and in combination. On each test day, participants received 1 of 6 possible doses: (i) 1.21 ml/kg vodka + 3.63 ml/kg decaffeinated soft drink, (ii) 1.21 ml/kg vodka + 3.63 ml/kg energy drink, (iii) 1.21 ml/kg vodka + 6.05 ml/kg energy drink, (iv) 3.63 ml/kg decaffeinated soft drink, (v) 3.63 ml/kg energy drink, and (vi) 6.05 ml/kg energy drink. Following dose administration, participants repeatedly completed self-reported ratings on the Desire-for-Drug questionnaire and provided breath alcohol readings. Alcohol alone increased the subjective ratings of "desire for more alcohol" compared to placebo doses. Energy drink mixers with the alcohol increased desire for more alcohol ratings beyond that observed with alcohol alone. This study provides laboratory evidence that AmED beverages lead to greater desire to drink alcohol versus the same amount of alcohol consumed alone. The findings are consistent with results from animal studies indicating that caffeine increases the rewarding and reinforcing properties of alcohol. Copyright © 2016 by the Research Society on Alcoholism.

Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner.

PubMed

Cannady, Reginald; Fisher, Kristen R; Graham, Caitlin; Crayle, Jesse; Besheer, Joyce; Hodge, Clyde W

2017-05-01

Growing evidence indicates that drugs of abuse gain control over the individual by usurping glutamate-linked mechanisms of neuroplasticity in reward-related brain regions. Accordingly, we have shown that glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity in the amygdala is required for the positive reinforcing effects of alcohol, which underlie the initial stages of addiction. It is unknown, however, if enhanced AMPAR activity in the amygdala facilitates alcohol self-administration, which is a kernel premise of glutamate hypotheses of addiction. Here, we show that low-dose alcohol (0.6 g/kg/30 minutes) self-administration increases phosphorylation (activation) of AMPAR subtype GluA1 S831 (pGluA1 S831) in the central amygdala (CeA), basolateral amygdala and nucleus accumbens core (AcbC) of selectively bred alcohol-preferring P-rats as compared with behavior-matched (non-drug) sucrose controls. The functional role of enhanced AMPAR activity was assessed via site-specific infusion of the AMPAR positive modulator, aniracetam, in the CeA and AcbC prior to alcohol self-administration. Intra-CeA aniracetam increased alcohol-reinforced but not sucrose-reinforced responding and was ineffective following intra-AcbC infusion. Because GluA1 S831 is a Ca2+/calmodulin-dependent protein kinase II (CaMKII) substrate, we sought to determine if AMPAR regulation of enhanced alcohol self-administration is dependent on CaMKII activity. Intra-CeA infusion of the cell-permeable CaMKII peptide inhibitor myristolated autocamtide-2-related inhibitory peptide (m-AIP) dose-dependently reduced alcohol self-administration. A subthreshold dose of m-AIP also blocked the aniracetam-induced escalation of alcohol self-administration, demonstrating that AMPAR-mediated potentiation of alcohol reinforcement requires CaMKII activity in the amygdala. Enhanced activity of plasticity-linked AMPAR-CaMKII signaling in the amygdala may promote escalated alcohol use via increased positive reinforcement during the initial stages of addiction. © 2016 Society for the Study of Addiction.

Cognition, emotion, and the alcohol--aggression relationship: comment on Giancola (2000).

PubMed

Lyvers, M

2000-11-01

P. R. Giancola's (2000) thesis that the alcohol-aggression relationship can be explained by alcohol-induced disruption of executive cognitive functions mediated by the prefrontal cortex is critically examined. At moderate doses, alcohol has been reported to increase aggression in animals as diverse as fish, rats, cats, monkeys, and humans. Although alcohol depresses prefrontal cortex activity and disrupts executive cognitive performance in humans, alcohol's anxiolytic actions, and its disinhibiting effects on subcortical structures implicated in anger and aggression, may be at least as important as the higher cognitive functions cited by Giancola in accounting for the alcohol-aggression relationship. Other drugs that alter prefrontal cortex activity have also been reported to influence aggressive responding in humans and other animals, and implications of this are briefly discussed.

ACUTE ETHANOL DISRUPTS PHOTIC AND SEROTONERGIC CIRCADIAN CLOCK PHASE-RESETTING IN THE MOUSE

PubMed Central

Brager, Allison J.; Ruby, Christina L.; Prosser, Rebecca A.; Glass, J. David

2011-01-01

Background Alcohol abuse is associated with impaired circadian rhythms and sleep. Ethanol administration disrupts circadian clock phase-resetting, suggesting a mode for the disruptive effect of alcohol abuse on the circadian timing system. In this study, we extend previous work in C57BL/6J mice to: 1) characterize the SCN pharmacokinetics of acute systemic ethanol administration; 2) explore the effects of acute ethanol on photic and non-photic phase-resetting; and 2) determine if the SCN is a direct target for photic effects. Methods First, microdialysis was used to characterize the pharmacokinetics of acute i.p. injections of 3 doses of ethanol (0.5, 1.0 and 2.0 g/kg) in the mouse suprachiasmatic (SCN) circadian clock. Second, the effects of acute i.p. ethanol administration on photic phase-delays and serotonergic ([+]8-OH-DPAT-induced) phase-advances of the circadian activity rhythm were assessed. Third, the effects of reverse-microdialysis ethanol perfusion of the SCN on photic phase-resetting were characterized. Results Peak ethanol levels from the 3 doses of ethanol in the SCN occurred within 20–40 min post-injection with half-lives for clearance ranging from 0.6–1.8 hr. Systemic ethanol treatment dose-dependently attenuated photic and serotonergic phase-resetting. This treatment also did not affect basal SCN neuronal activity as assessed by Fos expression. Intra-SCN perfusion with ethanol markedly reduced photic phase-delays. Conclusions These results confirm that acute ethanol attenuates photic phase-delay shifts and serotonergic phase-advance shifts in the mouse. This dual effect could disrupt photic and non-photic entrainment mechanisms governing circadian clock timing. It is also significant that the SCN clock is a direct target for disruptive effects of ethanol on photic shifting. Such actions by ethanol could underlie the disruptive effects of alcohol abuse on behavioral, physiological, and endocrine rhythms associated with alcoholism. PMID:21463340

High-dose naltrexone therapy for cocaine-alcohol dependence.

PubMed

Schmitz, Joy M; Lindsay, Jan A; Green, Charles E; Herin, David V; Stotts, Angela L; Moeller, F Gerard

2009-01-01

This randomized, double-blind, placebo-controlled study compared the effects of high-dose (100 mg/d) naltrexone versus placebo in a sample of 87 randomized subjects with both cocaine and alcohol dependence. Medication conditions were crossed with two behavioral therapy platforms that examined whether adding contingency management (CM) that targeted cocaine abstinence would enhance naltrexone effects compared to cognitive behavioral therapy (CBT) without CM. Primary outcome measures for cocaine (urine screens) and alcohol use (timeline followback) were collected thrice-weekly during 12 weeks of treatment. Retention in treatment and medication compliance rates were low. Rates of cocaine use and drinks per day did not differ between treatment groups; however naltrexone did reduce frequency of heavy drinking days, as did CBT without CM. Notably, adding CM to CBT did not enhance treatment outcomes. These weak findings suggest that pharmacological and behavioral interventions that have shown efficacy in the treatment of a single drug dependence disorder may not provide the coverage needed when targeting dual drug dependence.

Differential Effects of Alcohol on Memory Performance in Adolescent Men and Women with a Binge Drinking History.

PubMed

Vinader-Caerols, Concepción; Talk, Andrew; Montañés, Adriana; Duque, Aránzazu; Monleón, Santiago

2017-09-01

Binge drinking (BD) is characterized by intermittent consumption of large quantities of alcohol in short periods. This pattern of drinking is prevalent among adolescents, and has been associated with undermined learning and memory ability. This study investigates the relationships between a history of BD and the effects of acute exposure to alcohol on learning and memory performance in adolescent men and women. A high, acute dose of alcohol or control refreshment was administered to a sample of 172 adolescent undergraduate students, some of which had a history of BD and others of which had refrained from alcohol consumption. Subsequently, immediate visual memory (IVM) and working memory (WM) was measured according to the Wechsler Memory Scale in females and males with different BAC (Experiment 1) and similar BAC (Experiment 2). In both experiments, IVM was reduced after acute alcohol consumption and there was no significant main effect of Drinking Pattern. Furthermore, an effect of cognitive alcohol tolerance on IVM was observed in women but not in men. WM was not affected by alcohol, but a gender difference was evident in that performance was superior in men than in women. In adolescents, IVM is more sensitive than WM to impairment by alcohol, and women are more vulnerable to the neurotoxic effects of alcohol than men, since the cognitive tolerance effect of alcohol on IVM develops in BD women but not in BD men. These findings emphasize the need to investigate the neurotoxic effects of alcohol in adolescent women. In adolescents, immediate visual memory (IVM) is more sensitive than working memory to impairment by alcohol, and women are more vulnerable to the neurotoxic effects of alcohol than men, because the cognitive tolerance effect of alcohol on IVM develops in binge drinking (BD) women but not in BD men. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.

The Effects of Alcohol Intoxication on Accuracy and the Confidence–Accuracy Relationship in Photographic Simultaneous Line‐ups

PubMed Central

Colloff, Melissa F.; Karoğlu, Nilda; Zelek, Katarzyna; Ryder, Hannah; Humphries, Joyce E.; Takarangi, Melanie K.T.

2017-01-01

Summary Acute alcohol intoxication during encoding can impair subsequent identification accuracy, but results across studies have been inconsistent, with studies often finding no effect. Little is also known about how alcohol intoxication affects the identification confidence–accuracy relationship. We randomly assigned women (N = 153) to consume alcohol (dosed to achieve a 0.08% blood alcohol content) or tonic water, controlling for alcohol expectancy. Women then participated in an interactive hypothetical sexual assault scenario and, 24 hours or 7 days later, attempted to identify the assailant from a perpetrator present or a perpetrator absent simultaneous line‐up and reported their decision confidence. Overall, levels of identification accuracy were similar across the alcohol and tonic water groups. However, women who had consumed tonic water as opposed to alcohol identified the assailant with higher confidence on average. Further, calibration analyses suggested that confidence is predictive of accuracy regardless of alcohol consumption. The theoretical and applied implications of our results are discussed.© 2017 The Authors Applied Cognitive Psychology Published by John Wiley & Sons Ltd. PMID:28781426

Comparison of dehydroepiandrosterone (DHEA) and pregnanolone with existing pharmacotherapies for alcohol abuse on ethanol- and food-maintained responding in male rats.

PubMed

Hulin, Mary W; Lawrence, Michelle N; Amato, Russell J; Weed, Peter F; Winsauer, Peter J

2015-03-01

The present study compared two putative pharmacotherapies for alcohol abuse and dependence, dehydroepiandrosterone (DHEA) and pregnanolone, with two Food and Drug Administration (FDA)-approved pharmacotherapies, naltrexone and acamprosate. Experiment 1 assessed the effects of different doses of DHEA, pregnanolone, naltrexone, and acamprosate on both ethanol- and food-maintained responding under a multiple fixed-ratio (FR)-10 FR-20 schedule, respectively. Experiment 2 assessed the effects of different mean intervals of food presentation on responding for ethanol under a FR-10 variable-interval (VI) schedule, whereas Experiment 3 assessed the effects of a single dose of each drug under a FR-10 VI-80 schedule. In Experiment 1, all four drugs dose-dependently decreased response rate for both food and ethanol, although differences in the rate-decreasing effects were apparent among the drugs. DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding, whereas the reverse was true for naltrexone. Acamprosate decreased responding for both reinforcers with equal potency. In Experiment 2, different mean intervals of food presentation significantly affected the number of food reinforcers obtained per session; however, changes in the number of food reinforcements did not significantly affect responding for ethanol. Under the FR-10 VI-80 schedule in Experiment 3, only naltrexone significantly decreased both the dose of alcohol presented and blood ethanol concentration (BEC). Acamprosate and pregnanolone had no significant effects on any of the dependent measures, whereas DHEA significantly decreased BEC, but did not significantly decrease response rate or the dose presented. In summary, DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding under a multiple FR-10 FR-20 schedule, and were more selective for decreasing ethanol self-administration than either naltrexone or acamprosate under that schedule. Experiment 2 showed that ethanol intake was relatively independent of the interval of reinforcement in the food-maintained component, and Experiment 3 showed that naltrexone was the most effective drug at the doses tested when the interval for food reinforcement was low and maintained under a variable-interval schedule. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of dehydroepiandrosterone (DHEA) and pregnanolone with existing pharmacotherapies for alcohol abuse on ethanol- and food-maintained responding in male rats

PubMed Central

Hulin, Mary W.; Lawrence, Michelle N.; Amato, Russell J.; Weed, Peter F.; Winsauer, Peter J.

2015-01-01

The present study compared two putative pharmacotherapies for alcohol abuse and dependence, dehydroepiandrosterone (DHEA) and pregnanolone, with two Food and Drug Administration (FDA)-approved pharmacotherapies, naltrexone and acamprosate. Experiment 1 assessed the effects of different doses of DHEA, pregnanolone, naltrexone, and acamprosate on both ethanol- and food-maintained responding under a multiple fixed-ratio (FR)-10 FR-20 schedule, respectively. Experiment 2 assessed the effects of different mean intervals of food presentation on responding for ethanol under an FR-10 variable-interval (VI) schedule, whereas Experiment 3 assessed the effects of a single dose of each drug under a FR-10 VI-80 schedule. In Experiment 1, all four drugs dose-dependently decreased response rate for both food and ethanol, although differences in the rate-decreasing effects were apparent among the drugs. DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding, whereas the reverse was true for naltrexone. Acamprosate decreased responding for both reinforcers with equal potency. In Experiment 2, different mean intervals of food presentation significantly affected the number of food reinforcers obtained per session; however, changes in the number of food reinforcements did not significantly affect responding for ethanol. Under the FR-10 VI-80 schedule in Experiment 3, only naltrexone significantly decreased both the dose of alcohol presented and blood ethanol concentration (BEC). Acamprosate and pregnanolone had no significant effects on any of the dependent measures, whereas DHEA significantly decreased BEC, but did not significantly decrease response rate or the dose presented. In summary, DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding under a multiple FR-10 FR-20 schedule, and were more selective for decreasing ethanol self-administration than either naltrexone or acamprosate under that schedule. Experiment 2 showed that ethanol intake was relatively independent of the density of reinforcement in the food-maintained component, and Experiment 3 showed that naltrexone was the most effective drug at the doses tested when the density for food reinforcement was low and maintained under a variable-interval schedule. PMID:25620274

Feasibility of a community intervention for the prevention of suicide and alcohol abuse with Yup'ik Alaska Native youth: the Elluam Tungiinun and Yupiucimta Asvairtuumallerkaa studies.

PubMed

Mohatt, Gerald V; Fok, Carlotta Ching Ting; Henry, David; Allen, James

2014-09-01

The Elluam Tungiinun and Yupiucimta Asvairtuumallerkaa studies evaluated the feasibility of a community intervention to prevent suicide and alcohol abuse among rural Yup'ik Alaska Native youth in two remote communities. The intervention originated in an Indigenous model of protection, and its development used a community based participatory research process. Feasibility assessment aimed to assess the extent to which (1) the intervention could be implemented in rural Alaska Native communities, and (2) the intervention was capable of producing measurable effects. Scales maximally sensitive to change were derived from earlier measurement work, and the study contrasted implementation process and outcomes across the two communities. In one community, medium dose response effects (d = .30-.50), with dose defined as number of intervention activities attended, were observed in the growth of intermediate protective factors and ultimate variables. In the other community, medium dose effects were observed for one intermediate protective factor variable, and small dose effects were observed in ultimate variables. Differences across communities in resources supporting intervention explain these contrasting outcomes. Results suggest implementation in these rural Alaska settings is feasible when sufficient resources are available to sustain high levels of local commitment. In such cases, measureable effects are sufficient to warrant a prevention trial.

Characterization of ferrous-methylthymol blue-polyvinyl alcohol gel dosimeters using nuclear magnetic resonance and optical techniques

NASA Astrophysics Data System (ADS)

Rabaeh, Khalid A.; Eyadeh, Molham M.; Hailat, Tariq F.; Aldweri, Feras M.; Alheet, Samer M.; Eid, Rania M.

2018-07-01

A new composition of Ferrous sulphate-Metheylthymol blue (MTB)-Polyvinyl alcohol (PVA) dosimeter is introduced in this work and evaluated using nuclear magnetic resonance (NMR) and absorbance spectrophotometry techniques. The Fricke-MTB-PVA dosimeters were irradiated using a medical linear accelerator in a cubic water phantom. The dose response of the dosimeters was investigated using NMR in terms of spin-spin relaxation rate (R2), and ultraviolet and visible regions (UV-Vis) spectrophotometry in terms of absorbance. The dosimeter presents a linear dose response for doses up to 20 Gy with UV-Vis and 40 Gy with NMR method. The sample with 0.1 mM MTB, 5% PVA by weight showed highest dose sensitivity for both techniques. The Fricke-MTB-PVA dosimeter developed in this work has a significant advance over the Fricke-MTB-gelatin system: the NMR sensitivity was remarkably improved; the auto-oxidation rate was seven times lower, and no significant dose rate or photon energy effects were observed.

Alcohol Consumption as a Risk Factor for Acute and Chronic Pancreatitis: A Systematic Review and a Series of Meta-analyses.

PubMed

Samokhvalov, Andriy V; Rehm, Jürgen; Roerecke, Michael

2015-12-01

Pancreatitis is a highly prevalent medical condition associated with a spectrum of endocrine and exocrine pancreatic insufficiencies. While high alcohol consumption is an established risk factor for pancreatitis, its relationship with specific types of pancreatitis and a potential threshold have not been systematically examined. We conducted a systematic literature search for studies on the association between alcohol consumption and pancreatitis based on PRISMA guidelines. Non-linear and linear random-effect dose-response meta-analyses using restricted cubic spline meta-regressions and categorical meta-analyses in relation to abstainers were conducted. Seven studies with 157,026 participants and 3618 cases of pancreatitis were included into analyses. The dose-response relationship between average volume of alcohol consumption and risk of pancreatitis was monotonic with no evidence of non-linearity for chronic pancreatitis (CP) for both sexes (p = 0.091) and acute pancreatitis (AP) in men (p = 0.396); it was non-linear for AP in women (p = 0.008). Compared to abstention, there was a significant decrease in risk (RR = 0.76, 95%CI: 0.60-0.97) of AP in women below the threshold of 40 g/day. No such association was found in men (RR = 1.1, 95%CI: 0.69-1.74). The RR for CP at 100 g/day was 6.29 (95%CI: 3.04-13.02). The dose-response relationships between alcohol consumption and risk of pancreatitis were monotonic for CP and AP in men, and non-linear for AP in women. Alcohol consumption below 40 g/day was associated with reduced risk of AP in women. Alcohol consumption beyond this level was increasingly detrimental for any type of pancreatitis. The work was financially supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (R21AA023521) to the last author.

Differential Effects of Alcohol on Working Memory: Distinguishing Multiple Processes

PubMed Central

Saults, J. Scott; Cowan, Nelson; Sher, Kenneth J.; Moreno, Matthew V.

2008-01-01

We assessed effects of alcohol consumption on different types of working memory (WM) tasks in an attempt to characterize the nature of alcohol effects on cognition. The WM tasks varied in two properties of materials to be retained in a two-stimulus comparison procedure. Conditions included (1) spatial arrays of colors, (2) temporal sequences of colors, (3) spatial arrays of spoken digits, and (4) temporal sequences of spoken digits. Alcohol consumption impaired memory for auditory and visual sequences, but not memory for simultaneous arrays of auditory or visual stimuli. These results suggest that processes needed to encode and maintain stimulus sequences, such as rehearsal, are more sensitive to alcohol intoxication than other WM mechanisms needed to maintain multiple concurrent items, such as focusing attention on them. These findings help to resolve disparate findings from prior research into alcohol’s effect on WM and on divided attention. The results suggest that moderate doses of alcohol impair WM by affecting certain mnemonic strategies and executive processes rather than by shrinking the basic holding capacity of WM. PMID:18179311

mTOR activation is required for the anti-alcohol effect of ketamine, but not memantine, in alcohol-preferring rats

PubMed Central

Sabino, Valentina; Narayan, Aditi R.; Zeric, Tamara; Steardo, Luca; Cottone, Pietro

2013-01-01

Glutamate NMDA receptors mediate many molecular and behavioral effects of alcohol, and they play a key role in the development of excessive drinking. Uncompetitive NMDA receptor antagonists may, therefore, have therapeutic potential for alcoholism. The first aim was to compare the effects of the NMDA antagonists memantine and ketamine on ethanol and saccharin drinking in alcohol-preferring rats. The second aim was to determine whether the effects of the two NMDA receptor antagonists were mediated by the mammalian target of rapamycin (mTOR). TSRI Sardinian alcohol-preferring rats were allowed to self-administer either 10% w/v ethanol or 0.08% w/v saccharin, and water. Operant responding and motor activity were assessed following administration of either memantine (0–10 mg/kg) or ketamine (0–20 mg/kg). Finally, ethanol self-administration was assessed in rats administered with either memantine or ketamine but pretreated with the mTOR inhibitor rapamycin (2.5 mg/kg). The uncompetitive NMDA receptor antagonists memantine and ketamine dose-dependently reduced ethanol drinking in alcohol-preferring rats; while memantine had a preferential effect on alcohol over saccharin, ketamine reduced responding for both solutions. Neither antagonist induced malaise, as shown by the lack of effect on water intake and motor activity. The mTOR inhibitor rapamycin blocked the effects of ketamine, but not those of memantine. Memantine and ketamine both reduce alcohol drinking in alcohol-preferring rats, but only memantine is selective for alcohol. The effects of ketamine, but not memantine, are mediated by mTOR. The results support the therapeutic potential of uncompetitive NMDA receptor antagonists, especially memantine, in alcohol addiction. PMID:23466691

Response to Alcohol in Women: Role of the Menstrual Cycle and a Family History of Alcoholism

PubMed Central

Evans, Suzette M.; Levin, Frances R.

2010-01-01

The present study determined whether: 1) the response to alcohol varied as a function of menstrual cycle phase and 2) women with a paternal history of alcoholism (FHP) were less sensitive to the effects of alcohol compared to women without a family history of alcoholism (FHN). The behavioral effects of alcohol (0.00, 0.25, 0.75 g/kg) were evaluated in 21 FHN and 24 FHP women; each dose was tested during both the midfollicular and late luteal phases of the menstrual cycle. Baseline negative mood was increased during the luteal phase compared to the follicular phase (increased Beck Depression scores and decreased Vigor, Arousal, and Friendly scores). Alcohol increased ratings of Drug Liking and Good Drug Effect more in the luteal phase than the follicular phase. FHP women had greater negative mood during the luteal phase and some of these dysphoric effects were increased by alcohol more in FHP women than FHN women. Alcohol impaired performance, with no group or menstrual cycle differences. However, consistent with previous studies, FHP women were less impaired by alcohol than FHN women on the balance task. These data indicate that 1) the differences in response to alcohol across the menstrual cycle are subtle, although alcohol is liked more during the luteal phase; 2) increases in dysphoric mood during the luteal phase are more pronounced in FHP women compared to FHN women, particularly after alcohol; and 3) the differences observed in response to alcohol between FHP and FHN women are less pronounced than previously shown in men. PMID:20888148

Complex interactions between the subject factors of biological sex and prior histories of binge-drinking and unpredictable stress influence behavioral sensitivity to alcohol and alcohol intake.

PubMed

Quadir, Sema G; Guzelian, Eugenie; Palmer, Mason A; Martin, Douglas L; Kim, Jennifer; Szumlinski, Karen K

2017-08-10

Alcohol use disorders, affective disorders and their comorbidity are sexually dimorphic in humans. However, it is difficult to disentangle the interactions between subject factors influencing alcohol sensitivity in studies of humans. Herein, we combined murine models of unpredictable, chronic, mild stress (UCMS) and voluntary binge-drinking to examine for sex differences in the interactions between prior histories of excessive ethanol-drinking and stress upon ethanol-induced changes in motor behavior and subsequent drinking. In Experiment 1, female mice were insensitive to the UCMS-induced increase in ethanol-induced locomotion and ethanol intake under continuous alcohol-access. Experiment 2 revealed interactions between ethanol dose and sex (females>males), binge-drinking history (water>ethanol), and UCMS history (UCMS>controls), with no additive effect of a sequential prior history of both binge drinking and UCMS observed. We also observed an interaction between UCMS history and sex for righting recovery. UCMS history potentiated subsequent binge-drinking in water controls of both sexes and in male binge-drinking mice. Conversely, a prior binge-drinking history increased subsequent ethanol intake in females only, irrespective of prior UCMS history. In Experiment 3, a concurrent history of binge-drinking and UCMS did not alter ethanol intake, nor did it influence the ethanol dose-locomotor response function, but it did augment alcohol-induced sedation and reduced subsequent alcohol intake over that produced by binge-drinking alone. Thus, the subject factors of biological sex, prior stressor history and prior binge-drinking history interact in complex ways in mice to impact sensitivity to alcohol's motor-stimulating, -incoordinating and intoxicating effects, as well as to influence subsequent heavy drinking. Copyright © 2017 Elsevier Inc. All rights reserved.

The Effects of Atropine Sulfate on Aviator Performance

DTIC Science & Technology

1985-03-01

and Environmental Medicine , !_6(3), 30*4-308. 8. Asknes, 3. 0. (195*4). Effects of small doses of alcohol upon performance in a Link trainer. Journal...of Aviation Medicine , 25, 680-688. 9.- Henry, P. H., Davis, To Q., Engelken, 3. J.p Triebvasserg Jo H., &Lancaster, M. C. (1974). Alcohol-induced...performance decrements assessed by two Link trainer tasks using experienced pilots. Aerospace Medicine , *45(10), 1180-1189. 10. Henry, P. H., Flueok, J. A

Mixing an energy drink with an alcoholic beverage increases motivation for more alcohol in college students.

PubMed

Marczinski, Cecile A; Fillmore, Mark T; Henges, Amy L; Ramsey, Meagan A; Young, Chelsea R

2013-02-01

There has been a dramatic rise in the consumption of alcohol mixed with energy drinks (AmEDs) in social drinkers. It has been suggested that AmED beverages might lead individuals to drink greater quantities of alcohol. This experiment was designed to investigate whether the consumption of AmEDs would alter alcohol priming (i.e., increasing ratings of wanting another drink) compared with alcohol alone. Participants (n = 80) of equal gender attended 1 session where they were randomly assigned to receive 1 of 4 doses (0.91 ml/kg vodka, 1.82 ml/kg energy drink, 0.91 ml/kg vodka mixed with 1.82 ml/kg energy drink [AmED], or a placebo beverage). Alcohol-induced priming of the motivation to drink was assessed by self-reported ratings on the Desire for Drug questionnaire. The priming dose of alcohol increased the subjective ratings of "desire" for more alcohol, consistent with previous research that small doses of alcohol can increase the motivation to drink. Furthermore, higher desire ratings over time were observed with AmEDs compared with alcohol alone. Finally, ratings of liking the drink were similar for the alcohol and AmED conditions. An energy drink may elicit increased alcohol priming. This study provides laboratory evidence that AmED beverages may lead to greater motivation to drink versus the same amount of alcohol consumed alone. Copyright © 2012 by the Research Society on Alcoholism.

Adolescent C57BL/6J mice show elevated alcohol intake, but reduced taste aversion, as compared to adult mice: a potential behavioral mechanism for binge drinking.

PubMed

Holstein, Sarah E; Spanos, Marina; Hodge, Clyde W

2011-10-01

Binge alcohol drinking during adolescence is a serious health problem that may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge-like alcohol intake, limited-access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge-like alcohol drinking using a limited-access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol-induced conditioned taste aversion (CTA). Binge-like alcohol consumption was investigated in adolescent (4 weeks) and adult (10 weeks) male C57BL/6J mice for 2 to 4 h/d for 16 days. Developmental differences in sensitivity to an alcohol-induced CTA were examined in adolescent and adult mice, with saline or alcohol (3 or 4 g/kg) repeatedly paired with the intake of a novel tastant (NaCl). Adolescent mice showed a significant increase in alcohol intake as compared to adults, with adolescents achieving higher BACs and increasing alcohol consumption over successive cycles of the binge procedure. Conversely, adolescent mice exhibited a dose-dependent reduction in sensitivity to the aversive properties of alcohol, as compared to adult mice, with adolescent mice failing to develop a CTA to 3 g/kg alcohol. Finally, extinction of an alcohol CTA was observed following conditioning with a higher dose of alcohol in adolescent, versus adult, mice. These results indicate that adolescent mice consume more alcohol, per kilogram body weight, than adults in a binge-like model of alcohol drinking and demonstrate a blunted sensitivity to the conditioned aversive effects of alcohol. Overall, this supports a behavioral framework by which heightened binge alcohol intake during adolescence occurs, in part, via a reduced sensitivity to the aversive properties of alcohol. Copyright © 2011 by the Research Society on Alcoholism.

Viral-mediated knockdown of mGluR7 in the nucleus accumbens mediates excessive alcohol drinking and increased ethanol-elicited conditioned place preference in rats.

PubMed

Bahi, Amine

2013-10-01

Whether metabotropic glutamate 7 (mGluR7) -activation enhances or diminishes the reinforcing properties of psychostimulants remains unclear. We have previously shown that systemic mGluR7 activation reduced alcohol consumption and preference as well as locomotor-stimulating and rewarding properties of ethanol. In this study, we further examined the contribution of mGluR7 on the effect of ethanol within the nucleus accumbens (NAcc), a neural target for many drugs of abuse. Using short hairpin RNA (shRNA)-expressing lentiviral vectors (LV) to alter locally the activity of mGluR7 in male rats, we have shown that blocking mGluR7 expression increased ethanol consumption and preference in a two-bottle choice drinking paradigm with no effect either on saccharin or on quinine used for taste discrimination. In addition, mGluR7 knockdown increases preference for environments previously paired with low doses of ethanol in the conditioned place preference (CPP) test, as it shifted the dose-response curve for ethanol CPP to the left, indicating alterations in the rewarding effects of alcohol. More importantly, mGluR7 blockade in the dorsal striatum (DS) neither affected ethanol consumption nor ethanol-elicited CPP. These results show that levels of mGluR7 in the NAcc regulate responsiveness to alcohol. Taken together, these findings clearly demonstrate that mGluR7 signaling within the NAcc is a key modulator of functional responses to ethanol and offer an important target for regulating the addictive effects of alcohol.

Melatonin and vitamin C attenuates alcohol-induced oxidative stress in aorta.

PubMed

Sönmez, Mehmet Fatih; Narin, Figen; Balcioğlu, Esra

2009-12-01

Epidemiological studies have shown that low to moderate doses of alcohol consumption are beneficial to cardiac health. However, chronic high doses of alcohol ingestion cause cardiovascular complications. The aim of this study was to investigate both the effects of melatonin and vitamin C and expression of endothelial nitric oxide synthase in aorta of chronic alcoholic rats. Twenty-four adult male Wistar rats weighing 200-250 g were used in the study. Rats were divided into four equal groups. Group I (control): rats were not fed on alcohol; Group II: rats were fed on alcohol; Group III: rats were fed on alcohol and 40 mg/kg vitamin C were injected intraperitoneally and Group IV: rats were fed on alcohol and 4 mg/kg melatonin were injected intraperitoneally. At the end of the experiment, rats were killed and aorta tissues were removed. Some parts of the aorta tissues were used for biochemical analyses and the other parts were used at histological procedures. In the control group, endothelial nitric oxide synthase immunoreactivity was (++) in smooth muscle cells and endothelial cells. Expression of endothelial nitric oxide synthase in the alcohol group was stronger than control group. Chronic ethanol ingestion significantly increased (p < 0.05); and melatonin significantly decreased both the plasma and tissue malondialdehyde levels. The superoxide dismutase levels and catalase activity did not change significantly in the Vitamin C and melatonin groups (p > 0.05) compared to the control and alcohol groups. The present results indicate that chronic alcohol consumption increase lipid peroxidation and cause endothelial nitric oxide synthase expression in the aorta. However, melatonin and vitamin C administration provide partial protection against alcohol-induced damage.

Serum levels of brain-derived neurotrophic factor in alcohol-dependent patients receiving high-dose baclofen.

PubMed

Geisel, Olga; Hellweg, Rainer; Müller, Christian A

2016-06-30

The neurotrophin brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the development and maintenance of addictive and other psychiatric disorders. Also, interactions of γ-aminobutyric acid (GABA)-ergic compounds and BDNF have been reported. The objective of this study was to investigate serum levels of BDNF over time in alcohol-dependent patients receiving individually titrated high-dose treatment (30-270mg/d) with the GABA-B receptor agonist baclofen or placebo for up to 20 weeks. Serum levels of BDNF were measured in patients of the baclofen/placebo group at baseline (t0), 2 weeks after reaching individual high-dose of baclofen/placebo treatment (t1) and after termination of study medication (t2) in comparison to carefully matched healthy controls. No significant differences in serum levels of BDNF between the baclofen and the placebo group or healthy controls were found at t0, t1, or at t2. Based on these findings, it seems unlikely that baclofen exerts a direct effect on serum levels of BDNF in alcohol-dependent patients. Future studies are needed to further explore the mechanism of action of baclofen and its possible relationship to BDNF in alcohol use disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

"High" motivation for alcohol: what are the practical effects of energy drinks on alcohol priming?

PubMed

Peacock, Amy; Bruno, Raimondo

2013-02-01

While several researchers have proposed a causal relationship between alcohol mixed with energy drink (AmED) consumption and subsequent alcohol intake, there is a dearth of research exploring the potential mechanisms underpinning this association. Marczinski and colleagues (in press) report the results of a double-blind, placebo-controlled, between-groups study assessing whether an initial AmED dose primes an increased motivation to drink relative to alcohol alone. Participants (n = 80) received either alcohol (0.91 ml/kg vodka), energy drink (ED; 1.82 ml/kg Red Bull(®) ), AmED, or a placebo beverage and then self-reported their motivation to drink via the Desire-for-Drug scale. Subjective ratings of "desire more alcohol" were significantly higher than predrink in the placebo, alcohol, and AmED conditions, with this effect apparent at more time points in the AmED condition. While it was concluded that EDs may increase alcohol priming, between-condition analyses revealed that ratings did not differ significantly in AmED and alcohol conditions, with moderate magnitude treatment effects at most, and ratings of desire generally closer to 0 (absence of desire) than 100 (very much desire). While the study by Marczinski and colleagues fills an important gap in the literature, direct measurement of AmED priming's effect on subsequent alcohol consumption using a within-subjects design and appropriate statistical comparison is required to (i) establish the practical implications of these results for AmED consumers and (ii) discount any individual differences in such priming effects. Copyright © 2012 by the Research Society on Alcoholism.

INTERACTIONS BETWEEN AGE AND MODERATE ALCOHOL EFFECTS ON SIMULATED DRIVING PERFORMANCE

PubMed Central

Sklar, Alfredo L.; Boissoneault, Jeff; Fillmore, Mark T.; Nixon, Sara Jo

2013-01-01

Rationale There is a substantial body of literature documenting the deleterious effects of both alcohol consumption and age on driving performance. There is, however, limited work examining the interaction of age and acute alcohol consumption. Objectives The current study was conducted to determine if moderate alcohol doses differentially affect the driving performance of older and younger adults. Methods Healthy older (55 – 70) and younger (25 – 35) adults were tested during a baseline session and again following consumption of one of three beverages (0.0% (placebo), 0.04% or 0.065% target breath alcohol concentration). Measures of driving precision and average speed were recorded. Results Older adults performed more poorly on precision driving measures and drove more slowly than younger adults at baseline. After controlling for baseline performance, interactions between alcohol and age were observed following beverage consumption on two measures of driving precision with older adults exhibiting greater impairment as a result of alcohol consumption. Conclusions These data provide evidence that older adults may be more susceptible to the effects of alcohol on certain measures of driving performance. An investigation of mechanisms accounting for alcohol’s effects on driving in older and younger adults is required. Further evaluation using more complex driving environments is needed to assess the real-world implication of this interaction. PMID:24030469

Lipid metabolism abnormalities in alcohol-treated rabbits: a morphometric and haematologic study comparing high and low alcohol doses.

PubMed

Ikemura, Satoshi; Yamamoto, Takuaki; Motomura, Goro; Iwasaki, Kenyu; Yamaguchi, Ryosuke; Zhao, Garida; Iwamoto, Yukihide

2011-08-01

The pathogenesis of alcohol-induced osteonecrosis remains unclear. The purpose of the present study was to evaluate the morphological changes in bone marrow fat cells and the changes in the serum lipid levels in alcohol-treated rabbits. Fifteen rabbits were randomly assigned into three groups: Four rabbits intragastrically received low-dose alcohol (LDA) (15 ml/kg per day) containing 15% ethanol for 4 weeks, five rabbits received high-dose alcohol (HDA) (30 ml/kg per day) for 4 weeks and six rabbits received physiologic saline for 4 weeks as a control group. Six weeks after the initial alcohol administration, all rabbits were sacrificed. The mean size of the bone marrow fat cells in rabbits treated with HDA was significantly larger than that in the control group (P = 0.0001). Haematologically, the levels of triglycerides and free fatty acids in the rabbits treated with both low-dose and HDA were significantly higher than those in the control group (P = 0.001 for both comparisons). The results of this study are that there are lipid metabolism abnormalities, both morphologically and haematologically, after alcohol administration. Also these findings were more apparent in rabbits treated with HDA than those treated with LDA. © 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.

Cellular and molecular mechanisms of alcohol-induced osteopenia.

PubMed

Luo, Zhenhua; Liu, Yao; Liu, Yitong; Chen, Hui; Shi, Songtao; Liu, Yi

2017-12-01

Alcoholic beverages are widely consumed, resulting in a staggering economic cost in different social and cultural settings. Types of alcohol consumption vary from light occasional to heavy, binge drinking, and chronic alcohol abuse at all ages. In general, heavy alcohol consumption is widely recognized as a major epidemiological risk factor for chronic diseases and is detrimental to many organs and tissues, including bones. Indeed, recent findings demonstrate that alcohol has a dose-dependent toxic effect in promoting imbalanced bone remodeling. This imbalance eventually results in osteopenia, an established risk factor for osteoporosis. Decreased bone mass and strength are major hallmarks of osteopenia, which is predominantly attributed not only to inhibition of bone synthesis but also to increased bone resorption through direct and indirect pathways. In this review, we present knowledge to elucidate the epidemiology, potential pathogenesis, and major molecular mechanisms and cellular effects that underlie alcoholism-induced bone loss in osteopenia. Novel therapeutic targets for correcting alcohol-induced osteopenia are also reviewed, such as modulation of proinflammatory cytokines and Wnt and mTOR signaling and the application of new drugs.

Alterations of reward mechanisms in bulbectomised rats.

PubMed

Grecksch, Gisela; Becker, Axel

2015-06-01

The positive association between alcoholism and depression is a common clinical observation. We investigated the relationship between depression and reward mechanisms using a validated animal model for depressive-like behaviour, the olfactory bulbectomy in rats. The effects of bilateral olfactory bulbectomy on reward mechanisms were studied in two different experimental paradigms - the voluntary self-administration of ethanol and the conditioned place preference to alcohol injection and compared to the effects of ethanol on locomotor activity and body core temperature. The voluntary ethanol intake was increased significantly in bulbectomised rats in a drinking experiment and also after a period of abstinence. Conditioned place preference (CPP) was induced in all animals. However, bulbectomised rats needed a higher dose of alcohol to produce CPP. The sedative effect of ethanol on locomotor activity was reduced in bulbectomised animals. Measurement of body temperature revealed a dose-dependent hypothermic effect of ethanol in both groups. These results suggest that the reward mechanisms may be altered in this animal model as a common phenomenon associated with depression. Furthermore, they support the hypothesis that the addictive and/or rewarding properties of some drugs of abuse may be modified in depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Static posturography and intravenous alcohol.

PubMed

Uimonen, S; Laitakari, K; Bloigu, R; Reinilä, M; Sorri, M

1994-01-01

Twelve health subjects were assessed using static posturography before and after intravenous alcohol infusion in a double-blind experiment. The dose was 0.5 g ethanol per kg body weight in 15 minutes, which raised the blood alcohol concentration to a level of approximately 1 mg/mL. Among other parameters, the average body sway velocity (BSV) and area of body sway (BSA) were measured. BSV was the most sensitive parameter for detecting increased body sway after alcohol infusion, and a significant effect of alcohol on its values was seen at 0.46 to 1.0 mg/mL alcohol concentrations. The second best indicator was the BSA. There was a positive correlation between the BSV and the BSA. The other parameters were not affected. The Romberg quotient remained constant during the alcohol test. The test battery used was relevant to distinguish the effect of alcohol on balance. In this study, acute blood alcohol concentrations of around 0.5 to 1.0 mg/mL affected BSV more significantly than BSA. The authors do not, however, recommend the test for forensic purposes in examining drivers with alcohol in their blood, as there is too much interindividual dispersion in the results.

Effects of the novel endocannabinoid uptake inhibitor, LY2183240, on fear-potentiated startle and alcohol-seeking behaviors in mice selectively bred for high alcohol preference.

PubMed

Powers, Matthew S; Barrenha, Gustavo D; Mlinac, Nate S; Barker, Eric L; Chester, Julia A

2010-12-01

Alcohol-use disorders often occur together with anxiety disorders in humans which may be partly due to common inherited genetic factors. Evidence suggests that the endocannabinoid system (ECS) is a promising therapeutic target for the treatment of individuals with anxiety and/or alcohol-use disorders. The present study assessed the effects of a novel endocannabinoid uptake inhibitor, LY2183240, on anxiety- and alcohol-seeking behaviors in a unique animal model that may represent increased genetic risk to develop co-morbid anxiety and alcohol-use disorders in humans. Mice selectively bred for high alcohol preference (HAP) show greater fear-potentiated startle (FPS) than mice selectively bred for low alcohol preference (LAP). We examined the effects of LY2183240 on the expression of FPS in HAP and LAP mice and on alcohol-induced conditioned place preference (CPP) and limited-access alcohol drinking behavior in HAP mice. Repeated administration of LY2183240 (30 mg/kg) reduced the expression of FPS in HAP but not LAP mice when given prior to a second FPS test 48 h after fear conditioning. Both the 10 and 30 mg/kg doses of LY2183240 enhanced the expression of alcohol-induced CPP and this effect persisted in the absence of the drug. LY2183240 did not alter limited-access alcohol drinking behavior, unconditioned startle responding, or locomotor activity. These findings suggest that ECS modulation influences both conditioned fear and conditioned alcohol reward behavior. LY2183240 may be an effective pharmacotherapy for individuals with anxiety disorders, such as post-traumatic stress disorder, but may not be appropriate for individuals with co-morbid anxiety and alcohol-use disorders.

Adolescent C57BL/6J mice show elevated alcohol intake, but reduced taste aversion, as compared to adult mice: a potential behavioral mechanism for binge drinking

PubMed Central

Holstein, Sarah E.; Spanos, Marina; Hodge, Clyde W.

2011-01-01

Background Binge alcohol drinking during adolescence is a serious health problem which may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge-like alcohol intake, limited-access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge-like alcohol drinking using a limited-access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol-induced conditioned taste aversion (CTA). Methods Binge-like alcohol consumption was investigated in adolescent (4 wk) and adult (10 wk) male C57BL/6J mice for 2-4 h/day for 16 d. Developmental differences in sensitivity to an alcohol-induced CTA were examined in adolescent and adult mice, with saline or alcohol (3 or 4 g/kg) repeatedly paired with intake of a novel tastant (NaCl). Results Adolescent mice showed a significant increase in alcohol intake as compared to adults, with adolescents achieving higher BACs and increasing alcohol consumption over successive cycles of the binge procedure. Conversely, adolescent mice exhibited a dose-dependent reduction in sensitivity to the aversive properties of alcohol, as compared to adult mice, with adolescent mice failing to develop a CTA to 3 g/kg alcohol. Finally, extinction of an alcohol CTA was observed following conditioning with a higher dose of alcohol in adolescent, versus adult, mice. Conclusions These results indicate that adolescent mice consume more alcohol, per kg body weight, than adults in a binge-like model of alcohol drinking, and demonstrate a blunted sensitivity to the conditioned aversive effects of alcohol. Overall, this supports a behavioral framework by which heightened binge alcohol intake during adolescence occurs, in part, via a reduced sensitivity to the aversive properties of alcohol. PMID:21575017

Baclofen to prevent agitation in alcohol-addicted patients in the ICU: study protocol for a randomised controlled trial.

PubMed

Vourc'h, Mickael; Feuillet, Fanny; Mahe, Pierre-Joachim; Sebille, Véronique; Asehnoune, Karim

2016-08-19

Alcohol is the leading psychoactive substance consumed in France, with about 15 million regular consumers. The National institute on Alcohol Abuse and Alcoholism (NIAAA) considers alcohol abuse to be more than 14 units of alcohol a week for men and 7 units for women. The specific complication of alcoholism is the alcohol withdrawal syndrome. Its incidence reaches up to 30 % and its main complications are delirium tremens, restlessness, extended hospital stay, higher morbidity, and psychiatric and cognitive impairment. Without appropriate treatment, delirium tremens can lead to death in up to 50 % of patients. This prospective, double-blind, randomised controlled study versus placebo will be conducted in twelve French intensive care units (ICU). Patients with an alcohol intake level higher than the NIAAA threshold, who are under mechanical ventilation, will be included. The primary objective is to determine whether baclofen is more efficient than placebo in preventing restlessness-related side effects in the ICU. Secondary outcomes include mechanical ventilation duration, length of ICU stay, and cumulative doses of sedatives and painkillers received within 28 days of ICU admission. Restlessness-related side effects in the ICU are defined as unplanned extubation, medical disposal removal (such as urinary catheter, venous or arterial line or surgical drain), falling out of bed, ICU runaway (leaving ICU without physician's approval), immobilisation device removal, self-aggression or aggression towards medical staff. Daily doses of baclofen/placebo will be guided by daily creatinine clearance assessment. Restlessness in alcoholic patients is a life-threatening issue in ICUs. BACLOREA is a randomised study assessing the capacity of baclofen to prevent agitation in mechanically ventilated patients. Enrolment of 314 patients will begin in June 2016 and is expected to end in October 2018. ClinicalTrials.gov Identifier: NCT02723383 , registered on 3 March 2016.

αCaMKII Autophosphorylation Controls the Establishment of Alcohol Drinking Behavior

PubMed Central

Easton, Alanna C; Lucchesi, Walter; Lourdusamy, Anbarasu; Lenz, Bernd; Solati, Jalal; Golub, Yulia; Lewczuk, Piotr; Fernandes, Cathy; Desrivieres, Sylvane; Dawirs, Ralph R; Moll, Gunther H; Kornhuber, Johannes; Frank, Josef; Hoffmann, Per; Soyka, Michael; Kiefer, Falk; Schumann, Gunter; Peter Giese, K; Müller, Christian P

2013-01-01

The α-Ca2+/calmodulin-dependent protein kinase II (αCaMKII) is a crucial enzyme controlling plasticity in the brain. The autophosphorylation of αCaMKII works as a ‘molecular memory' for a transient calcium activation, thereby accelerating learning. We investigated the role of αCaMKII autophosphorylation in the establishment of alcohol drinking as an addiction-related behavior in mice. We found that alcohol drinking was initially diminished in αCaMKII autophosphorylation-deficient αCaMKIIT286A mice, but could be established at wild-type level after repeated withdrawals. The locomotor activating effects of a low-dose alcohol (2 g/kg) were absent in αCaMKIIT286A mice, whereas the sedating effects of high-dose (3.5 g/kg) were preserved after acute and subchronic administration. The in vivo microdialysis revealed that αCaMKIIT286A mice showed no dopamine (DA) response in the nucleus accumbens to acute or subchronic alcohol administration, but enhanced serotonin (5-HT) responses in the prefrontal cortex. The attenuated DA response in αCaMKIIT286A mice was in line with altered c-Fos activation in the ventral tegmental area after acute and subchronic alcohol administration. In order to compare findings in mice with the human condition, we tested 23 single-nucleotide polymorphisms (SNPs) in the CAMK2A gene for their association with alcohol dependence in a population of 1333 male patients with severe alcohol dependence and 939 controls. We found seven significant associations between CAMK2A SNPs and alcohol dependence, one of which in an autophosphorylation-related area of the gene. Together, our data suggest αCaMKII autophosphorylation as a facilitating mechanism in the establishment of alcohol drinking behavior with changing the DA–5-HT balance as a putative mechanism. PMID:23459588

Association between alcohol consumption and the risk of incident type 2 diabetes: a systematic review and dose-response meta-analysis.

PubMed

Li, Xiao-Hua; Yu, Fei-Fei; Zhou, Yu-Hao; He, Jia

2016-03-01

Previous cohort studies have shown that moderate alcohol consumption was associated with a lower risk of type 2 diabetes (T2D). However, whether these associations differ according to the characteristics of patients with T2D remains controversial. The purpose of this study was to explore and summarize the evidence on the strength of the association between alcohol consumption and the subsequent risk of T2D by using a dose-response meta-analytic approach. We identified potential studies by searching the PubMed, Embase, and Cochrane Library databases up to 24 March 2015. Prospective observational studies that evaluated the relation between alcohol consumption and the risk of T2D and reported its effect estimates with 95% CIs were included. Analyses were based on 706,716 individuals (275,711 men and 431,005 women) from 26 studies with 31,621 T2D cases. We detected a nonlinear relation between alcohol consumption and the risk of T2D, which was identified in all cohorts (P-trend < 0.001, P-nonlinearity < 0.001), in men (P-trend < 0.001, P-nonlinearity < 0.001), and in women (P-trend < 0.001, P-nonlinearity < 0.001). Compared with the minimal category of alcohol consumption, light (RR: 0.83; 95% CI: 0.73, 0.95; P = 0.005) and moderate (RR: 0.74; 95% CI: 0.67, 0.82; P < 0.001) alcohol consumption was associated with a lower risk of T2D. However, heavy alcohol consumption had little or no effect on subsequent T2D risk. Furthermore, the summary RR ratio (RRR; male to female) of the comparison between moderate alcohol consumption and the minimal alcohol categories for T2D was significantly higher, and the pooled RRR (current smoker to never smoker) of light alcohol consumption was significantly reduced. Light and moderate alcohol consumption was associated with a lower risk of T2D, whereas heavy alcohol consumption was not related to the risk of T2D. © 2016 American Society for Nutrition.

Benefits of Alcohol on Arsenic Toxicity in Rats

PubMed Central

Dutta, Shubha Ranjan; Passi, Deepak; Bharti, Jaya

2017-01-01

Introduction It has been demonstrated earlier that exposure to ethanol and/or arsenic compounds (such as sodium arsenite) produces toxic effects as shown by both in vitro and in vivo experiments. Chronic exposure of humans to arsenic through drinking water, pesticides or consumption of alcoholic beverages has produced major health problem and concern in recent years. Water being one of the main ingredients for alcohol formation (beer fermentation process) can lead to contamination with arsenic. Thus, people consuming such alcohol are getting continuously exposed to arsenic compounds as well along with alcohol. Aim The present study was undertaken to investigate the effect of alcohol co-administration on arsenic induced changes in carbohydrate metabolic status in adult male albino rats. Materials and Methods Adult male albino rats of Wistar strain (weighing~100g) were divided into three groups (n=8 rats/group) including Control or vehicle treated (C), Arsenic treated (As) and Arsenic treated alcohol co-exposed (As+Alc). Treatment with Sodium-arsenite included intra-peritoneal injection consecutively for 14 days at a dose of 5.55 mg/kg (equivalent to 35% of LD50) per day. Absolute alcohol (15% v/v) was fed at a dose of 0.5 ml/100 g body weight per day for five consecutive days from start of the treatment schedule. Distilled water (D/W) was used as vehicle. Blood Glucose (BG) level, levels of glycogen, Pyruvic Acid (PA), Free Amino Acid Nitrogen (FAAN), total protein, Glutamate Oxalate transaminase (GOT) and Glutamate Pyruvate Transaminase (GPT) activity, and glucose-6-phosphatase (G6Pase) activity were measured in tissues including liver, kidney and muscle. Results Treatment with arsenic decreased the levels of BG, liver glycogen and PA, tissue protein and G6Pase activity, GOT activity in liver and muscle, and increased free amino acid content in kidney and muscle, GPT activity in liver and kidney. Alcohol administration to rats co-exposed to arsenic treatment reversed these changes. Conclusion Thus, it is suggested that combined administration of alcohol with arsenic can result in the suppression of the down-regulating action of arsenic on glucose homeostasis as evidenced by its hypoglycaemic effect and increased gluconeogenesis and transamination in liver. PMID:28273963

Benefits of Alcohol on Arsenic Toxicity in Rats.

PubMed

Singh, Purnima; Dutta, Shubha Ranjan; Passi, Deepak; Bharti, Jaya

2017-01-01

It has been demonstrated earlier that exposure to ethanol and/or arsenic compounds (such as sodium arsenite) produces toxic effects as shown by both in vitro and in vivo experiments. Chronic exposure of humans to arsenic through drinking water, pesticides or consumption of alcoholic beverages has produced major health problem and concern in recent years. Water being one of the main ingredients for alcohol formation (beer fermentation process) can lead to contamination with arsenic. Thus, people consuming such alcohol are getting continuously exposed to arsenic compounds as well along with alcohol. The present study was undertaken to investigate the effect of alcohol co-administration on arsenic induced changes in carbohydrate metabolic status in adult male albino rats. Adult male albino rats of Wistar strain (weighing~100g) were divided into three groups (n=8 rats/group) including Control or vehicle treated (C), Arsenic treated (As) and Arsenic treated alcohol co-exposed (As+Alc). Treatment with Sodium-arsenite included intra-peritoneal injection consecutively for 14 days at a dose of 5.55 mg/kg (equivalent to 35% of LD50) per day. Absolute alcohol (15% v/v) was fed at a dose of 0.5 ml/100 g body weight per day for five consecutive days from start of the treatment schedule. Distilled water (D/W) was used as vehicle. Blood Glucose (BG) level, levels of glycogen, Pyruvic Acid (PA), Free Amino Acid Nitrogen (FAAN), total protein, Glutamate Oxalate transaminase (GOT) and Glutamate Pyruvate Transaminase (GPT) activity, and glucose-6-phosphatase (G6Pase) activity were measured in tissues including liver, kidney and muscle. Treatment with arsenic decreased the levels of BG, liver glycogen and PA, tissue protein and G6Pase activity, GOT activity in liver and muscle, and increased free amino acid content in kidney and muscle, GPT activity in liver and kidney. Alcohol administration to rats co-exposed to arsenic treatment reversed these changes. Thus, it is suggested that combined administration of alcohol with arsenic can result in the suppression of the down-regulating action of arsenic on glucose homeostasis as evidenced by its hypoglycaemic effect and increased gluconeogenesis and transamination in liver.

[The functional-morphological characteristics of alcohol-induced pathology as dependent on the nature of the intoxication and its nootropil correction in an experiment].

PubMed

Sidorov, P I; Gromova, L E; Solov'ev, A G; Degteva, G N; Leont'ev, V Ia; Savastenko, A E

2000-01-01

The response of hematological system, carbohydrate metabolism and pathomorphologic alterations in the viscera were studied for four weeks on the model of chronic alcoholization in conditions of hydrolytic alcohol production. It is shown that maximal deviations of all the parameters in white conventional rats occur after receiving a combined ethanol dose in inhalation of a mixture of methanol and furfurol vapour. Less manifest pathology was revealed in simultaneous introduction of nootropil solution. Thus, functional-morphologic changes in alcoholic intoxication in unfavourable environment are reversible in purposeful application of drugs with neurometabolic effect.

Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

USDA-ARS?s Scientific Manuscript database

Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial.

PubMed

Beraha, Esther M; Salemink, Elske; Goudriaan, Anna E; Bakker, Abraham; de Jong, David; Smits, Natasha; Zwart, Jan Willem; Geest, Dick van; Bodewits, Pieter; Schiphof, Tom; Defourny, Harma; van Tricht, Mirjam; van den Brink, Wim; Wiers, Reinout W

2016-12-01

Previous randomised placebo-controlled trials with low-to-medium doses of baclofen (30-60mg) showed inconsistent results, but case studies suggested a dose-response effect and positive outcomes in patients on high doses of baclofen (up to 270mg). Its prescription was temporary permitted for the treatment of alcohol dependence (AD) in France, and baclofen is now widely prescribed. Recently, a small RCT found a strong effect of a mean dose of 180mg baclofen. In the present study the efficacy and safety of high doses of baclofen was examined in a multicentre, double-blind, placebo-controlled trial. 151 patients were randomly assigned to either six weeks titration and ten weeks high-dose baclofen (N=58; up to 150mg), low-dose baclofen (N=31; 30mg), or placebo (N=62). The primary outcome measure was time to first relapse. Nine of the 58 patients (15.5%) in the high-dose group reached 150mg and the mean baclofen dose in this group was 93.6mg (SD=40.3). No differences between the survival distributions for the three groups were found in the time to first relapse during the ten-weeks high-dose phase (χ 2 =0.41; p=0.813) or the 16-weeks complete medication period (χ 2 =0.04; p=0.982). There were frequent dose-related adverse events in terms of fatigue, sleepiness, and dry mouth. One medication related serious adverse event occurred in the high-dose baclofen group. Neither low nor high doses of baclofen were effective in the treatment of AD. Adverse events were frequent, although generally mild and transient. Therefore, large-scale prescription of baclofen for the treatment of AD seems premature and should be reconsidered. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Acute Immunomodulatory Effects of Binge Alcohol Ingestion

PubMed Central

Afshar, Majid; Richards, Stephanie; Mann, Dean; Cross, Alan; Smith, Gordon B.; Netzer, Giora; Kovacs, Elizabeth; Hasday, Jeffrey

2014-01-01

BACKGROUND Blood alcohol is present in a third of trauma patients and has been associated with organ dysfunction. In both human studies and in animal models, it is clear that alcohol intoxication exerts immunomodulatory effects several hours to days after exposure, when blood alcohol is no longer detectable. The early immunomodulatory effects of alcohol while blood alcohol is still elevated are not well understood. METHODS Human volunteers achieved binge alcohol intoxication after high-dose alcohol consumption. Blood was collected for analysis prior to alcohol ingestion, and 20 min, 2 h, and 5 h after alcohol ingestion. Flow cytometry was performed on isolated peripheral blood mononuclear cells, and cytokine generation in whole blood was measured by enzyme-linked immunosorbent assay (ELISA) after 24-h stimulation with lipopolysaccharide (LPS) and phytohemagglutinin-M (PHA) stimulation. RESULTS An early pro-inflammatory state was evident at 20 min when blood alcohol levels were ~130 mg/dL, which was characterized by an increase in total circulating leukocytes, monocytes, and natural killer cells. During this time, a transient increase in LPS-induced tumor necrosis factor (TNF)-α levels and enhanced LPS sensitivity occurred. At 2 and 5 h post-alcohol binge, an anti-inflammatory state was shown with reduced numbers of circulating monocytes and natural killer cells, attenuated LPS-induced interleukin (IL)-1β levels, and a trend toward increased interleukin (IL)-10 levels. CONCLUSIONS A single episode of binge alcohol intoxication exerted effects on the immune system that caused an early and transient pro-inflammatory state followed by an anti-inflammatory state. PMID:25572859

Human alcohol-related neuropathology

PubMed Central

Kril, Jillian J.

2015-01-01

Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions. PMID:24370929

Single- and dual-task performance during on-the-road driving at a low and moderate dose of alcohol: A comparison between young novice and more experienced drivers.

PubMed

Jongen, Stefan; van der Sluiszen, Nick N J J M; Brown, Dennis; Vuurman, Eric F P M

2018-05-01

Driving experience and alcohol are two factors associated with a higher risk of crash involvement in young novice drivers. Driving a car is a complex task involving multiple tasks leading to dividing attention. The aim of this study was to compare the single and combined effects of a low and moderate dose of alcohol on single- and dual-task performance between young novice and more experienced young drivers during actual driving. Nine healthy novice drivers were compared with 9 more experienced drivers in a three-way, placebo-controlled, cross-over study design. Driving performance was measured in actual traffic, with standard deviation of lateral position as the primary outcome variable. Secondary task performance was measured with an auditory word learning test during driving. Results showed that standard deviation of lateral position increased dose-dependently at a blood alcohol concentration (BAC) of 0.2 and 0.5 g/L in both novice and experienced drivers. Secondary task performance was impaired in both groups at a BAC of 0.5 g/L. Furthermore, it was found that driving performance in novice drivers was already impaired at a BAC of 0.2 g/L during dual-task performance. The findings suggest that young inexperienced drivers are especially vulnerable to increased mental load while under the influence of alcohol. © 2018 The Authors Human Psychopharmacology: Clinical and Experimental Published by John Wiley & Sons Ltd.

Drivers who self-estimate lower blood alcohol concentrations are riskier drivers after drinking.

PubMed

Laude, Jennifer R; Fillmore, Mark T

2016-04-01

Alcohol increases the tendency for risky driving in some individuals but not others. Little is known about the factors underlying this individual difference. Studies find that those who underestimate their blood alcohol concentration (BAC) following a dose of alcohol tend to be more impulsive and report greater willingness to drive after drinking than those who estimate their BACs to be greater than their actual BAC. BAC underestimation could contribute to risky driving behavior following alcohol as such drivers might perceive little impairment in their driving ability and thus no need for caution. This study was designed to test the relationship between drivers' BAC estimations following a dose of alcohol or a placebo and the degree of risky driving they displayed during a simulated driving test. Forty adult drivers performed a simulated driving test and estimated their blood alcohol concentration after receiving a dose of alcohol (0.65 g/kg for men and 0.56 g/kg for women) or a placebo. Alcohol increased risk-taking and impaired driving skill. Those who estimated their BAC to be lower were the riskiest drivers following both alcohol and placebo. The tendency to estimate lower BACs could support a series of high-risk decisions, regardless of one's actual BAC. This could include the decision to drive after drinking.

Responsibility Study: Main Illicit Psychoactive Substances Among Car Drivers Involved in Fatal Road Crashes

PubMed Central

Gadegbeku, Blandine; Amoros, Emmanuelle; Laumon, Bernard

2011-01-01

In 1999, in France, before considering modifications in drug legislation, the government requested a study of the effect of illicit drugs on the risk of road crashes. It implemented a systematic screening of illicit drugs for all drivers involved in fatal crashes between October 2001 and September 2003. Within the European DRUID project, the study was restricted to car drivers. The project reported here is a responsibility analysis and, as such, it belongs to the framework of case-control studies; the outcome of interest is “being responsible for a fatal crash”. It was assessed with a method adapted from Robertson and Drummer. Cases are the 4,946 car drivers who are responsible for the crash; controls are the 1,986 car drivers selected from the non-responsible car drivers, in a way that makes the control group similar to the general driving population. The effect of cannabis on fatal crash responsibility is significant after adjustment for age, sex and alcohol: adjusted odds ratio is 1.89 [1.43–2.51]. The dose-response effect is significant (p=0.0001). For alcohol (≥0.1 g/l), the adjusted odds ratio for responsibility is 8.39 [6.95–10.11]. No interaction was found between alcohol and cannabis. For amphetamine, cocaine and opiates, adjusted odds ratios were not significantly different from 1. However the statistical power is low. The study finds similar odds ratios for alcohol as previously published. For cannabis, the significant odds ratio together with the significant dose-response effect indicates a causal relationship between cannabis and road crashes. A multiplicative effect between cannabis and alcohol was noted. PMID:22105404

Women's Social Behavior when Meeting New Men: The Influence of Alcohol and Childhood Sexual Abuse

ERIC Educational Resources Information Center

Parks, Kathleen A.; Hequembourg, Amy L.; Dearing, Ronda L.

2008-01-01

Heavy alcohol consumption (Testa & Parks, 1996) and childhood sexual abuse (CSA; Messman-Moore & Long, 2003) have been associated with adult sexual victimization. We examined the social behavior of 42 women under two alcohol conditions (high dose and low dose) in a bar laboratory. Women were videotaped interacting with a man they had just met.…

Baclofen blocks yohimbine-induced increases in ethanol-reinforced responding in rats.

PubMed

Williams, Keith L; Nickel, Melissa M; Bielak, Justin T

2016-05-01

Chronic or repeated stress increases alcohol consumption. The GABA-B agonist baclofen decreases alcohol consumption and may be most effective for individuals with comorbid anxiety/stress disorders. The present study sought to determine if baclofen blocks stress-induced increases in ethanol self-administration as modeled by repeated yohimbine injections in rats. Rats were trained to respond for 15% w/v ethanol in operant chambers using a method that applies neither water deprivation nor saccharin/sucrose fading. Following training, the rats received 6 injections of 1.25mg/kg yohimbine were given immediately prior to the operant sessions during a 2-week time period. Subsequently, some rats were pair-matched to receive either 1.25mg/kg yohimbine or saline in the presence of 0.3, 1, and 3mg/kg baclofen prior to sessions. Acquisition of ethanol self-administration was poor. Pretreatment with yohimbine consistently increased responding across repeated injections. Yohimbine's effect on ethanol intake unexpectedly diverged from the effect on responding as the rats failed to consume all reinforcers earned. Smaller doses of baclofen paired with saline injections had no effect on ethanol responding; only 3mg/kg baclofen reduced ethanol self-administration. The smallest baclofen dose of 0.3mg/kg failed to block the yohimbine-induced increase in self-administration. The large baclofen dose of 3mg/kg continued to suppress ethanol self-administration when given with yohimbine. Baclofen 1mg/kg blocked the effect of yohimbine even though it had no effect when given in the absence of yohimbine. Exposure to high ethanol concentrations may induce self-administration only in certain conditions. The dissociation between responding and intake suggests that repeated yohimbine injections may initiate other behavioral or physiological mechanisms that confound its effects as a pharmacological stressor. Furthermore, an optimal baclofen dose range may specifically protect against stress-induced alcohol self-administration, highlighting a specific contribution of GABA-B receptors and a potential therapeutic efficacy of GABA-B agonists at a non-sedating dose. Copyright © 2016 Elsevier Inc. All rights reserved.

Differentiating the contribution of pharmacological from alcohol expectancy effects to changes in subjective response and priming over successive drinks.

PubMed

Rose, Abigail K; Hobbs, Malcolm; Drummond, Colin

2013-04-01

Alcohol consumption can prime motivation to continue drinking and may contribute to excessive drinking. Most alcohol administration research assesses the effect of a single alcohol dose on outcome measures; however, this differs from typical drinking occasions in which several drinks are consumed over time. This research tracks priming measures (alcohol urge, latency to first sip, and consumption time) and subjective effects (intoxication, stimulation, and sedation) across consumption of 5 drinks, over a period of 2.5 hours. Alcohol, placebo, and no-alcohol (i.e., soft drink) conditions are compared with isolate the effects of alcohol expectancies and differentiate these from alcohol's pharmacological effects. Alcohol urge and subjective state were measured before and after an initial drink was consumed (preload: alcohol, placebo, or no-alcohol). Four additional drinking phases followed whereby participants had access to 2 drinks (alcohol/no-alcohol, or placebo/no-alcohol). Experimental priming (urge, latency to first sip, consumption time) and subjective effect (intoxication, stimulation, and sedation) outcomes were recorded after each drink. The pattern of alcohol urge following placebo drinks differed compared with alcohol and no-alcohol consumption, Fs(1, 90) > 4.10, ps < 0.003. There was a linear decrease in urge in the no-alcohol condition, while in the alcohol condition urge increased after the first few drinks before decreasing. Urge ratings showed the opposite pattern in the placebo condition (a decrease followed by an increase). Alcohol produced the highest ratings of lightheadedness, F(5, 440) = 2.8, p < 0.02, but both alcohol and placebo produced increased sedated feelings, Fs ≥ 19.05, ps ≤ 0.001. After placebo, urge was positively related to liking and enjoying the "alcoholic" drinks and feeling more stimulated (rs ≥ 0.31, ps ≤ 0.01). In social drinkers, different factors may affect priming during different stages of a drinking episode. For example, the pharmacological effects of alcohol appear involved in priming during the initial stages of drinking. When alcohol expectancies are activated, blocking access to alcohol can increase urge, supporting Tiffany's cognitive processing model of craving. Copyright © 2012 by the Research Society on Alcoholism.

Antimicrobial properties and mechanism of volatile isoamyl acetate, a main flavour component of Japanese sake (Ginjo-shu).

PubMed

Ando, H; Kurata, A; Kishimoto, N

2015-04-01

To evaluate the antimicrobial properties of the main Ginjo-flavour components of sake, volatile isoamyl acetate and isoamyl alcohol. Volatile isoamyl acetate and isoamyl alcohol both inhibited growth of the five yeast and 10 bacterial test strains. The minimum inhibitory dose and minimum bactericidal (fungicidal) dose of isoamyl acetate were higher than those of isoamyl alcohol. Escherichia coli and Acetobacter aceti were markedly sensitive to isoamyl acetate and isoamyl alcohol. In E. coli exposed to isoamyl acetate for 5 h, changes in expression were noted in proteins involved in sugar metabolism (MalE, MglB, TalB and PtsI), tricarboxylic acid cycle (AceA, Pfl and AcnB) and protein synthesis (EF-Tu, EF-G, and GlyS). Expression of acid and alcohol stress-response proteins was altered in E. coli exposed to isoamyl acetate. Esterase activity was detected in E. coli, suggesting that isoamyl acetate was hydrolyzed to acetic acid and isoamyl alcohol. Acetic acid and isoamyl alcohol damaged E. coli cell membranes and inactivated membrane proteins, impairing respiration. Volatile isoamyl acetate and isoamyl alcohol were effective in inactivating various micro-organisms, and antimicrobial mechanism of volatile isoamyl acetate against E. coli was clarified based on proteome analysis. To the best of our knowledge, this is the first report to examine the antimicrobial mechanism of volatile organic compound using proteome analysis combining two-dimensional difference gel electrophoresis with peptide mass fingerprinting. © 2015 The Society for Applied Microbiology.

Covert effects of "one drink" of alcohol on brain processes related to car driving: an event-related potential study.

PubMed

Ebe, Kazutoshi; Itoh, Kosuke; Kwee, Ingrid L; Nakada, Tsutomu

2015-04-23

The effects of a low dose of alcohol on car driving remain controversial. To address this issue, event-related potentials were recorded while subjects performed a simple car-following task in a driving simulator before and after consuming either "one drink" of beer (representing one standard alcoholic beverage containing 14 g of alcohol) or mineral water (control condition). Subjects who had consumed the determined amount of alcohol demonstrated no detectable outward behavioral signs of intoxication while performing the driving task, an observation in agreement with previous findings. However, the parietal P3 elicited by the brake lights of the preceding car was significantly reduced in amplitude, approximately 50% that observed under the control condition, likely indicating alteration of the neural processing of visual information critical for safe driving. The finding suggests that alcohol begins to affect neural processes for driving even at quantities too low to modify behavior. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Increased Behavioral Economic Demand and Craving for Alcohol following a Laboratory Alcohol Challenge

PubMed Central

Amlung, Michael; McCarty, Kayleigh N.; Morris, David H.; Tsai, Chia-Lin; McCarthy, Denis M.

2015-01-01

Background and aims Although increases in subjective alcohol craving have been observed following moderate doses of alcohol (e.g., priming effects), the effects of alcohol consumption on behavioral economic demand for alcohol are largely unstudied. This study examined the effects of alcohol intoxication on alcohol demand and craving. Design A between-subjects design in which participants were randomly assigned to either an alcohol (n = 31), placebo (n = 29) or control (n = 25) condition. Setting A laboratory setting at the University of Missouri, USA. Participants Eighty-five young adult moderate drinkers were recruited from the University of Missouri and surrounding community. Measurements Change in demand for alcohol across time was measured using three single items: alcohol consumption at no cost (i.e., intensity), maximum price paid for a single drink (i.e., breakpoint), and total amount spent on alcohol (i.e., Omax). Alcohol demand at baseline was also assessed using an alcohol purchase task (APT). Craving was assessed using a single visual analog scale item. Findings In the alcohol group compared with the combined non-alcohol groups, intensity, breakpoint, and craving increased from baseline to the ascending limb and decreased thereafter (ps < 0.05; Omax p = 0.06). Change in craving following alcohol consumption was significantly associated with change in each of the demand indices (ps < 0.0001). Finally, the demand single items were associated with corresponding indices from the APT (ps < 0.01). Conclusions Alcohol demand increases following intoxication, in terms of both the maximum amount people are willing to pay for one drink and the number of drinks people would consume if drinks were free. Behavioral economic measures of alcohol value can complement subjective craving as measures of moment-to-moment fluctuations in drinking motivation following intoxication. PMID:25732875

Roles of the locus coeruleus and adrenergic receptors in brain-mediated hypothalamic-pituitary-adrenal axis responses to intracerebroventricular alcohol.

PubMed

Selvage, Dan

2012-06-01

Alcohol activates the hypothalamic-pituitary-adrenal (HPA) axis through its actions in both the periphery and the central nervous system (CNS). The studies presented here were designed to test the CNS-specific noradrenergic mechanisms by which alcohol stimulates HPA activity in the male rat. We used an experimental paradigm in which a small, nontoxic amount (5 μl) of alcohol was slowly microinfused intracerebroventricularly (icv). Alcohol was administered icv to animals with lesions of the locus coeruleus (LC) or in animals pretreated with α- or β-adrenergic receptor antagonists. Hormonal HPA activation was determined by measuring secretion of the pituitary stress hormone adrenocorticotropin (ACTH). Neuronal activation was determined by quantification of the expression of the transcription factor c-fos (Fos). As expected, icv alcohol stimulated ACTH secretion from the pituitary and Fos expression in the paraventricular nucleus of the hypothalamus (PVN). Bilateral electrolytic LC lesions blocked the ability of icv alcohol to stimulate ACTH secretion. Pretreatment with icv propranolol increased basal ACTH secretion levels, but icv alcohol did not increase this effect. Propranolol also blunted icv alcohol-induced PVN Fos expression. A low dose of phenoxybenzamine, an α-adrenergic receptor antagonist, did not affect the ability of icv alcohol to stimulate ACTH release. However, a higher dose of the drug was able to block the ACTH response to icv alcohol. Despite this, phenoxybenzamine did not inhibit alcohol-induced Fos expression. Icv pretreatment with corynanthine, a selective α-1 adrenergic receptor antagonist, modestly raised basal ACTH levels and blocked the icv alcohol-induced secretion of this hormone. These results indicate that the LC and norepinephrine play important roles in HPA activation caused by icv alcohol administration, but that the specific adrenergic receptor subtypes involved in this phenomenon still need to be identified. Copyright © 2012 by the Research Society on Alcoholism.

Acute effects of alcohol on memory: impact of emotional context and serial position.

PubMed

Brown, Jennie; Brignell, Catherine M; Dhiman, Sharinjeet K; Curran, H Valerie; Kamboj, Sunjeev K

2010-03-01

Although the amnestic effects of alcohol in humans are well known, its effects on emotional memory are unclear. In this study, using a randomized double-blind placebo-controlled design, we examine narrative emotional episodic memory in healthy human female volunteers (n=32) who received either a single dose of alcohol (0.6g/kg), or a placebo and then viewed neutral story elements presented in either a neutral or emotional context. Memory was tested for gist and detail of the neutral elements 3days later in a surprise recognition test. Since alcohol modulates GABAergic neurotransmission and may exert its effects on emotion through the limbic system, we predicted that acute alcohol treatment would reduce the expected emotional memory-advantage for gist, leaving detail memory relatively unaffected. Furthermore, given previous findings showing that 'primacy' memory is enhanced by physiological arousal, we predicted that reduced arousal produced by alcohol would have the opposite effect and impair primacy memory relative to the middle or 'recency' sections of the narrative. Emotional arousal was expected to oppose this effect, so impaired primacy memory following alcohol was only expected in the neutral version of the narrative. Although there was a main effect of story phase (though not of story version), contrary to expectations, alcohol impaired primacy memory for emotionally encoded neutral material. The results suggest that under certain circumstances emotional context or physiological arousal make memories labile and susceptible to disruption through pharmacological manipulation during encoding. 2009 Elsevier Inc. All rights reserved.

Fetal Alcohol Spectrum Disorders.

PubMed

Williams, Janet F; Smith, Vincent C

2015-11-01

Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus. Copyright © 2015 by the American Academy of Pediatrics.

Fetal and infantile alcohol-mediated associative learning in the rat.

PubMed

Abate, P; Spear And, N E; Molina, J C

2001-07-01

Infant rats express conditioned responses to an odor experienced prenatally as a chemosensory cue associated with moderate alcohol intoxication. This study examined postnatal intake of a chemosensory cue (cineole) that had been paired with alcohol's unconditioned effects. It also tested the interaction between prenatal association and postnatal conditioning with cineole and alcohol. Pregnant female rats intubated with cineole were given ethanol (EtOH).25 or 4.0 hr later. Other groups received only water or water paired with ethanol. During postnatal day 15 (PD15), infant consumption of cineole solution was assessed. After the cineole drinking test, pups were intubated with EtOH or water to assess infant conditioning. On PD16, all pups were tested for mouthing to milk alone or to a milk-cineole solution. Statistical analysis confirmed fetal associative conditioning attributable to the unconditioned effects of prenatal alcohol. Fetuses given explicit pairings of cineole and alcohol ingested less cineole on PD15 than control fetuses given a 4-hr interval between cineole and alcohol. On PD16, consumption of cineole was significantly increased by prenatal exposure to cineole. Teratogenic effects of this dose of prenatal alcohol did not affect postnatal associative or nonassociative behavior. Prenatal associative learning can be established through temporal contiguity between fetal chemosensory stimulation and alcohol's unconditioned properties. This associative memory survives to infancy and modulates intake patterns and behavioral reactivity to substances that were prenatally paired with alcohol intoxication.

The efficacy of a low dose combination of topiramate and naltrexone on ethanol reinforcement and consumption in rat models.

PubMed

Moore, Catherine F; Protzuk, Omar A; Johnson, Bankole A; Lynch, Wendy J

2014-01-01

Combined medication approaches, by targeting multiple neurotransmitter systems involved in alcohol use disorders (AUDs), may be more efficacious than single-medication approaches. We examined, in animal models of consumption and reinforcement, the combined effects of naltrexone (an opioid antagonist) and topiramate (a GABA/glutamate modulator), two medications that have shown promise for treating AUDs, hypothesizing that their combination would be more efficacious than either alone. The effects of naltrexone and topiramate on ethanol consumption were examined in alcohol preferring (P) rats (N=10) and in rats from their background strain (Wistar, N=9) using conditions that induce high levels of consumption (24-h, 3-bottle, free-choice procedure). Low doses of each medication (1mg/kg, naltrexone; 10mg/kg, topiramate) were selected in an attempt to maximize their combined efficacy while minimizing potential side-effects. Their effects on ethanol reinforcement were assessed under a progressive-ratio schedule in additional groups of (N=22) P rats. A moderate dose of topiramate (20mg/kg) was also included to verify topiramate's efficacy on its own. In P rats, but not in Wistar rats, the combination effectively and persistently reduced consumption; whereas, neither dose alone was effective. The combination and naltrexone alone were equally effective at reducing ethanol reinforcement; however, with the combination, but not naltrexone alone, this effect was selective for ethanol. All treatments produced a similar decrease in home-cage food consumption. The 20mg/kg dose of topiramate also effectively reduced ethanol consumption and reinforcement. With greater efficacy and fewer side-effects, the combination shows promise as a treatment for AUDs. Copyright © 2013 Elsevier Inc. All rights reserved.

The efficacy of a low dose combination of topiramate and naltrexone on ethanol reinforcement and consumption in rat models

PubMed Central

Moore, Catherine F; Protzuk, Omar A; Johnson, Bankole A; Lynch, Wendy J

2013-01-01

Rationale Combined medication approaches, by targeting multiple neurotransmitter systems involved in alcohol use disorders (AUDs), may be more efficacious than single-medication approaches. Objectives We examined, in animals models of consumption and reinforcement, the combined effects of naltrexone (an opioid antagonist) and topiramate (a GABA/glutamate modulator), two medications that have shown promise for treating AUDs, hypothesizing that their combination would be more efficacious than either alone. Methods The effects of naltrexone and topiramate on ethanol consumption were examined in alcohol preferring (P) rats (N=10) and in rats from their background strain (Wistar, N=9) using conditions that induce high levels of consumption (24-hr, 3-bottle, free-choice procedure). Low doses of each medication (1 mg/kg, naltrexone; 10 mg/kg, topiramate) were selected in an attempt to maximize their combined efficacy while minimizing potential side-effects. Their effects on ethanol reinforcement were assessed under a progressive-ratio schedule in additional groups of (N=22) P rats. A moderate dose of topiramate (20 mg/kg) was also included to verify topiramate’s efficacy on its own. Results In P rats, but not Wistar rats, the combination effectively and persistently reduced consumption; whereas, neither dose alone was effective. The combination and naltrexone alone were equally effective at reducing ethanol reinforcement; however, with the combination, but not naltrexone alone, this effect was selective for ethanol. All treatments produced a similar decrease in home-cage food consumption. The 20 mg/kg dose of topiramate also effectively reduced ethanol consumption and reinforcement. Conclusions With greater efficacy and fewer side-effects, the combination shows promise as a treatment for AUDs. PMID:24252444

A healthy dose of scepticism: four good reasons to think again about protective effects of alcohol on coronary heart disease.

PubMed

Chikritzhs, Tanya; Fillmore, Kaye; Stockwell, Tim

2009-07-01

Alcohol has been implicated in both the popular press and scientific literature as having a protective effect for at least a dozen conditions including coronary heart disease (CHD). Epidemiological evidence for an apparent protective effect of alcohol on CHD is now being challenged on a number of fronts. This paper is a synopsis of those various challenges as they currently stand. The argument that systematic misclassification of ex-drinkers and occasional drinkers to 'abstainer' categories among epidemiological studies might explain apparent protective effects of moderate alcohol consumption on CHD has recently been supported by new meta-analyses and independent research. The influence of uncontrolled or unknown factors on the relationship between alcohol and disease cannot be ruled out. Exclusion of participants on the basis of ill-health severely reduces study sample size and new analyses suggest that doing so might artificially create the appearance of protective effects. The ability of respondents to accurately recall their own alcohol consumption is in serious doubt and very few individuals maintain one single drinking level or style throughout life. The relationship between alcohol and some conditions might be a function of drinking patterns but few studies have addressed the issue. Popular perceptions regarding the strength of evidence for alcohol's protective effect on a growing number of conditions might be misguided. It is time for the wider research, health and medical community to seriously reflect on the quality of current evidence for apparent protective effects of alcohol on human disease.

Pharmacodynamic interactions of a solid formulation of sodium oxybate and ethanol in healthy volunteers

PubMed Central

Pross, Nathalie; Patat, Alain; Vivet, Philippe; Bidaut, Michelle; Fauchoux, Nicolas

2015-01-01

Aim The pharmacologic effects of sodium oxybate (SO) have a number of similarities with those of alcohol. This study evaluated the pharmacodynamic interaction of SMO.IR (a solid immediate release formulation of SO) and alcohol (0.7 (males) or 0.57 (females) g kg–1 alcohol using 40% vodka). Methods In a randomized, double-blind, double-dummy, crossover trial, 24 healthy volunteers received randomly a) 2.25 g SMO.IR and placebo alcohol preparation, b) 2.25 g f SMO.IR and alcohol, c) 2.25 g SMO.IR matching placebo and alcohol and d) 2.25 g of SMO.IR matching placebo and placebo alcohol preparation. Objective and subjective cognitive parameters, adverse events and vital signs were assessed before, 15 and 165 min after treatment administration. Results Alcohol produced the expected cognitive impairment and the expected subjective sedation rapidly after intake (from 15 min). The objective effects of SMO.IR were much less pronounced than those of alcohol. The reverse was observed for subjective complaints, which were related to lesser stimulation and greater sedation. Nevertheless, 165 min after administration this sedation feeling was less with SMO.IR than with alcohol. There was a significant interaction between SMO.IR and alcohol at 15 min (i.e. increase in alertness and stimulation and decrease in sedation). In addition, an isolated mild decrease in digit vigilance accuracy occurred at 165 min post-dose after the combination. The co-administration of SMO.IR and alcohol was safe and well-tolerated. Conclusion SMO.IR and alcohol have distinct adverse effect profiles. The objective effects of SMO.IR are much less marked than those of alcohol. No deleterious interaction was observed. PMID:25782469

Alcohol and aggressive behavior in men--moderating effects of oxytocin receptor gene (OXTR) polymorphisms.

PubMed

Johansson, A; Bergman, H; Corander, J; Waldman, I D; Karrani, N; Salo, B; Jern, P; Algars, M; Sandnabba, K; Santtila, P; Westberg, L

2012-03-01

We explored if the disposition to react with aggression while alcohol intoxicated was moderated by polymorphic variants of the oxytocin receptor gene (OXTR). Twelve OXTR polymorphisms were genotyped in 116 Finnish men [aged 18-30, M = 22.7, standard deviation (SD) = 2.4] who were randomly assigned to an alcohol condition in which they received an alcohol dose of 0.7 g pure ethanol/kg body weight or a placebo condition. Aggressive behavior was measured using a laboratory paradigm in which it was operationalized as the level of aversive noise administered to a fictive opponent. No main effects of the polymorphisms on aggressive behavior were found after controlling for multiple testing. The interactive effects between alcohol and two of the OXTR polymorphisms (rs4564970 and rs1488467) on aggressive behavior were nominally significant and remained significant for the rs4564970 when controlled for multiple tests. To the best of our knowledge, this is the first experimental study suggesting interactive effects of specific genetic variants and alcohol on aggressive behavior in humans. © 2011 The Authors. Genes, Brain and Behavior © 2011 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Substance use and adherence among people living with HIV/AIDS receiving cART in Latin America

PubMed Central

De Boni, Raquel B.; Shepherd, Bryan E.; Grinsztejn, Beatriz; Cesar, Carina; Cortés, Claudia; Padgett, Denis; Gotuzzo, Eduardo; Belaunzarán-Zamudio, Pablo F.; Rebeiro, Peter F.; Duda, Stephany N.; McGowan, Catherine C.

2016-01-01

This cross-sectional study describes substance use prevalence and its association with cART adherence among 3343 individuals receiving care at HIV clinics in Argentina, Brazil, Chile, Honduras, Mexico, and Peru. A rapid screening tool evaluated self-reported 7-day recall of alcohol, marijuana, cocaine, heroin, and methamphetamine use, and missed cART doses. Overall, 29.3% individuals reported having ≥ 1 alcoholic drinks, 5.0% reported any illicit drug use and 17.0% reported missed cART doses. In the logistic regression model, compared to no substance use, alcohol use (adjusted odds ratio (AOR)=2.46, 95% confidence interval (CI): 1.99–3.05), illicit drug use (AOR=3.57, 95% CI: 2.02–6.30), and using both alcohol and illicit drugs (AOR=4.98, 95% CI: 3.19–7.79) were associated with missed cART doses. The associations between substance use and likelihood of missing cART doses point to the need of targeting alcohol and illicit drug use to improve adherence among people living with HIV in Latin America. PMID:27091028

A Role for Prefrontal Cortical NMDA Receptors in Murine Alcohol-Heightened Aggression.

PubMed

Newman, Emily L; Terunuma, Miho; Wang, Tiffany L; Hewage, Nishani; Bicakci, Matthew B; Moss, Stephen J; DeBold, Joseph F; Miczek, Klaus A

2018-05-01

Alcohol is associated with nearly half of all violent crimes committed in the United States; yet, a potential neural basis for this type of pathological aggression remains elusive. Alcohol may act on N-methyl-d-aspartate receptors (NMDARs) within cortical circuits to impede processing and to promote aggression. Here, male mice were characterized as alcohol-heightened (AHAs) or alcohol non-heightened aggressors (ANAs) during resident-intruder confrontations after self-administering 1.0 g/kg alcohol (6% w/v) or water. Alcohol produced a pathological-like pattern of aggression in AHAs; these mice shifted their bites to more vulnerable locations on the body of a submissive animal, including the anterior back and ventrum after consuming alcohol. In addition, through immunoblotting, we found that AHAs overexpressed the NMDAR GluN2D subunit in the prefrontal cortex (PFC) as compared to ANAs while the two phenotypes expressed similar levels of GluN1, GluN2A and GluN2B. After identifying several behavioral and molecular characteristics that distinguish AHAs from ANAs, we tested additional mice for their aggression following preferential antagonism of GluN2D-containing NMDARs. In these experiments, groups of AHAs and ANAs self-administered 1.0 g/kg alcohol (6% w/v) or water before receiving intraperitoneal (i.p.) doses of ketamine or memantine, or infusions of memantine directly into the prelimbic (PLmPFC) or infralimbic medial PFC (ILmPFC). Moderate doses of IP ketamine, IP memantine, or intra-PLmPFC memantine increased aggression in AHAs, but only in the absence of alcohol. Prior alcohol intake blocked the pro-aggressive effects of ketamine or memantine. In contrast, only memantine, administered systemically or intra-PLmPFC, interacted with prior alcohol intake to escalate aggression in ANAs. Intra-ILmPFC memantine had no effect on aggression in either AHAs or ANAs. In sum, this work illustrates a potential role of GluN2D-containing NMDARs in the PLmPFC in alcohol-heightened aggression. GluN2D-containing NMDARs are highly expressed on cortical parvalbumin-containing interneurons, suggesting that, in a subset of individuals, alcohol may functionally alter signal integration within cortical microcircuits to dysregulate threat reactivity and promote aggression. This work suggests that targeting GluN2D-NMDARs may be of use in reducing the impact of alcohol-related violence in the human population.

Paracetamol, alcohol and the liver

PubMed Central

Prescott, Laurie F

2000-01-01

It is claimed that chronic alcoholics are at increased risk of paracetamol (acetaminophen) hepatotoxicity not only following overdosage but also with its therapeutic use. Increased susceptibility is supposed to be due to induction of liver microsomal enzymes by ethanol with increased formation of the toxic metabolite of paracetamol. However, the clinical evidence in support of these claims is anecdotal and the same liver damage after overdosage occurs in patients who are not chronic alcoholics. Many alcoholic patients reported to have liver damage after taking paracetamol with ‘therapeutic intent’ had clearly taken substantial overdoses. No proper clinical studies have been carried out to investigate the alleged paracetamol–alcohol interaction and acute liver damage has never been produced by therapeutic doses of paracetamol given as a challenge to a chronic alcoholic. The paracetamol–alcohol interaction is complex; acute and chronic ethanol have opposite effects. In animals, chronic ethanol causes induction of hepatic microsomal enzymes and increases paracetamol hepatotoxicity as expected (ethanol primarily induces CYP2E1 and this isoform is important in the oxidative metabolism of paracetamol). However, in man, chronic alcohol ingestion causes only modest (about twofold) and short-lived induction of CYP2E1, and there is no corresponding increase (as claimed) in the toxic metabolic activation of paracetamol. The paracetamol–ethanol interaction is not specific for any one isoform of cytochrome P450, and it seems that isoenzymes other than CYP2E1 are primarily responsible for the oxidative metabolism of paracetamol in man. Acute ethanol inhibits the microsomal oxidation of paracetamol both in animals and man. This protects against liver damage in animals and there is evidence that it also does so in man. The protective effect disappears when ethanol is eliminated and the relative timing of ethanol and paracetamol intake is critical. In many of the reports where it is alleged that paracetamol hepatotoxicity was enhanced in chronic alcoholics, the reverse should have been the case because alcohol was actually taken at the same time as the paracetamol. Chronic alcoholics are likely to be most vulnerable to the toxic effects of paracetamol during the first few days of withdrawal but maximum therapeutic doses given at this time have no adverse effect on liver function tests. Although the possibility remains that chronic consumption of alcohol does increase the risk of paracetamol hepatotoxicity in man (perhaps by impairing glutathione synthesis), there is insufficient evidence to support the alleged major toxic interaction. It is astonishing that clinicians and others have unquestion-ingly accepted this supposed interaction in man for so long with such scant regard for scientific objectivity. PMID:10759684

Neurological and neuropsychological effects of low and moderate prenatal alcohol exposure.

PubMed

Comasco, E; Rangmar, J; Eriksson, U J; Oreland, L

2018-01-01

Several explanations for the diverse results in research on foetal alcohol spectrum disorders or alcohol-related neurodevelopmental disorder might be at hand: timing, amount and patterns of alcohol exposure, as well as complex epigenetic responses. The genetic background of the offspring and its interaction with other prenatal and post-natal environmental cues are likely also of importance. In the present report, key findings about the possible effects of low and moderate doses of maternal alcohol intake on the neuropsychological development of the offspring are reviewed and plausible mechanisms discussed. Special focus is put on the serotonergic system within developmental and gene-environment frameworks. The review also suggests guidelines for future studies and also summarizes some of to-be-answered questions of relevance to clinical practice. Contradictory findings and paucity of studies on the effects of exposure to low alcohol levels during foetal life for the offspring's neuropsychological development call for large prospective studies, as well as for studies including neuroimaging and multi-omics analyses to dissect the neurobiological underpinnings of alcohol exposure-related phenotypes and to identify biomarkers. Finally, it remains to be investigated whether any safe threshold of alcohol drinking during pregnancy can be identified. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Ivermectin reduces alcohol intake and preference in mice

PubMed Central

Yardley, Megan; Wyatt, Letisha; Khoja, Sheraz; Asatryan, Liana; Ramaker, Marcia J.; Finn, Deborah A.; Alkana, Ronald L.; Huynh, Nhat; Louie, Stan G.; Petasis, Nicos A.; Bortolato, Marco; Davies, Daryl L.

2012-01-01

The high rate of therapeutic failure in the management of alcohol use disorders (AUDs) underscores the urgent need for novel and effective strategies that can deter ethanol consumption. Recent findings from our group showed that ivermectin (IVM), a broad-spectrum anthelmintic with high tolerability and optimal safety profile in humans and animals, antagonized ethanol-mediated inhibition of P2X4 receptors (P2X4Rs) expressed in Xenopus oocytes. This finding prompted us to hypothesize that IVM may reduce alcohol consumption; thus, in the present study we investigated the effects of this agent on several models of alcohol self-administration in male and female C57BL/6 mice. Overall, IVM (1.25–10 mg/kg, intraperitoneal) significantly reduced 24-h alcohol consumption and intermittent limited access (4-h) binge drinking, and operant alcohol self-administration (1-h). The effects on alcohol intake were dose-dependent with the significant reduction in intake at 9 h after administration corresponding to peak IVM concentrations (Cmax) in the brain. IVM also produced a significant reduction in 24-h saccharin consumption, but did not alter operant sucrose self-administration. Taken together, the findings indicate that IVM reduces alcohol intake across several different models of self-administration and suggest that IVM may be useful in the treatment of AUDs. PMID:22465817

Baclofen for alcohol dependence: Relationships between baclofen and alcohol dosing and the occurrence of major sedation.

PubMed

Rolland, Benjamin; Labreuche, Julien; Duhamel, Alain; Deheul, Sylvie; Gautier, Sophie; Auffret, Marine; Pignon, Baptiste; Valin, Thomas; Bordet, Régis; Cottencin, Olivier

2015-10-01

High-dose baclofen, i.e., 300 mg/d or more, has recently emerged as a strategy for treating alcohol dependence. The impact that the co-exposure of large amounts of alcohol and baclofen has on sedation is unclear. In a prospective cohort of 253 subjects with alcohol dependence, we collected daily alcohol and baclofen doses across the first year of baclofen treatment and the monthly maximum subjective sedation experienced by each patient (0-10 visual analog scale). For each patient-month, we determined the average weekly alcohol consumption (AWAC; standard-drinks/week) and the maximum daily dose of baclofen (DDB; mg/d). The occurrence of an episode of major sedation (EMS) during a patient-month was defined as a sedation score ≥7. The relationship between the EMS occurrence and the concurrent AWAC and DDB was investigated using a generalized estimating equation model. In total, 1528 patient-months were compiled (70 with an EMS). Univariate analyses demonstrated that the rate of patient-month to EMS increased gradually with AWAC (p<0.001), from 0.9% for AWAC=0 to 9.4% for AWAC >35. There was also a significant gradual risk for EMS associated with DDB (<0.001). Multivariate analysis demonstrated a significant interaction between DDB and AWAC on EMS risk (p=0.047). Each 20mg/d increase in DDB was associated with an OR of EMS in AWAC >35 of 1.22 (95%CI, 1.08-1.38) versus 1.11 (95%CI, 0.96-1.29) in AWAC=1-35, and 0.95 (95%CI, 0.76-1.19) in AWAC=0. The level of sedation observed in patients using baclofen for alcohol dependence appears to directly depend on the immediate doses of both the baclofen and the alcohol. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Study I: effects of 0.06% and 0.10% blood alcohol concentration on human postural control.

PubMed

Modig, F; Patel, M; Magnusson, M; Fransson, P A

2012-03-01

Alcohol intoxication causes many accidental falls presented at emergency departments, with the injury severity often related to level of blood alcohol concentration (BAC). One way to evaluate the decline in postural control and the fall risk is to assess standing stability when challenged. The study objective was to comprehensively investigate alcohol-related impairments on postural control and adaptive motor learning at specific BAC levels. Effects of alcohol intoxication at 0.06% and 0.10% BAC were examined with posturography when unperturbed or perturbed by calf vibration. Twenty-five participants (mean age 25.1 years) were investigated standing with either eyes open or closed. Our results revealed several significant findings: (1) stability declined much faster from alcohol intoxication between 0.06% and 0.10% BAC (60-140%) compared with between 0.0% and 0.06% BAC (30%); (2) sustained exposure to repeated balance perturbations augmented the alcohol-related destabilization; (3) there were stronger effects of alcohol intoxication on stability in lateral direction than in anteroposterior direction; and (4) there was a gradual degradation of postural control particularly in lateral direction when the balance perturbations were repeated at 0.06% and 0.10% BAC, indicating adaptation deficits when intoxicated. To summarize, alcohol has profound deteriorating effects on human postural control, which are dose dependent, time dependent and direction specific. The maximal effects of alcohol intoxication on physiological performance might not be evident initially, but may be revealed first when under sustained sensory-motor challenges. Copyright © 2011 Elsevier B.V. All rights reserved.

Low-Dose Naltrexone: A New Therapy Option for Complex Regional Pain Syndrome Type I Patients.

PubMed

Sturn, Kayla M; Collin, Michael

2016-01-01

Naltrexone (an opioid antagonist) has long been used in patients overcoming alcohol and opioid dependency. However, at doses one-tenth of those commonly prescribed for the above conditions, an unexpected effect occurs that aids in alleviating pain. Although there are currently no randomized clinical trials supporting the use of low-dose naltrexone, we present a case study describing the impact of compounding low-dose naltrexone that has dramatically improved the patient's pain symptoms which were refractory to other treatments. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

The effects of crude aqueous and alcohol extracts of Aloe vera on growth and abdominal viscera of suckling rats.

PubMed

Beya, Wabeya; Davidson, Bruce; Erlwanger, Kennedy H

2012-01-01

The gastrointestinal tract of neonates is sensitive to dietary manipulations. When nursing mothers use Aloe vera, their babies are at risk of indirect exposure to Aloe vera via breast feeding or directly as health supplements. The effects of orally administered extracts of Aloe vera in unweaned rats were investigated. Six day old Sprague-Dawley rats were gavaged with aqueous or alcohol extracts of Aloe vera (low dose 50mg. kg⁻¹ or high dose 500mg. kg⁻¹) daily for eight days. All data were expressed as mean ± SD and analyzed by one way ANOVA. Pups receiving high doses of either extract had a significantly higher body mass gain than the group receiving lower dose (p < 0.05). Tibial length was significantly increased in the high dose aqueous extract group (15-26%). The differences in growth could not be attributed to circulating insulin-like growth factor-1 as the levels were not significantly different. The caecum was significantly enlarged in the rats that received the high doses of both extracts. Although, there was no significant difference in the non-fasting plasma concentration of glucose and triglycerides, the hepatic lipid and glycogen content were significantly higher (p < 0.001) for the high dose aqueous extract group. The plasma alanine transaminase was not affected by the treatments, however the high doses of the extracts significantly increased plasma alkaline phosphatase activity. Short term administration of Aloe vera extracts resulted in growth promotion, enhanced hepatic storage of metabolic substrates, increased ALP possibly in relation to bone growth and caused hypertrophy of the caecum of neonatal rats. These effects need to be explored further to enhance animal production and health.

Drivers who self-estimate lower blood alcohol concentrations are riskier drivers after drinking

PubMed Central

Laude, Jennifer R.; Fillmore, Mark T.

2016-01-01

Rationale Alcohol increases the tendency for risky driving in some individuals, but not others. Little is known about the factors underlying this individual difference. Studies find that those who underestimate their blood alcohol concentration (BAC) following a dose of alcohol tend to be more impulsive and report greater willingness to drive after drinking than those who estimate their BACs to be greater than their actual BAC. BAC underestimation could contribute to risky driving behavior following alcohol as such drivers might perceive little impairment in their driving ability and thus no need for caution. Objectives This study was designed to test the relationship between drivers’ BAC estimations following a dose of alcohol or a placebo and the degree of risky driving they displayed during a simulated driving test. Methods Forty adult drivers performed a simulated driving test and estimated their blood alcohol concentration after receiving a dose of alcohol (0.65 g/kg for men; 0.56 g/kg for women) or a placebo. . Results Alcohol increased risk taking and impaired driving skill. Those who estimated their BAC to be lower were the riskiest drivers following both alcohol and placebo. Conclusions The tendency to estimate lower BACs could support a series of high-risk decisions, regardless of one’s actual BAC. This could include the decision to drive after drinking. PMID:26861796

Modulation of alcohol preference by NMDA antagonists in male rats.

PubMed

Lamblin, F; Deuceuninck, D; De Witte, P

1993-11-01

Chronic alcoholization by alcohol inhalation was used to study the properties of magnesium, a non-competitive NMDA receptor antagonist, and CGP 39551, a competitive NMDA receptor antagonist, on behavioural dependence as estimated by the free-choice paradigm [alcohol 10% (v/v) vs. water], on the hypermotility after alcohol withdrawal, and finally on the cortical vascularization. The first experimental group received the drugs per os during the whole alcoholization period. Magnesium (20 mg/kg/day) decreased the alcohol dependence while CGP 39551 (5 and 10 mg/kg/day) increased, in a dose-dependent manner, the dependence to alcohol. A second group of animals received the same drugs at the same dosages, not simultaneously during chronic alcoholization, but immediately after alcoholization in one shot i.p. injection. In this case, rats receiving 5 mg/kg CGP 39551 never showed any dependence towards alcohol, while 10 mg/kg CGP 39551 or 20 mg/kg magnesium prolonged the number of days of alcohol dependence. These results thus indicate the close interaction between NMDA receptor function and dependence for alcohol. Magnesium had no effects on hypermotility, while CGP 39551-treated animals presented a decrease in the hypermotility observed after alcohol withdrawal. Neither drug affected the hypervascularization accompanying the chronic alcoholization.

Acute effects of alcohol on feedback processing and outcome evaluation during risky decision-making: an ERP study.

PubMed

Euser, Anja S; van Meel, Catharina S; Snelleman, Michelle; Franken, Ingmar H A

2011-09-01

Although risky decision-making is one of the hallmarks of alcohol use disorders, relatively little is known about the acute psychopharmacological effects of alcohol on decision-making processes. The present study investigated the acute effects of alcohol on neural mechanisms underlying feedback processing and outcome evaluation during risky decision-making, using event-related brain potentials (ERPs). ERPs elicited by positive and negative feedback were recorded during performance of a modified version of the Balloon Analogue Risk Task in male participants receiving either a moderate dose of alcohol (0.65 g/kg alcohol; n = 32) or a non-alcoholic placebo beverage (n = 32). Overall, there was no significant difference in the mean number of pumps between the alcohol and the placebo condition. However, when analyzing over time, it was found that the alcohol group made more riskier choices at the beginning of the task than the placebo group. ERPs demonstrated that alcohol consumption did not affect early processing of negative feedback, indexed by the feedback-related negativity. By contrast, alcohol-intoxicated individuals showed significantly reduced P300 amplitudes in response to negative feedback as compared to sober controls, suggesting that more elaborate evaluation to losses was significantly diminished. These results suggest that alcohol consumption does not influence the ability to rapidly evaluate feedback valence, but rather the ability to assign sufficient attention to further process motivationally salient outcomes. Blunted P300 amplitudes may reflect poor integration of feedback across trials, particularly adverse ones. Consequently, alcohol may keep people from effectively predicting the probability of future gains and losses based on their reinforcement history.

Low Dose Prenatal Alcohol Exposure Does Not Impair Spatial Learning and Memory in Two Tests in Adult and Aged Rats

PubMed Central

Cullen, Carlie L.; Burne, Thomas H. J.; Lavidis, Nickolas A.; Moritz, Karen M.

2014-01-01

Consumption of alcohol during pregnancy can have detrimental impacts on the developing hippocampus, which can lead to deficits in learning and memory function. Although high levels of alcohol exposure can lead to severe deficits, there is a lack of research examining the effects of low levels of exposure. This study used a rat model to determine if prenatal exposure to chronic low dose ethanol would result in deficits in learning and memory performance and if this was associated with morphological changes within the hippocampus. Sprague Dawley rats were fed a liquid diet containing 6% (vol/vol) ethanol (EtOH) or an isocaloric control diet throughout gestation. Male and Female offspring underwent behavioural testing at 8 (Adult) or 15 months (Aged) of age. Brains from these animals were collected for stereological analysis of pyramidal neuron number and dendritic morphology within the CA1 and CA3 regions of the dorsal hippocampus. Prenatal ethanol exposed animals did not differ in spatial learning or memory performance in the Morris water maze or Y maze tasks compared to Control offspring. There was no effect of prenatal ethanol exposure on pyramidal cell number or density within the dorsal hippocampus. Overall, this study indicates that chronic low dose prenatal ethanol exposure in this model does not have long term detrimental effects on pyramidal cells within the dorsal hippocampus or impair spatial learning and memory performance. PMID:24978807

The acute effect of ethanol on adrenal cortex in female rats--possible role of nitric oxide.

PubMed

Dikić, Dragoslava; Budeč, Mirela; Vranješ-Durić, Sanja; Koko, Vesna; Vignjević, Sanja; Mitrović, Olivera

2011-01-01

The present study was designed to investigate a possible role of endogenous nitric oxide (NO) in the adrenal response to an acute alcohol administration in female rats. To this end, N(ω)-nitro-L-arginine-methyl ester (L-NAME), a competitive inhibitor of all isoforms of NO synthase, was used. Adult female Wistar rats showing diestrus Day 1 were treated with: (a) ethanol (2 or 4 g/kg, intraperitoneally); (b) L-NAME (30 or 50 mg/kg, subcutaneously) followed by either ethanol or saline 3 h later. Untreated and saline-injected rats were used as controls. The animals were killed 30 min after last injection. Adrenal cortex was analyzed morphometrically, and plasma levels of adrenocorticotropic hormone (ACTH) and serum concentrations of corticosterone were determined. Acute ethanol treatment enhanced the levels of ACTH and corticosterone in a dose-dependent manner. Stereological analysis revealed that acute alcohol administration induced a significant increase in absolute volume of the cortex and the zona fasciculata (ZF). In addition, ethanol at a dose of 4 g/kg increased volume density and length of the capillaries in the ZF. However, other stereological parameters were unaffected by alcohol exposure. Pretreatment with both doses of L-NAME had no effect on ethanol-induced changes. Obtained findings indicate that acute ethanol treatment stimulates the activity of the adrenal cortex and that this effect is not mediated by endogenous NO in female rats under these experimental conditions.

Effects of traditional chinese medicine on endotoxin and its receptors in rats with non-alcoholic steatohepatitis.

PubMed

Gao, Yuan; Song, Lin-Xuan; Jiang, Miao-Na; Ge, Guang-Yan; Jia, Yu-Jie

2008-04-01

The aim of this research is to study the effects of traditional Chinese medicine on endotoxin and its receptors in rats with nonalcoholic steatohepatitis (NASH). Fifty-six SD rats were divided into seven groups. All the animals were fed high fatty diet for 12 weeks. Rats with non-alcoholic steatohepatitis (NASH) were treated with traditional Chinese medicine according to low-dose, middle-dose, high-dose and Lipitor from fifth week. All rats were killed at the end of 12th week. The liver pathology changes were observed under light microscope. The levels of serum lipoid, alanine aminotransferase (ALT), endotoxin (ET), tumor necrosis factor-alpha (TNF-alpha) and interleukine-1beta (IL-1beta) were determined. The expressions of CD14 and nuclear transcriptional factor kappaB (NF-kappaB) were observed by immunohistochemistry. The expressions of lipopolysaccharide binding protein (LBP), toll-like receptor-4 (TLR-4), myeloid differentiation-2 (MD-2) and induced nitric oxide synthase (iNOS) mRNA were detected by the reverse transcription polymerase chain reaction (RT-PCR). The levels of serum endotoxin in the middle dose group (0.0225 +/- 0.0112 EU/l) were lower than those in high fatty diet model group (0.2249 +/- 0.0982 EU/l) at 12th week, the difference was significant (P < 0.01). In the middle dose group, mean values of serum TNF-alpha and IL-1beta levels decreased dramatically (1.604 +/- 0.302 ng/ml and 0.052 +/- 0.024 ng/ml) compared with those in the high fatty diet model group (4.029 +/- 1.180 ng/ml and 14.944 +/- 0.491 ng/ml; P < 0.01 and P < 0.01). The expressions of CD14 and NF-kappaB in the middle dose group decreased compared with those in the high fatty diet model group. The expressions of LBP mRNA (0.284 +/- 0.105) and TLR-4 mRNA (0.290 +/- 0.123) in the middle dose group down regulated compared with those in the high fatty diet model group (1.060 +/- 0.158 and 1.261 +/- 0.368; P < 0.01 and P < 0.01). In the middle dose group MD-2 and iNOS gene expressions were 0.132 +/- 0.058 and 0.164 +/- 0.061, respectively, which were significantly lower compared with the high fatty diet model group (0.795 +/- 0.294 and 1.029 +/- 0.388; P < 0.01 and P < 0.01). The mechanism of non-alcoholic steatohepatitis (NASH) maybe related to increasing the levels of serum endotoxin, upregulating endotoxin receptors of hepatic tissue and enhancing liver inflammatory injury. Traditional Chinese medicine is a good treatment for non-alcoholic steatohepatitis (NASH). It can produce a marked effect via relieving LPS-induced liver injury.

Rewarding, Stimulant, and Sedative Alcohol Responses and Relationship to Future Binge Drinking

PubMed Central

King, Andrea C.; de Wit, Harriet; McNamara, Patrick J.; Cao, Dingcai

2015-01-01

Context Excessive consumption of alcohol is a major problem in the United States and abroad. Despite many years of study, it is unclear why some individuals drink alcohol excessively while others do not. It has been postulated that either lower or greater acute responses to alcohol, or both, depending on the limb of the breath alcohol concentration curve, contribute to propensity for alcohol misuse. Objective To prospectively assess the relationship of acute alcohol responses to future binge drinking. Design Within-subject, double-blind, placebo-controlled, multidose laboratory alcohol challenge study with intensive follow-up. Each participant completed 3 randomized sessions examining responses to a high (0.8 g/kg) and low (0.4 g/kg) alcohol dose and placebo, followed by quarterly assessments for 2 years examining drinking behaviors and alcohol diagnoses. Setting Participants recruited from the community. Participants High-risk heavy social drinkers aged 21 to 35 years who habitually engage in weekly binge drinking (n=104) and light drinker controls (n=86). Intervention We conducted 570 laboratory sessions with a subsequent 99.1% follow-up (1506 of 1520). Main Outcome Measures Biphasic Alcohol Effects Scale, Drug Effects Questionnaire, cortisol response, Time-line Follow-Back, Drinker Inventory of Consequences–Recent, and DSM-IV alcohol abuse and dependence. Results Alcohol produced greater stimulant and rewarding (liking and wanting) responses and lower sedative and cortisol responses in heavy vs light drinkers. Among the heavy drinkers, greater positive effects and lower sedative effects after alcohol consumption predicted increased binge drinking frequency during follow-up. In turn, greater frequency of binge drinking during follow-up was associated with greater likelihood of meeting diagnostic criteria for alcohol abuse and dependence. Conclusions The widely held low level response theory and differentiator model should be revised: in high-risk drinkers, stimulant and rewarding alcohol responses even at peak breath alcohol concentrations are important predictors of future alcohol problems. Trial Registration clinicaltrials.gov Identifier: NCT00961792 PMID:21464363

Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach.

PubMed

Lachenmeier, Dirk W; Rehm, Jürgen

2015-01-30

A comparative risk assessment of drugs including alcohol and tobacco using the margin of exposure (MOE) approach was conducted. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Median lethal dose values from animal experiments were used to derive the benchmark dose. The human intake was calculated for individual scenarios and population-based scenarios. The MOE was calculated using probabilistic Monte Carlo simulations. The benchmark dose values ranged from 2 mg/kg bodyweight for heroin to 531 mg/kg bodyweight for alcohol (ethanol). For individual exposure the four substances alcohol, nicotine, cocaine and heroin fall into the "high risk" category with MOE < 10, the rest of the compounds except THC fall into the "risk" category with MOE < 100. On a population scale, only alcohol would fall into the "high risk" category, and cigarette smoking would fall into the "risk" category, while all other agents (opiates, cocaine, amphetamine-type stimulants, ecstasy, and benzodiazepines) had MOEs > 100, and cannabis had a MOE > 10,000. The toxicological MOE approach validates epidemiological and social science-based drug ranking approaches especially in regard to the positions of alcohol and tobacco (high risk) and cannabis (low risk).

Safety reports on the off-label use of baclofen for alcohol-dependence: recommendations to improve causality assessment.

PubMed

Rolland, Benjamin; Auffret, Marine; Franchitto, Nicolas

2016-06-01

The off-label use of high-dose baclofen (HDB) for alcohol-dependence has recently spread. However, HDB has been associated with numerous reports of adverse events (AEs). Pharmacovigilance reporting is supposed to differentiate AEs from adverse drug reactions (ADRs), for which the causality of the drug is determined using validated methods. Since 2010, we found 20 publications on baclofen-related AEs in alcohol dependence, in Medline-referenced journals or national pharmacovigilance reports. We focused on whether these reports used causality algorithms, and provided essential elements for determining baclofen causality and excluding the involvement of alcohol and other psychoactive substances or psychotropic drugs. In half of the cases, no causality algorithm was used. Detailed information on baclofen dosing was found in 17 out of 20 (85%) articles, whereas alcohol doses were given only in 10 (50%) publications. Other psychoactive substances and psychotropic drugs were broached in 14 (70%) publications. future publications reporting suspected HDB-induced ADRs should use validated causality algorithms and provide sufficient amount of contextual information for excluding other potential causes. For HDB, the psychiatric history, and the longitudinal description of alcohol consumptions and associated doses of psychoactive substances or psychotropic medications should be detailed for every reported case.

Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach

PubMed Central

Lachenmeier, Dirk W.; Rehm, Jürgen

2015-01-01

A comparative risk assessment of drugs including alcohol and tobacco using the margin of exposure (MOE) approach was conducted. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Median lethal dose values from animal experiments were used to derive the benchmark dose. The human intake was calculated for individual scenarios and population-based scenarios. The MOE was calculated using probabilistic Monte Carlo simulations. The benchmark dose values ranged from 2 mg/kg bodyweight for heroin to 531 mg/kg bodyweight for alcohol (ethanol). For individual exposure the four substances alcohol, nicotine, cocaine and heroin fall into the “high risk” category with MOE < 10, the rest of the compounds except THC fall into the “risk” category with MOE < 100. On a population scale, only alcohol would fall into the “high risk” category, and cigarette smoking would fall into the “risk” category, while all other agents (opiates, cocaine, amphetamine-type stimulants, ecstasy, and benzodiazepines) had MOEs > 100, and cannabis had a MOE > 10,000. The toxicological MOE approach validates epidemiological and social science-based drug ranking approaches especially in regard to the positions of alcohol and tobacco (high risk) and cannabis (low risk). PMID:25634572

The effects of nicotine on ethanol-induced conditioned taste aversions in Long-Evans rats.

PubMed

Rinker, Jennifer A; Busse, Gregory D; Roma, Peter G; Chen, Scott A; Barr, Christina S; Riley, Anthony L

2008-04-01

Overall drug acceptability is thought to be a function of the balance between its rewarding and aversive effects, the latter of which is reportedly affected by polydrug use. Given that nicotine and alcohol are commonly co-used, the present experiments sought to assess nicotine's impact on ethanol's aversive effects within a conditioned taste aversion design. Experiment 1 examined various doses of nicotine (0, 0.4, 0.8, 1.2 mg/kg) to determine a behaviorally active dose, and experiment 2 examined various doses of ethanol (0, 0.5, 1.0, 1.5 g/kg) to determine a dose that produced intermediate aversions. Experiment 3 then examined the aversive effects of nicotine (0.8 mg/kg) and ethanol (1.0 g/kg) alone and in combination. Additionally, nicotine's effects on blood alcohol concentrations (BAC) and ethanol-induced hypothermia were examined. Nicotine and ethanol combined produced aversions significantly greater than those produced by either drug alone or the summed aversive effects of the individual compounds. These effects were unrelated to changes in BAC, but nicotine and ethanol combined produced a prolonged hypothermic effect which may contribute to the increased aversions induced by the combination. These data demonstrate that nicotine may interact with ethanol, increasing ethanol's aversive effects. Although the rewarding effects of concurrently administered nicotine and ethanol were not assessed, these data do indicate that the reported high incidence of nicotine and ethanol co-use is unlikely due to reductions in the aversiveness of ethanol with concurrently administered nicotine. It is more likely attributable to nicotine-related changes in ethanol's rewarding effects.

The selective kappa-opioid receptor agonist U50,488H attenuates voluntary ethanol intake in the rat.

PubMed

Lindholm, S; Werme, M; Brené, S; Franck, J

2001-05-01

Non-selective opioid receptor antagonists are increasingly used in the treatment of alcohol dependence. The clinical effects are significant but the effect size is rather small and unpleasant side effects may limit the benefits of the compounds. Ligands acting at mu- and/or delta- receptors can alter the voluntary intake of ethanol in various animal models. Therefore, the attenuating effects of selective opioid receptor ligands on ethanol intake may be of clinical interest in the treatment of alcoholism. The objective of this study was to examine the effects of a selective kappa-receptor agonist, U50,488H on voluntary ethanol intake in the rat. We used a restricted access model with a free choice between an ethanol solution (10% v/v) and water. During the 3-days baseline period, the rats received a daily saline injection (1 ml/kg, i.p.) 15 min before the 2 h access to ethanol. The animals had free access to water at all times. The control group received a daily saline injection during the 4-days treatment-period, whereas the treatment groups received a daily dose of U50,488H (2.5, 5.0 or 10 mg/kg per day). Animals treated with U50,488H dose-dependently decreased their ethanol intake. The effect of the highest dose of U50,488H was reduced by pre-treatment with the selective kappa-antagonist nor-binaltorphimine (nor-BNI). These results demonstrate that activation of kappa-opioid receptors can attenuate voluntary ethanol intake in the rat, and the data suggest that the brain dynorphin/kappa-receptor systems may represent a novel target for pharmacotherapy in the treatment of alcohol dependence.

[Alcohol intake--a two-edged sword. Part 1: metabolism and pathogenic effects of alcohol].

PubMed

Ströhle, Alexander; Wolters, Maike; Hahn, Andreas

2012-08-01

From the biomedical point of view alcohol is a Janus-faced dietary component with a dose-dependent effect varying from cardiovascular protection to cytotoxicity. Alcohol is absorbed in the upper gastrointestinal tract by passive diffusion, is quickly distributed throughout body water and is mostly eliminated through oxidation. The enzymatically-catalyzed oxidative degradation to acetaldehyde and further to acetate is primarily localized in the liver. In case of a low blood alcohol concentration (<0.5 per thousand) alcohol is predominantely metabolized by the enzyme aldehyde dehydrogenase; higher blood concentrations (>0.5 per thousand) are increasingly oxidized by the microsomal ethanoloxidizing system (MEOS). Alcohol consumption induces several metabolic reactions as well as acute effects on the central nervous system. Chronic alcohol consumption to some extent irreparably damages nearly every organ with the liver being particularly concerned. There are three stages of alcohol-induced liver disease (fatty liver, alcohol hepatitis, liver cirrhosis) and the liver damages mainly result from reaction products of alcohol degradation (acetaldehyde, NADH and reactive oxygen species). An especially dreaded clinical complication of the alcohol-induced liver disease is the hepatic encephalopathy. Its pathogenesis is a multifactorial and self-perpetuating process with the swelling of astrocytes being a crucial point. Swollen astrocytes induce several reactions such as oxidative/nitrosative stress, impaired signal transduction, protein modifications and a modified gene expression profile. The swelling of astrocytes and the change in neuronal activity are attributed to several neurotoxins, especially ammonia and aromatic amino acids. In alcohol addicted subjects multiple micronutrient deficiencies are common. The status of folic acid, thiamine, pyridoxine and zinc is especially critical.

Anxiety, Sedation, and Simulated Driving in Binge Drinkers

PubMed Central

Aston, Elizabeth R.; Shannon, Erin E.; Liguori, Anthony

2014-01-01

The current study evaluated the relationships among trait anxiety, subjective response to alcohol, and simulated driving following a simulated alcohol binge. Sixty drinkers with a binge history completed the State Trait Anxiety Inventory (STAI), the Alcohol Use Questionnaire, and subsequently completed a driving simulation. Participants were then administered 0.2 g/kg ethanol at 30 minute intervals (cumulative dose 0.8 g/kg). Following alcohol consumption, the Biphasic Alcohol Effects Scale (BAES) and visual analog scales of subjective impairment and driving confidence were administered, after which simulated driving was re-assessed. Due to the emphasis on simulated driving after drinking in the current study, subjective response to alcohol (i.e., self-reported sedation, stimulation, impairment, and confidence in driving ability) was assessed once following alcohol consumption, as this is the time when drinkers tend to make decisions regarding legal driving ability. Alcohol increased driving speed, speeding tickets, and collisions. Sedation following alcohol predicted increased subjective impairment and decreased driving confidence. Subjective impairment was not predicted by sensitivity to stimulation or trait anxiety. High trait anxiety predicted low driving confidence after drinking and this relationship was mediated by sedation. Increased speed after alcohol was predicted by sedation, but not by trait anxiety or stimulation. Anxiety, combined with the sedating effects of alcohol, may indicate when consumption should cease. However, once driving is initiated, sensitivity to sedation following alcohol consumption is positively related to simulated driving speed. PMID:24955664

Brain alcohol detectability in human subjects with and without a paternal history of alcoholism.

PubMed

Chiu, Tak-Ming; Mendelson, Jack H; Sholar, Michelle B; Mutschler, Nicole H; Wines, James D; Hesselbrock, Victor M; Mello, Nancy K

2004-01-01

This study examined the putative effects of a paternal history of alcoholism on the apparent detectability of brain alcohol in human subjects. Brain to blood ethanol ratios in two cohorts of men were determined, using proton magnetic resonance spectroscopic imaging in a brain voxel (2 x 2 x 2 cm) containing the putamen. The men were light drinkers with a positive (n = 8) or a negative (n = 8) paternal history of alcoholism and were given an alcohol dose of 0.8 g/kg body weight. In both groups, brain alcohol detectability was less than 100%. No significant difference (p = .37) was found in the brain/blood ethanol ratios of the two groups. However, subjective assessments of feeling the extreme effects of alcohol and the extent of intoxication ("how drunk") were highly correlated with a paternal history of alcoholism, with the paternal history negative group reporting significantly more intense feelings of intoxication. A review of existing literature evidence and data obtained in this study indicate that brain alcohol detectability via magnetic resonance spectroscopic imaging is less than 100%. There were no significant differences in brain alcohol detectability between paternal history positive and paternal history negative men. Differences in the Subjective High Assessment Scale ratings between the two groups, however, indicate the importance of a genetic influence on the subjective response to alcohol.

Honey reduces blood alcohol concentration but not affects the level of serum MDA and GSH-Px activity in intoxicated male mice models.

PubMed

Shi, Peiying; Chen, Bing; Chen, Conghai; Xu, Jingyang; Shen, Zhenhuang; Miao, Xiaoqing; Yao, Hong

2015-07-14

For a long time, honey was purportedly helpful to prevent drunkenness and relieve hangover symptoms. However, few of the assertions have experienced scientific assessment. The present study examined the effects of honey on intoxicated male mice. Low or high doses of lychee flower honey (2.19 or 4.39 g/kg body weight, respectively) were single orally administrated 30 min before the ethanol intoxication of mice, followed by recording the locomotor activity by autonomic activity instrument and observing the climbing ability after alcohol. On the other hand, 2.19 g/kg honey was single orally administrated 5 min after the ethanol intoxication of mice, followed by determining the ethanol concentration in mice blood. In addition, subacute alcoholism mice models were developed and after the treatment of 2.19 g/kg honey s.i.d for successive three days, the level of serum malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) activity were detected in the models. Both of the two doses of honey increased the autonomic activity of alcoholized mice. Furthermore, the treatment of 2.19 g/kg honey could decrease significantly the blood ethanol concentration in intoxicated mice. The anti-intoxication activity of honey could be due to the effect of the fructose contained in the honey. Meanwhile, honey could not affect the serum MDA level and GSH-Px activity in alcoholism mice models. Honey indeed possesses anti-intoxication activity.

Topiramate in the treatment of substance related disorders: a critical review of the literature

PubMed Central

Shinn, Ann K.; Greenfield, Shelly F.

2013-01-01

Objective To critically review the literature on topiramate in the treatment of substance related disorders. Data Sources A PubMed search of human studies published in English through January 2009. Study Selection 26 articles were identified and reviewed; these studies examined topiramate in disorders related to alcohol, nicotine, cocaine, methamphetamine, opioids, ecstasy, and benzodiazepines. Data Extraction Study design, sample size, topiramate dose and duration, and study outcomes were reviewed. Data Synthesis There is compelling evidence for the efficacy of topiramate in the treatment of alcohol dependence. Two trials show trends for topiramate’s superiority over oral naltrexone in alcohol dependence, while one trial suggests topiramate is inferior to disulfiram. Despite suggestive animal models, evidence for topiramate in treating alcohol withdrawal in humans is slim. Studies of topiramate in nicotine dependence show mixed results. Human laboratory studies that used acute topiramate dosing show that topiramate actually enhances the pleasurable effects of both nicotine and methamphetamine. Evidence for topiramate in the treatment of cocaine dependence is promising, but limited by small sample size. The data on opioids, benzodiazepines, and ecstasy are sparse. Conclusion Topiramate is efficacious for the treatment of alcohol dependence, but side effects may limit widespread use. While topiramate’s unique pharmacodynamic profile offers a promising theoretical rationale for use across multiple substance related disorders, heterogeneity both across and within these disorders limits topiramate’s broad applicability in treating substance related disorders. Recommendations for future research include exploration of genetic variants for more targeted pharmacotherapies. PMID:20361908

Selective effects of acute alcohol intake on the prospective and retrospective components of a prospective-memory task with emotional targets.

PubMed

Walter, Nora T; Bayen, Ute J

2016-01-01

Prospective memory involves remembering to do something in the future and has a prospective component (remembering that something must be done) and a retrospective component (remembering what must be done and when it must be done). Initial studies reported an impairment in prospective-memory performance due to acute alcohol consumption. Retrospective-memory studies demonstrated that alcohol effects vary depending on the emotionality of the information that needs to be learned. The aim of the present study was to investigate possible differential effects of a mild acute alcohol dose (0.4 g/kg) on the prospective and retrospective components of prospective memory depending on cue valence. Seventy-five participants were allocated to an alcohol or placebo group and performed a prospective-memory task in which prospective-memory cue valence was manipulated (negative, neutral, positive). The multinomial model of event-based prospective memory (Smith and Bayen 2004) was used to measure alcohol and valence effects on the two prospective-memory components separately. Overall, no main effect of alcohol or valence on prospective-memory performance occurred. However, model-based analyses demonstrated a significantly higher retrospective component for positive compared with negative cues in the placebo group. In the alcohol group, the prospective component was weaker for negative than for neutral cues and the retrospective component was stronger for positive than for neutral cues. Group comparisons showed that the alcohol group had a significantly lower prospective component for negative cues and a lower retrospective component for neutral cues. This is the first study to demonstrate selective alcohol effects on prospective-memory components depending on prospective-memory cue valence.

The phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice.

PubMed

Liu, Xin; Hao, Pi-Da; Yang, Ming-Feng; Sun, Jing-Yi; Mao, Lei-Lei; Fan, Cun-Dong; Zhang, Zong-Yong; Li, Da-Wei; Yang, Xiao-Yi; Sun, Bao-Liang; Zhang, Han-Ting

2017-08-01

Alcohol use disorders have become one of the most damaging psychiatric disorders in the world; however, there are no ideal treatments in clinic. Phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes intracellular cyclic AMP (cAMP), has been involved in alcohol use disorders. Roflumilast is the first PDE4 inhibitor approved for treatment of chronic obstructive pulmonary diseases in clinic. It was of particular interest to researchers to determine whether roflumilast altered ethanol consumption. The present study tried to determine the effects of roflumilast on ethanol intake and preference. We used the two-bottle choice paradigm to assess ethanol intake and preference in C57BL/6J mice treated with roflumilast (1, 3, or 10 mg/kg) or rolipram (0.5 mg/kg; positive control). The effect of roflumilast was verified using the ethanol drinking-in-dark (DID) test. Locomotor activity was examined using the open-field test. Intake of sucrose or quinine was also tested to determine whether natural reward preference and aversive stimuli were involved in the effect of PDE4 inhibitors. Similar to rolipram, roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in a dose-dependent manner, with significant changes at the dose of 10 mg/kg; in contrast, roflumilast did not affect sucrose or quinine drinking, although it decreased locomotor activity at the high dose within 3 h of treatment. These data provide novel demonstration for the effect of roflumilast on ethanol consumption and suggest that roflumilast may be beneficial for treatment of alcoholism.

The highly selective orexin/hypocretin 1 receptor antagonist GSK1059865 potently reduces ethanol drinking in ethanol dependent mice.

PubMed

Lopez, Marcelo F; Moorman, David E; Aston-Jones, Gary; Becker, Howard C

2016-04-01

The orexin/hypocretin (ORX) system plays a major role in motivation for natural and drug rewards. In particular, a number of studies have shown that ORX signaling through the orexin 1 receptor (OX1R) regulates alcohol seeking and consumption. Despite the association between ORX signaling and motivation for alcohol, no study to date has investigated what role the ORX system plays in alcohol dependence, an understanding of which would have significant clinical relevance. This study was designed to evaluate the effect of the highly selective OX1R antagonist GSK1059865 on voluntary ethanol intake in ethanol-dependent and control non-dependent mice. Mice were subjected to a protocol in which they were evaluated for baseline ethanol intake and then exposed to intermittent ethanol or air exposure in inhalation chambers. Each cycle of chronic intermittent ethanol (CIE), or air, exposure was followed by a test of ethanol intake. Once the expected effect of increased voluntary ethanol intake was obtained in ethanol dependent mice, mice were tested for the effect of GSK1059865 on ethanol and sucrose intake. Treatment with GSK1059865 significantly decreased ethanol drinking in a dose-dependent manner in CIE-exposed mice. In contrast GSK1059865 decreased drinking in air-exposed mice only at the highest dose used. There was no effect of GSK1059865 on sucrose intake. Thus, ORX signaling through the OX1R, using a highly-selective antagonist, has a profound influence on high levels of alcohol drinking induced in a dependence paradigm, but limited or no influence on moderate alcohol drinking or sucrose drinking. These results indicate that the ORX system may be an important target system for treating disorders of compulsive reward seeking such as alcoholism and other addictions in which motivation is strongly elevated. Copyright © 2016 Elsevier B.V. All rights reserved.

The effectiveness of an intervention to reduce alcohol-related violence in premises licensed for the sale and on-site consumption of alcohol: a randomized controlled trial.

PubMed

Moore, Simon C; Alam, M Fasihul; Heikkinen, Marjukka; Hood, Kerenza; Huang, Chao; Moore, Laurence; Murphy, Simon; Playle, Rebecca; Shepherd, Jonathan; Shovelton, Claire; Sivarajasingam, Vaseekaran; Williams, Anne

2017-11-01

Premises licensed for the sale and consumption of alcohol can contribute to levels of assault-related injury through poor operational practices that, if addressed, could reduce violence. We tested the real-world effectiveness of an intervention designed to change premises operation, whether any intervention effect changed over time, and the effect of intervention dose. A parallel randomized controlled trial with the unit of allocation and outcomes measured at the level of individual premises. All premises (public houses, nightclubs or hotels with a public bar) in Wales, UK. A randomly selected subsample (n = 600) of eligible premises (that had one or more violent incidents recorded in police-recorded crime data; n = 837) were randomized into control and intervention groups. Intervention premises were audited by Environmental Health Practitioners who identified risks for violence and provided feedback by varying dose (informal, through written advice, follow-up visits) on how risks could be addressed. Control premises received usual practice. Police data were used to derive a binary variable describing whether, on each day premises were open, one or more violent incidents were evident over a 455-day period following randomization. Due to premises being unavailable at the time of intervention delivery 208 received the intervention and 245 were subject to usual practice in an intention-to-treat analysis. The intervention was associated with an increase in police recorded violence compared to normal practice (hazard ratio = 1.34, 95% confidence interval = 1.20-1.51). Exploratory analyses suggested that reduced violence was associated with greater intervention dose (follow-up visits). An Environmental Health Practitioner-led intervention in premises licensed for the sale and on-site consumption of alcohol resulted in an increase in police recorded violence. © 2017 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Efficacy of maternal choline supplementation during pregnancy in mitigating adverse effects of prenatal alcohol exposure on growth and cognitive function: A randomized, double-blind, placebo-controlled clinical trial.

PubMed

Jacobson, Sandra W; Carter, R Colin; Molteno, Christopher D; Stanton, Mark E; Herbert, Jane; Lindinger, Nadine M; Lewis, Catherine E; Dodge, Neil C; Hoyme, H Eugene; Zeisel, Steven H; Meintjes, Ernesta M; Duggan, Christopher P; Jacobson, Joseph L

2018-05-11

We recently demonstrated the acceptability and feasibility of a randomized, double-blind choline supplementation intervention for heavy drinking women during pregnancy. In this paper, we report our results relating to the efficacy of this intervention in mitigating adverse effects of prenatal alcohol exposure on infant growth and cognitive function. 69 Cape Coloured (mixed ancestry) heavy drinkers in Cape Town, South Africa, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of either 2 g of choline or placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. The primary outcome, eyeblink conditioning (EBC), was assessed at 6.5 months. Somatic growth was measured at birth, 6.5, and 12 months; recognition memory and processing speed on the Fagan Test of Infant Intelligence, at 6.5 and 12 months. Infants born to choline-treated mothers were more likely to meet criterion for conditioning on EBC than the placebo group. Moreover, within the choline arm, degree of maternal adherence to the supplementation protocol strongly predicted EBC performance. Both groups were small at birth, but choline-treated infants showed considerable catch-up growth in weight and head circumference at 6.5 and 12 months. At 12 months, the infants in the choline treatment arm had higher novelty preference scores, indicating better visual recognition memory. This exploratory study is the first to provide evidence that a high dose of choline administered early in pregnancy can mitigate adverse effects of heavy prenatal alcohol exposure on EBC, postnatal growth, and cognition in human infants. These findings are consistent with studies of alcohol-exposed animals that have demonstrated beneficial effects of choline supplementation on classical conditioning, learning, and memory. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Dose-effect relation between daily ethanol intake in the range 0-70 grams and %CDT value: validation of a cut-off value.

PubMed

Schellenberg, François; Schwan, Raymund; Mennetrey, Louise; Loiseaux, Marie-Nadia; Pagès, Jean Christophe; Reynaud, Michel

2005-01-01

To evaluate the ability to infer alcohol consumption using the %CDT (carbohydrate deficient transferrin) immunoassay (Axis Shield). One hundred and eighty-three healthy subjects (143 men, 40 women) undergoing a routine medical check-up at their workplace declared frequency and quantity of alcohol consumption covering the last 4 weeks. Seven sub-groups were made up from this population, according to daily ethanol intake and by increments of 10 g from 0 to 70 g/day. A reference group that consisted of 133 healthy teetotallers (74 men, 59 women) was recruited by occupational medicine in the same conditions as the 183 subjects of the study. Percentage CDT and gamma glutamyl transferase (GGT) were assayed on a fasting blood sample. There was a proportional dose-response effect of daily ethanol intake on %CDT values in the range of 0-70 g per day. A threshold effect on %CDT values for patients having an alcohol intake of over 40 g per day was found, an effect which was not observed for GGT activity. The kit has clinical usefulness, and the value of 2.6% proposed by the manufacturer for the cut-off for hazardous drinking in both sexes has been validated.

Effect of hydro-alcoholic extract of Vernonia cinerea Less. against ethylene glycol-induced urolithiasis in rats.

PubMed

Hiremath, Ravindra D; Jalalpure, Sunil S

2016-01-01

Aim of this study is to evaluate antiurolithiatic potential of whole plant hydro-alcoholic (30:70) extract of Vernonia cinerea Less. in accordance to its claims made in ancient literature and also being one of the ingredients of cystone, a marketed formulation widely used in the management of urolithiasis. To induce urolithiasis, 0.75% v/v ethylene glycol was administered orally for 14 days. The curative dose of 400 mg/kg b.w. and preventive doses of 100, 200, and 400 mg/kg b.w. were administered from 15 th to 28 th and 1 st to 28 days, respectively. Cystone 750 mg/kg b.w. was selected as the reference standard for both curative and preventive doses. On 28 th day, urinate of 24 h was collected and subjected for estimation of calcium, oxalate, and phosphates. Serum biochemical and kidney homogenate analysis was done for determination of renal oxalate contents. The diseased Group II showed marked increase ( P < 0.001 vs. normal Group I) in levels of urine calcium, oxalate, and phosphate. Serum creatinine, urea, and uric acid levels were also increased. Histopathological studies of kidney sections revealed significant changes. Treatment with hydro-alcoholic extract of V. cinerea showed significant ( P < 0.01 vs. calculi-induced Group II) dose-dependent activity. A progressive increase in urine output, body weight, and decline in concentrations of stone-forming components such as calcium, oxalates, and phosphates was observed. It can be inferred that V. cinerea Less. is effective in ethylene glycol-induced urolithiasis and may have a potential in preventing and curing urolithiasis.

[Eulogy of wine?].

PubMed

Godfroid, I O

1997-12-20

In the literature the beneficial effects on health of drinking alcoholic beverages, especially red wine, is becoming increasingly more evident. We report an objective analysis of the advantages and the dangers of such a tendency. It appears that the daily consumption of red wine at moderate doses (200-400 ml a day) has real prophylactic effects. These are particularly marked in the prevention of coronary heart disease (CHD), but also for a possible cancer chemopreventive activity, in the prevention of type II diabetes, of ischemic stroke, of osteoporosis in older women, and of Alzheimer's disease. But, inasmuch as the consumption of alcoholic beverages always involves a potential danger (organic diseases, risk of dependence, alcoholism), from a medical point of view eulogy to wine is ethically indefensible. Similar effects may be obtained from a diet rich in fruits and fresh vegetables.

Sigma-1 Receptor Mediates Acquisition of Alcohol Drinking and Seeking behavior in Alcohol-Preferring Rats

PubMed Central

Blasio, Angelo; Valenza, Marta; Iyer, Malliga R.; Rice, Kenner C.; Steardo, Luca; Hayashi, T.; Cottone, Pietro; Sabino, Valentina

2015-01-01

Sigma-1 receptor (Sig-1R) has been proposed as a novel therapeutic target for drug and alcohol addiction. We have shown previously that Sig-1R agonists facilitate the reinforcing effects of ethanol and induce binge-like drinking, while Sig-1R antagonists block excessive drinking in both genetic and environmental models of alcoholism, without affecting intake in outbred non-dependent rats. Even though significant progress has been made in understanding the function of Sig-1Rs in alcohol reinforcement, its role in the early and late stage of alcohol addiction remains unclear. Administration of the selective Sig-1R antagonist BD-1063 dramatically reduced the acquisition of alcohol drinking behavior as well as the preference for alcohol in genetically selected TSRI Sardinian alcohol preferring (Scr:sP) rats; the treatment had no effect on total fluid intake, food intake or body weight gain, proving selectivity of action. Furthermore, BD-1063 dose-dependently decreased alcohol-seeking behavior in rats trained under a second-order schedule of reinforcement, in which responding is maintained by contingent presentation of a conditioned reinforcer. Finally, an innate elevation in Sig-1R protein levels was found in the nucleus accumbens of alcohol-preferring Scr:sP rats, compared to outbred Wistar rats, alteration which was normalized by chronic, voluntary alcohol drinking. Taken together these findings demonstrate that Sig-1R blockade reduces the propensity to both acquire alcohol drinking and to seek alcohol, and point to the nucleus accumbens as a potential key region for the effects observed. Our data suggest that Sig-1R antagonists may have therapeutic potential in multiple stages of alcohol addiction. PMID:25848705

Sigma-1 receptor mediates acquisition of alcohol drinking and seeking behavior in alcohol-preferring rats.

PubMed

Blasio, Angelo; Valenza, Marta; Iyer, Malliga R; Rice, Kenner C; Steardo, Luca; Hayashi, T; Cottone, Pietro; Sabino, Valentina

2015-01-01

Sigma-1 receptor (Sig-1R) has been proposed as a novel therapeutic target for drug and alcohol addiction. We have shown previously that Sig-1R agonists facilitate the reinforcing effects of ethanol and induce binge-like drinking, while Sig-1R antagonists on the other hand block excessive drinking in genetic and environmental models of alcoholism, without affecting intake in outbred non-dependent rats. Even though significant progress has been made in understanding the function of Sig-1R in alcohol reinforcement, its role in the early and late stage of alcohol addiction remains unclear. Administration of the selective Sig-1R antagonist BD-1063 dramatically reduced the acquisition of alcohol drinking behavior as well as the preference for alcohol in genetically selected TSRI Sardinian alcohol preferring (Scr:sP) rats; the treatment had instead no effect on total fluid intake, food intake or body weight gain, proving selectivity of action. Furthermore, BD-1063 dose-dependently decreased alcohol-seeking behavior in rats trained under a second-order schedule of reinforcement, in which responding is maintained by contingent presentation of a conditioned reinforcer. Finally, an innate elevation in Sig-1R protein levels was found in the nucleus accumbens of alcohol-preferring Scr:sP rats, compared to outbred Wistar rats, alteration which was normalized by chronic, voluntary alcohol drinking. Taken together these findings demonstrate that Sig-1R blockade reduces the propensity to both acquire alcohol drinking and to seek alcohol, and point to the nucleus accumbens as a potential key region for the effects observed. Our data suggest that Sig-1R antagonists may have therapeutic potential in multiple stages of alcohol addiction. Copyright © 2015 Elsevier B.V. All rights reserved.

A Randomized, Placebo-Controlled Study of High-Dose Baclofen in Alcohol-Dependent Patients-The ALPADIR Study.

PubMed

Reynaud, Michel; Aubin, Henri-Jean; Trinquet, Francoise; Zakine, Benjamin; Dano, Corinne; Dematteis, Maurice; Trojak, Benoit; Paille, Francois; Detilleux, Michel

2017-07-01

Alcohol dependence is a major public health issue with a need for new pharmacological treatments. The ALPADIR study assessed the efficacy and safety of baclofen at the target dose of 180 mg/day for the maintenance of abstinence and the reduction in alcohol consumption in alcohol-dependent patients. Three hundred and twenty adult patients (158 baclofen and 162 placebo) were randomized after alcohol detoxification. After a 7-week titration, the maintenance dose was provided for 17 weeks, then progressively decreased over 2 weeks before stopping. The percentage of abstinent patients during 20 consecutive weeks (primary endpoint) was low (baclofen: 11.9%; placebo: 10.5%) and not significantly different between groups (OR 1.20; 95%CI: 0.58 to 2.50; P = 0.618). A reduction in alcohol consumption was observed from month 1 in both groups, but the difference of 10.9 g/day at month 6 between groups, in favour of baclofen, was not statistically significant (P = 0.095). In a subgroup of patients with high drinking risk level at baseline, the reduction was greater with a difference at month 6 of 15.6 g/day between groups in favour of baclofen (P = 0.089). The craving assessed with Obsessive-Compulsive Drinking Scale significantly decreased in the baclofen group (P = 0.017). No major safety concern was observed. This study did not demonstrate the superiority of baclofen in the maintenance of abstinence at the target dose of 180 mg/day. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen. Baclofen was assessed versus placebo for maintenance of abstinence and reduction in alcohol consumption in alcohol-dependent patients. This study did not demonstrate the superiority of baclofen in the maintenance of abstinence. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Randomised clinical trial: a leucine-metformin-sildenafil combination (NS-0200) vs placebo in patients with non-alcoholic fatty liver disease.

PubMed

Chalasani, N; Vuppalanchi, R; Rinella, M; Middleton, M S; Siddiqui, M S; Barritt, A S; Kolterman, O; Flores, O; Alonso, C; Iruarrizaga-Lejarreta, M; Gil-Redondo, R; Sirlin, C B; Zemel, M B

2018-06-01

Sirtuin 1 (Sirt1) is suppressed in non-alcoholic fatty liver disease (NAFLD), while its' stimulation or overexpression results in reduced disease severity in pre-clinical NAFLD models. Leucine allosterically activates Sirt1 and synergise with other Sirt/AMPK/NO pathway activators. We developed a triple combination of leucine, metformin and sildenafil (NS-0200), which was effective in a mouse model of non-alcoholic steatohepatitis (NASH). To report the results from a Phase 2, randomised clinical trial of of NS-0200 in 91 subjects with NAFLD (liver fat ≥15% by magnetic resonance imaging-proton-density fat fraction (MRI-PDFF)). Subjects were randomised to placebo, low-dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil) or high-dose NS-0200 (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) b.d. for 16 weeks; change in hepatic fat was assessed via MRI-PDFF, and lipid metabolism was assessed via changes in the lipidomic signature. Seventy subjects completed the trial and met a priori compliance criteria. Analyses were conducted on the full cohort and on those with alanine aminotransferase (ALT) values above median (50 U/L; n = 35). In the full cohort, active treatments did not separate from placebo. High dose NS-0200 reduced hepatic fat by 15.7% (relative change from baseline) in the high ALT group (P < 0.005) while low dose NS-0200 and placebo did not significantly change hepatic fat. Lipidomic analysis showed dose-responsive treatment effects in both overall and high ALT cohorts, with significant decreases in metabolically active lipids and up-regulation of fatty acid oxidation. These data support further evaluation of high-dose NS-0200 for treating NASH, especially in those with elevated ALT (NCT 02546609). © 2018 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

The Combined Effects of Alcohol, Caffeine and Expectancies on Subjective Experience, Impulsivity and Risk-Taking

PubMed Central

Heinz, Adrienne J.; de Wit, Harriet; Lilje, Todd C.; Kassel, Jon D.

2013-01-01

Caffeinated alcoholic beverage (CAB) consumption is a rapidly growing phenomenon among young adults and is associated with a variety of health-risk behaviors. The current study examined whether either caffeinated alcohol or the expectation of receiving caffeinated alcohol altered affective, cognitive and behavioral outcomes hypothesized to contribute to risk behavior. Young adult social drinkers (N=146) participated in a single session where they received alcohol (peak Breath Alcohol Content = .088 g/dL, SD = .019; equivalent to about 4 standard drinks) and were randomly assigned to one of four further conditions 1) no caffeine, no caffeine expectancy, 2) caffeine and caffeine expectancy, 3) no caffeine but caffeine expectancy, 4) caffeine but no caffeine expectancy. Participants’ habitual CAB consumption was positively correlated with measures of impulsivity and risky behavior, independently of study drugs. Administration of caffeine (mean dose = 220 mg, SD = 38; equivalent to about 2.75 Red Bulls) in the study reduced subjective ratings of intoxication and reversed the decrease in desire to continue drinking, regardless of expectancy. Caffeine also reduced the effect of alcohol on inhibitory reaction time (faster incorrect responses). Participants not expecting caffeine were less attentive after alcohol, whereas participants expecting caffeine were not, regardless of caffeine administration. Alcohol decreased response accuracy in all participants except those who both expected and received caffeine. Findings suggest that CABs may elevate risk for continued drinking by reducing perceived intoxication, and by maintaining the desire to continue drinking. Simply expecting to consume caffeine may reduce the effects of alcohol on inattention, and either expecting or consuming caffeine may protect against other alcohol-related performance decrements. Caffeine, when combined with alcohol, has both beneficial and detrimental effects on mechanisms known to contribute to risky behavior. PMID:23750693

UPDATE ON NEUROPHARMACOLOGICAL TREATMENTS FOR ALCOHOLISM: SCIENTIFIC BASIS AND CLINICAL FINDINGS

PubMed Central

JOHNSON, BANKOLE A.

2008-01-01

The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol dependence. The Food and Drug Administration (FDA)–approved medications naltrexone and acamprosate have shown mixed results in clinical trials. Oral naltrexone and naltrexone depot formulations have generally demonstrated efficacy at treating alcohol dependence, but their treatment effect size is small, and more research is needed to compare the effects of different doses on drinking outcome. Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. In U.S. trials, acamprosate has not proved to be efficacious. Research continues to explore which types of alcohol-dependent individual would benefit the most from treatment with naltrexone or acamprosate. The combination of the two medications demonstrated efficacy for treating alcohol dependence in one European study but not in a multi-site U.S. study. Another FDA-approved medication, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram is most effective when given to those who are highly compliant or who are receiving their medication under supervision. Of the non-approved medications, topiramate is among the most promising, with a medium effect size in clinical trials. Another promising medication, baclofen, has shown efficacy in small trials. Serotonergic agents such as selective serotonin reuptake inhibitors and the serotonin-3 receptor antagonist, ondansetron, appear to be efficacious only among certain genetic subtypes of alcoholic. As neuroscientific research progresses, other promising medications, as well as medication combinations, for treating alcohol dependence continue to be explored. PMID:17880925

Does retigabine affect the development of alcohol dependence?--A pharmaco-EEG study.

PubMed

Zwierzyńska, Ewa; Andrzejczak, Dariusz; Pietrzak, Bogusława

2016-01-12

New antiepileptic drugs have been investigated for their potential role in the treatment of alcohol dependence. One of these drugs is retigabine and this study examines the effect of retigabine co-administered with ethanol on the development of alcohol dependence and the course of acute withdrawal syndrome. A pharmaco-EEG method was used to examine this impact in selected brain structures of rabbits (midbrain reticular formation, hippocampus and frontal cortex). Retigabine was administered p.o. at a dose of 5mg/kg/day with ethanol ad libitum for 6 weeks and then alone for 2 weeks during an abstinence period. Changes in bioelectric activity, which demonstrated the inhibitory effect of alcohol on the brain structures, were already visible after 2 weeks of ethanol administration. In the abstinence period, changes were of a different nature and significant neuronal hyperactivity was observed, particularly in the midbrain reticular formation and the hippocampus. This findings reveal that retigabine decreased ethanol-induced changes during both alcohol administration and abstinence periods. In particular, the modulatory effect of retigabine on the hippocampus may be a significant element of its mechanism of action in alcohol dependence therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function.

PubMed

Lundgaard, Iben; Wang, Wei; Eberhardt, Allison; Vinitsky, Hanna Sophia; Reeves, Benjamin Cameron; Peng, Sisi; Lou, Nanhong; Hussain, Rashad; Nedergaard, Maiken

2018-02-02

Prolonged intake of excessive amounts of ethanol is known to have adverse effects on the central nervous system (CNS). Here we investigated the effects of acute and chronic ethanol exposure and withdrawal from chronic ethanol exposure on glymphatic function, which is a brain-wide metabolite clearance system connected to the peripheral lymphatic system. Acute and chronic exposure to 1.5 g/kg (binge level) ethanol dramatically suppressed glymphatic function in awake mice. Chronic exposure to 1.5 g/kg ethanol increased GFAP expression and induced mislocation of the astrocyte-specific water channel aquaporin 4 (AQP4), but decreased the levels of several cytokines. Surprisingly, glymphatic function increased in mice treated with 0.5 g/kg (low dose) ethanol following acute exposure, as well as after one month of chronic exposure. Low doses of chronic ethanol intake were associated with a significant decrease in GFAP expression, with little change in the cytokine profile compared with the saline group. These observations suggest that ethanol has a J-shaped effect on the glymphatic system whereby low doses of ethanol increase glymphatic function. Conversely, chronic 1.5 g/kg ethanol intake induced reactive gliosis and perturbed glymphatic function, which possibly may contribute to the higher risk of dementia observed in heavy drinkers.

ADH1B polymorphism, alcohol consumption, and binge drinking in Slavic Caucasians: results from the Czech HAPIEE study.

PubMed

Hubacek, Jaroslav A; Pikhart, Hynek; Peasey, Anne; Kubinova, Ruzena; Bobak, Martin

2012-05-01

Several genetic polymorphisms influence the risk of heavy alcohol consumption but it is not well understood whether the genetic effects are similar in different populations and drinking cultures, nor whether the genetic influences on binge drinking are similar to those seen for alcoholism. We have analyzed the effect of the Arg47His (rs1229984) variant within the alcohol dehydrogenase (ADH1B) gene on a range of drinking related variables in a large Eastern European Slavic population (Czech HAPIEE study), which recruited random samples of men and women aged 45-69 years in 7 Czech towns (3,016 males and 3,481 females with complete data). Drinking frequency, annual alcohol intake, prevalence of binge drinking (≥100 g in men and ≥60 g in women at least once a month) and the mean dose of alcohol per occasion were measured by the graduated frequency questionnaire. Alcohol intake in a typical week was used to define heavy drinking (≥350 g/wk in men and ≥210 g in women). Problem drinking (≥2 positive answers on CAGE) and negative consequences of drinking on different aspects of life were also measured. The frequency of the His47 allele carriers was 11%. Homozygotes in the common allele (Arg47Arg), among both males and females, had significantly higher drinking frequency, and annual and weekly intake of alcohol than His47 carriers. The odds ratio of heavy drinking in Arg47Arg homozygotes versus His47 carriers was 2.1 (95% confidence intervals 1.1-3.2) in men and 2.2 (1.0-4.7) in women. In females, but not in males, Arg47Arg homozygotes had marginally significantly higher prevalence of binge drinking and mean alcohol dose per drinking session. There was no consistent association with problem drinking and negative consequences of drinking. The ADH1B genotype was associated with the frequency and volume of drinking but its associations with binge drinking and problem drinking were less consistent. Copyright © 2011 by the Research Society on Alcoholism.

Effect of prenatal ethanol exposure on sexual motivation in adult rats.

PubMed

Ávila, Mara Aparecida P; Marthos, Gabriela Cristina P; Oliveira, Liliane Gibram M; Figueiredo, Eduardo Costa; Giusti-Paiva, Alexandre; Vilela, Fabiana Cardoso

2016-08-01

Maternal alcohol use during pregnancy adversely affects prenatal and postnatal growth and increases the risk of behavioral deficits. The aim of the present study was to evaluate the effect of prenatal exposure to a moderate dose of alcohol on sexual motivation during adulthood. Rats were prenatally exposed to ethanol by feeding pregnant dams a liquid diet containing 25% ethanol-derived calories on days 6 through 19 of gestation. The controls consisted of pair-fed dams (receiving an isocaloric liquid diet containing 0% ethanol-derived calories) and dams with ad libitum access to a liquid control diet. The sexual motivation of offspring was evaluated during adulthood. The results revealed that the male and female pups of dams treated with alcohol exhibited reduced weight gain, which persisted until adulthood. Both male and female adult animals from dams that were exposed to alcohol showed a reduction in the preference score in the sexual motivation test. Taken together, these results provide evidence of the damaging effects of prenatal alcohol exposure on sexual motivation responses in adulthood. Copyright © 2016 Elsevier Inc. All rights reserved.

mGluR5 antagonist MPEP reduces ethanol-seeking and relapse behavior.

PubMed

Bäckström, Pia; Bachteler, Daniel; Koch, Sabrina; Hyytiä, Petri; Spanagel, Rainer

2004-05-01

The glutamatergic system plays an important role in mediating neurobehavioral effects of ethanol. Metabotropic glutamate receptors subtype 5 (mGluR5) are modulators of glutamatergic neurotransmission and are abundant in brain regions known to be involved in ethanol self-administration. Here, we studied the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a highly potent, noncompetitive mGlu5 receptor antagonist, on voluntary ethanol consumption and relapse behavior. For this purpose, we used two models for the measurement of relapse behavior: (i) reinstatement of ethanol-seeking behavior by drug-associated cues and (ii) the alcohol deprivation effect in long-term ethanol-consuming rats. In the first set of experiments, rats were trained to lever press for ethanol in the presence of a distinct set of cues. After extinction, the animals were exposed to the respective cues that initiated reinstatement of responding. A response-contingent ethanol prime further enhanced responding compared to the conditioned cues alone. Under these conditions, MPEP (0, 1, 3, and 10 mg/kg) attenuated ethanol seeking significantly and in a dose-related manner. However, at the highest dose, MPEP also decreased the number of inactive lever responses. In the second set of experiments, rats with 1 year of ethanol experience and repeated deprivation phases were used. A subchronic treatment with MPEP (twice daily; 0, 3, and 10 mg/kg) resulted in a significant and dose-dependent reduction of the alcohol deprivation effect (ADE). Although the same MPEP treatment regimen decreased baseline drinking, this effect was not as pronounced as on the ADE. These results show in two commonly used models of relapse to ethanol that pharmacological targeting of mGlu5 receptors may be a promising approach for the treatment of alcoholism.

Marine collagen peptides protect against early alcoholic liver injury in rats.

PubMed

Lin, Bing; Zhang, Feng; Yu, Yongchao; Jiang, Qinghao; Zhang, Zhaofeng; Wang, Junbo; Li, Yong

2012-04-01

Marine collagen peptides (MCP) have been reported to exhibit antioxidative activity, which is the common property of numerous hepatoprotective agents. Previous studies have shown that MCP have biological functions including anti-hypertension, anti-ulcer, anti-skin ageing and extending the life span. However, its role in alcoholic liver injury remains unknown. The present study aimed to investigate the effects of MCP on early alcoholic liver injury in rats. Rats were administered with alcohol at a dose of 6 g/kg body weight intragastrically per d to induce early liver injury, which was then evaluated by serum markers and histopathological examination. Treatment with MCP could reverse the increased level of serum aminotransferase and reduce hepatic histological damage. In addition, MCP attenuated the alteration in serum superoxide dismutase and malondialdehyde levels. MCP also counteracted the increased levels of total cholesterol and TAG. However, no significant difference was observed in the contents of alcohol dehydrogenase both in liver and serum protein of rats. These findings suggest that MCP have a protective effect on early alcoholic liver injury in rats by their antioxidative activity and improving lipid metabolism.

Effects of ethanol on cocaine self-administration in monkeys responding under a second-order schedule of reinforcement.

PubMed

John, William S; Nader, Michael A

2017-01-01

Concurrent alcohol use among cocaine abusers is common but the behavioral variables that promote co-abuse are not well understood. The present study examined the effects of intragastric (i.g.) ethanol (EtOH) administration in monkeys responding under a schedule of cocaine reinforcement in which extensive drug seeking was maintained by conditioned stimuli. Four adult male cynomolgus monkeys (Macaca fascicularis) were trained to respond under a second-order fixed-interval (FI) 600s (fixed-ratio (FR) 30:S) schedule of cocaine (0.003-0.56mg/kg/injection) presentation. Sessions ended after 5 injections or 90min had elapsed. Different EtOH doses (0.5-2.0g/kg, i.g.) were administered 30min before the session, typically on Tuesdays and Fridays. Blood ethanol concentrations (BECs) were also assessed. Pattern of FI responding was assessed by determining quarter-life (QL) values. Cocaine self-administration was characterized as an inverted U-shaped function of dose; QL values increased monotonically with dose. EtOH pretreatments dose-dependently decreased self-administration at several cocaine doses in 3 of 4 monkeys. In one animal, EtOH increased low-dose cocaine-maintained responding. For all monkeys, QL values were increased by EtOH when low- and high-cocaine doses were self-administered, suggesting additive effects of EtOH and cocaine. Furthermore, BECs were not altered following cocaine self-administration. The reductions in cocaine self-administration and the increases in QL values following EtOH, suggest that EtOH was enhancing cocaine-related conditioned reinforcement. A better understanding of the behavioral mechanisms that mediate the co-abuse of alcohol and cocaine will lead to improved treatments for both drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Molecular weight distribution of organic matter by ozonation and biofiltration.

PubMed

Lin, Yen-Hui

2012-01-01

Molecular weight (MW) distribution of organic matter by ozonation and biofiltration was evaluated using gel chromatography. The MW distribution of organic matter by Sephadex G-25 was observed from groups 2 (MW = 1,029-7,031 g/mol) and 3 (MW = 303-1,029 g/mol) shifted to groups 2, 3 and 4 (MW < 303 g/mol) under ozone doses of 0.1 and 0.4 mg O₃/mg total organic carbon (TOC). The shift in MW increases as ozone dosage increases. Biofiltration effectively degraded the organic molecule of group 2; however, the biofiltration only slightly degraded the organic molecule of group 4. Increased ozone dose destroyed functional groups C═C in phenolic and C-O in alcoholic compounds and increased UV-insensitive biodegradable organic carbon for subsequent biofiltration. Biofiltration effectively degraded organic compounds of alcohols and alkenes at an ozone dose of 0.1 mg O₃/mg TOC. Experimental approaches in this study can be applied to evaluate and diagnose the function of a full-scale process combining ozonation and biofiltration in drinking water treatment plants.

Anxiolytic effects of buspirone and MTEP in the Porsolt Forced Swim Test.

PubMed

Lee, Kaziya M; Coelho, Michal A; Sern, Kimberly R; Class, MacKayla A; Bocz, Mark D; Szumlinski, Karen K

2017-01-01

Traditionally, a reduction in floating behavior or immobility in the Porsolt forced swim test (FST) is employed as a predictor of antidepressant efficacy. However, over the past several years, our studies of alcohol withdrawal-induced negative affect consistently indicate the coincidence of increased anxiety-related behaviors on various behavioral tests with reduced immobility in the FST. Further, this behavioral profile correlates with increased mGlu5 protein expression within limbic brain regions. As the role for mGlu5 in anxiety is well established, we hypothesized that the reduced immobility exhibited by alcohol-withdrawn mice when tested in the FST might reflect anxiety, possibly a hyper-reactivity to the acute swim stressor. Herein, we evaluated whether or not the decreased FST immobility during alcohol withdrawal responds to systemic treatment with a behaviorally-effective dose of the prototypical anxiolytic, buspirone (5 mg/kg). We also determined the functional relevance of the withdrawal-induced increase in mGlu5 expression for FST behavior by comparing the effects of buspirone to a behaviorally effective dose of the mGlu5 negative allosteric modulator MTEP (3 mg/kg). Adult male C57BL/6J mice were subjected to a 14-day, multi-bottle, binge-drinking protocol that elicits hyper-anxiety and increases glutamate-related protein expression during early withdrawal. Control animals received only water. At 24hr withdrawal, animals from each drinking condition were subdivided into groups and treated with an IP injection of buspirone, MTEP, or vehicle, 30min prior to the FST. Drug effects on general locomotor activity were also assessed. As we reported previously, alcohol-withdrawn animals exhibited significantly reduced immobility in the FST compared to water controls. Both buspirone and MTEP significantly increased immobility in alcohol-withdrawn animals, with a modest increase also seen in water controls. No significant group differences were observed for locomotor activity, indicating that neither anxiolytic was sedating. These results provide predictive validity for increased swimming/reduced immobility in the FST as a model of anxiety and provide novel evidence in favor of mGlu5 inhibition as an effective therapeutic strategy for treating hyperanxiety during alcohol withdrawal.

THE EFFECT OF $gamma$-IRRADIATION ON ALCOHOLIC BEVERAGES AND ITS POTENTIALITY FOR PRACTICAL APLICATION (in Japanese)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okazawa, Y.; Namiki, M.; Iida, S.

Generally, changes in flavor and taste of alcoholic beverages caused by irradiation of Co/sub gamma / rays are remarkable. In the case of Sake (Japanese rice wine), artificial Sake, and wines, occurrence of off-flavor and deterioration in qualities are unavoidable when they are irradiated more than about 5 x 10/sup 4/ r. However, maturing of taste and improvement of qualities by irradiation of relatively lower doses are found. The suitabie dose range for maturing effect depends on the condition of materials exposed to irradiation, and in order to prevent off-flavor development, substitution of gas phase during irradiation seems to bemore » effective. Similar maturing effects are obtained with many distilled liquors. The maturities are markediy promoted with doses of 1 x 10/sup 5/ to 3 x 10/sup 5/ r. As doses become greater, losses of characteristic original flavor and stimulative tastes are observed. Radiation effects are able to improve qualities of Sho-chu spirits (distillates of ferment mashes prepared from rice and sweet potato). The changes of whiskies and brandies caused by gamma irradiation, immediately after distillation and before storage, are of interest. Flavor change is similar to that occurring in the eariy period of storage in barrels, and the maturity is equal to that of beverages stored several years. Chemical analysis of components and measurements of physical properties are carried out in relation with the changes in flavors and taste. (JAIF)« less

Problem drinking and low-dose naltrexone-assisted opioid detoxification.

PubMed

Mannelli, Paolo; Peindl, Kathleen; Patkar, Ashwin A; Wu, Li-Tzy; Tharwani, Haresh M; Gorelick, David A

2011-05-01

The influence of alcohol use on opioid dependence is a major problem that warrants a search for more effective treatment strategies. The addition of very-low-dose naltrexone (VLNTX) to methadone taper was recently associated with reduced withdrawal intensity during detoxification. In a secondary analysis of these data, we sought to determine whether problem drinking affects detoxification outcomes and whether symptoms are influenced by VLNTX use. Opioid-dependent patients (N = 174) received naltrexone (0.125 or 0.250 mg/day) or placebo in a double-blind, randomized design during methadone-based, 6-day inpatient detoxification. Alcohol consumption was assessed at admission using the Addiction Severity Index and selfreport. Outcome measures were opioid withdrawal intensity, craving, and retention in treatment. Problem drinking-opioid dependent patients (n = 79) showed episodic heavy alcohol use and reported increased subjective opioid withdrawal intensity (p = .001), craving (p = .001), and significantly lower rate of retention in treatment (p = .02). Individuals with problem drinking and opioid dependence who were treated with VLNTX (n = 55) showed reduced withdrawal (p = .05) and a lower rate of treatment discontinuation (p = .03), resuming alcohol intake in smaller numbers the day following discharge (p = .03). Treatment effects were more pronounced on anxiety, perspiration, shakiness, nausea, stomach cramps, and craving. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Heavy drinking is associated with worse opioid detoxification outcomes. The addition of VLNTX is safe and is associated with reduced withdrawal symptoms and better completion rate in these patients. Further studies should explore the use of VLNTX in detoxification and long-term treatment of combined alcohol-opioid dependence and alcohol dependence alone.

Topiramate in the treatment of substance-related disorders: a critical review of the literature.

PubMed

Shinn, Ann K; Greenfield, Shelly F

2010-05-01

To critically review the literature on topiramate in the treatment of substance-related disorders. A PubMed search of human studies published in English through January 2009 was conducted using the following search terms: topiramate and substance abuse, topiramate and substance dependence, topiramate and withdrawal, topiramate and alcohol, topiramate and nicotine, topiramate and cocaine, topiramate and opiates, and topiramate and benzodiazepines. 26 articles were identified and reviewed; these studies examined topiramate in disorders related to alcohol, nicotine, cocaine, methamphetamine, opioids, Ecstasy, and benzodiazepines. Study design, sample size, topiramate dose and duration, and study outcomes were reviewed. There is compelling evidence for the efficacy of topiramate in the treatment of alcohol dependence. Two trials show trends for topiramate's superiority over oral naltrexone in alcohol dependence, while 1 trial suggests topiramate is inferior to disulfiram. Despite suggestive animal models, evidence for topiramate in treating alcohol withdrawal in humans is slim. Studies of topiramate in nicotine dependence show mixed results. Human laboratory studies that used acute topiramate dosing show that topiramate actually enhances the pleasurable effects of both nicotine and methamphetamine. Evidence for topiramate in the treatment of cocaine dependence is promising, but limited by small sample size. The data on opioids, benzodiazepines, and Ecstasy are sparse. Topiramate is efficacious for the treatment of alcohol dependence, but side effects may limit widespread use. While topiramate's unique pharmacodynamic profile offers a promising theoretical rationale for use across multiple substance-related disorders, heterogeneity both across and within these disorders limits topiramate's broad applicability in treating substance-related disorders. Recommendations for future research include exploration of genetic variants for more targeted pharmacotherapies. ©Copyright 2010 Physicians Postgraduate Press, Inc.

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice

PubMed Central

Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

2015-01-01

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure. PMID:25960751

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice.

PubMed

Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

2015-01-01

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure.

Cannabis effects on driving lateral control with and without alcohol.

PubMed

Hartman, Rebecca L; Brown, Timothy L; Milavetz, Gary; Spurgin, Andrew; Pierce, Russell S; Gorelick, David A; Gaffney, Gary; Huestis, Marilyn A

2015-09-01

Effects of cannabis, the most commonly encountered non-alcohol drug in driving under the influence cases, are heavily debated. We aim to determine how blood Δ(9)-tetrahydrocannabinol (THC) concentrations relate to driving impairment, with and without alcohol. Current occasional (≥1×/last 3 months, ≤3days/week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500mg placebo, low (2.9%)-THC, or high (6.7%)-THC vaporized cannabis over 10min ad libitum in separate sessions (within-subject design, 6 conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives (∼0.8h duration). Blood, oral fluid (OF), and breath alcohol samples were collected before (0.17h, 0.42h) and after (1.4h, 2.3h) driving that occurred 0.5-1.3h after inhalation. We evaluated standard deviations of lateral position (lane weave, SDLP) and steering angle, lane departures/min, and maximum lateral acceleration. In N=18 completers (13 men, ages 21-37years), cannabis and alcohol increased SDLP. Blood THC concentrations of 8.2 and 13.1μg/L during driving increased SDLP similar to 0.05 and 0.08g/210L breath alcohol concentrations, the most common legal alcohol limits. Cannabis-alcohol SDLP effects were additive rather than synergistic, with 5μg/L THC+0.05g/210L alcohol showing similar SDLP to 0.08g/210L alcohol alone. Only alcohol increased lateral acceleration and the less-sensitive lane departures/min parameters. OF effectively documented cannabis exposure, although with greater THC concentration variability than paired blood samples. SDLP was a sensitive cannabis-related lateral control impairment measure. During drive blood THC ≥8.2μg/L increased SDLP similar to notably-impairing alcohol concentrations. Despite OF's screening value, OF variability poses challenges in concentration-based effects interpretation. Published by Elsevier Ireland Ltd.

Baclofen effects on alcohol seeking, self-administration and extinction of seeking responses in a within-session design in baboons

PubMed Central

Duke, Angela N.; Kaminski, Barbara J.; Weerts, Elise M.

2012-01-01

Baclofen, a GABAB receptor agonist, is currently under investigation as a potential treatment to prevent relapse to drinking in alcohol dependent persons. In the current study, two groups of baboons were trained under a chained schedule of reinforcement (CSR), with 3 linked components, which were each correlated with different response requirements and cues. Fulfilling the requirement in the 2nd link initiated the 3rd link where either alcohol (n=4) or a preferred non-alcoholic beverage (Tang, n=5) was available for self-administration; failure to complete the response requirement in Link 2 ended the session (no access to alcohol or Tang). Seeking responses in Link 2 were used as indices of the motivational processes thought to be involved in relapse. The effects of baclofen (0.1 – 2.4 mg/kg) were examined under conditions with alcohol or Tang access and under extinction. Under the CSR baclofen (1.8 and 2.4 mg/kg) significantly decreased (p<0.05) alcohol self-administration responses and total g/kg alcohol intake. In contrast, only the highest dose of baclofen (2.4 mg/kg) reduced Tang self-administration and consumption. Under within-session extinction conditions, baclofen (1.8 and 2.4 mg/kg) facilitated extinction of responding for both alcohol and Tang, particularly during the first 10 min of extinction. Baclofen may be effective in reducing craving and alcohol drinking, although the facilitation of extinction and suppression of both alcohol and Tang self-administration by baclofen suggests these effects may be related to a more general suppression of consummatory and conditioned behaviors. PMID:22458648

Baclofen effects on alcohol seeking, self-administration and extinction of seeking responses in a within-session design in baboons.

PubMed

Duke, Angela N; Kaminski, Barbara J; Weerts, Elise M

2014-01-01

Baclofen, a gamma-aminobutyric acidB receptor agonist, is currently under investigation as a potential treatment to prevent relapse to drinking in alcohol-dependent persons. In the current study, two groups of baboons were trained under a chained schedule of reinforcement (CSR), with three linked components, which were each correlated with different response requirements and cues. Fulfilling the requirement in the second link initiated the third link where either alcohol (n = 4) or a preferred non-alcoholic beverage (Tang, n = 5) was available for self-administration; failure to complete the response requirement in Link 2 ended the session (no access to alcohol or Tang). Seeking responses in Link 2 were used as indices of the motivational processes thought to be involved in relapse. The effects of baclofen (0.1-2.4 mg/kg) were examined under conditions with alcohol or Tang access and under extinction. Under the CSR, baclofen (1.8 and 2.4 mg/kg) significantly decreased (P < 0.05) alcohol self-administration responses and total g/kg alcohol intake. In contrast, only the highest dose of baclofen (2.4 mg/kg) reduced Tang self-administration and consumption. Under within-session extinction conditions, baclofen (1.8 and 2.4 mg/kg) facilitated extinction of responding for both alcohol and Tang, particularly during the first 10 minutes of extinction. Baclofen may be effective in reducing craving and alcohol drinking, although the facilitation of extinction and suppression of both alcohol and Tang self-administration by baclofen suggests these effects may be related to a more general suppression of consummatory and conditioned behaviors. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

Simian Immunodeficiency Virus Infection Increases Blood Ethanol Concentration Duration After Both Acute and Chronic Administration.

PubMed

Simon, Liz; Siggins, Robert; Winsauer, Peter; Brashear, Meghan; Ferguson, Tekeda; Mercante, Don; Song, Kejing; Vande Stouwe, Curtis; Nelson, Steve; Bagby, Gregory; Amedee, Angela; Molina, Patricia E

2018-02-01

Alcohol use disorder (AUD) is a frequent comorbidity among people living with HIV/AIDS (PLWHA). Alcohol consumption is a significant predictor of nonadherence to antiretroviral therapy (ART), as well as worsening immunological and virological indicators among PLWHA. Clinical studies indicate that higher viral loads increase sensitivity to alcohol in PLWHA. The factors that influence alcohol kinetics after HIV infection and initiation of ART are not well understood, limiting the information upon which interventions can be designed to ameliorate the impact of alcohol misuse on this vulnerable patient population. To better understand the relationship between viral load and alcohol kinetics, we measured changes in doses of intragastric ethanol administration to achieve target blood ethanol concentration (BEC) in a rhesus macaque model of chronic binge alcohol (CBA) administration and acute changes following a single acute binge dose of alcohol (ABA) pre- and post-simian immunodeficiency virus (SIV) infection, and following ART initiation. Our results from CBA (14 months)-administered SIV-infected male macaques showed that, following ART initiation, macaques required higher doses of alcohol to achieve a target peak BEC compared with non-ART-treated SIV-infected macaques. In animals given ABA, we found prolonged duration of elevated BEC and decreased elimination rate of alcohol that was not corrected following 7 weeks of ART. These findings suggest that binge drinking associated with AUD could negatively interact with HIV infection and enhance disease progression. These findings further support the need for implementation of behavioral or therapeutic interventions to decrease alcohol consumption to improve the quality of life in PLWHA.

[The safety and efficacy of alimemazine (teraligen) in relieving anxiety in patients with alcohol addiction].

PubMed

Asadullin, A R; Yuldashev, V L; Asadullina, G M; Akhmetova, E A; Ishchenko, K A

2018-01-01

To assess the efficacy of monotherapy of anxiety in alcoholism with alimemazine (teraligen). Thirty-six patients with alcohol addiction were treated with alimemazine in dose 15 mg during 9 month. In control group (11 patients) teraligen was no used. A significant positive effect of treatment with teraligen was observed. There were the improvement in alcohol addiction course, decrease in scores on the Addiction Severity Index (ASI) from severe to mild level and decrease in trait and state anxiety measured with the Spielberger-Khanin scale from high to low levels. The reduction on symptoms of depression from moderate (at baseline) to subdepressive levels on the Beck Depression Inventory was noted in the end of treatment.

Alcoholic Beverage Consumption and Chronic Diseases

PubMed Central

Zhou, Yue; Zheng, Jie; Li, Sha; Zhou, Tong; Zhang, Pei; Li, Hua-Bin

2016-01-01

Epidemiological and experimental studies have consistently linked alcoholic beverage consumption with the development of several chronic disorders, such as cancer, cardiovascular diseases, diabetes mellitus and obesity. The impact of drinking is usually dose-dependent, and light to moderate drinking tends to lower risks of certain diseases, while heavy drinking tends to increase the risks. Besides, other factors such as drinking frequency, genetic susceptibility, smoking, diet, and hormone status can modify the association. The amount of ethanol in alcoholic beverages is the determining factor in most cases, and beverage types could also make an influence. This review summarizes recent studies on alcoholic beverage consumption and several chronic diseases, trying to assess the effects of different drinking patterns, beverage types, interaction with other risk factors, and provide mechanistic explanations. PMID:27231920

When does alcohol hurt? A driving simulator study.

PubMed

Vollrath, Mark; Fischer, Josefine

2017-12-01

World-wide, alcohol is still a major cause of traffic accidents. The dose-related accident risk function has been found in a large number of risk studies. A plethora of laboratory studies has examined the effect of alcohol with regard to different information processing capabilities of drivers. Summarizing the results, alcohol effects occur at lower blood alcohol concentrations (BAC) the more complex the tasks get. However, in contrast, typical alcohol-related crashes are frequently single vehicle crashes but not so often crashes in complex situations like at intersections. It may be that the subjective assessment of the traffic situation and the adaptation of behavior under the influence of alcohol plays a major role in accident causation. In order to examine this hypothesis, two driving simulator studies were conducted at a target BAC of 0.5g/l comparing two (alcohol vs. placebo; n=48, Experiment 1) and three (sober, placebo and alcohol; n=63, Experiment 2) groups of subjects in two critical scenarios. The first scenario was a seemingly easy traffic situation and was supposed to lead to a relaxed driving behavior under alcohol. The second scenario involved a complex intersection situation where especially drivers under the influence of alcohol should try to concentrate and compensate their experienced alcohol effects. In all scenarios, a critical object appeared suddenly and the driver had to react fast in order to prevent a (simulated) accident. Overall, the results support the hypothesis. Accidents were more frequent for alcohol drivers as compared to placebo/sober drivers in the easy scenario, but not the complex one. The initial speed of the driver when entering the scenario seems to play a major role in the accident causation. Drivers under the influence of alcohol seem to lower their speed in complex scenarios, possibly to thus counteract alcohol effects. In seemingly easy scenarios this does not seem necessary for them and the arousing effect of alcohol may contribute to driving faster. The results are summarized in a model of alcohol-related crashes. Further in-depth analyses of real crashes would be an interesting next step to further corroborate this model. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biochemical Effects of Energy Drinks Alone or in Combination with Alcohol in Normal Albino Rats

PubMed Central

2014-01-01

Purpose: To determine the biochemical effects of energy drink alone or in combination with alcohol in normal albino rats. Methods: Twenty male albino rats weighing 160-180g were assigned into groups A-E of four rats per group. Group A and B rats were given low and high doses of ED, respectively, groups C and D were administered low and high doses of EDmA, respectively while group E rats were given distilled water and served as control. The treatment lasted for 30 days after which the animals were killed and their blood collected for laboratory analyses using standard methods. Results: There were no significant differences in body weight, packed cell volume and haemoglobin concentration with either administration of ED or EDmA in comparison to the control. Energy drink alone or EDmA has significant effects on total white blood cell count, plasma potassium, calcium, renal functions, liver enzymes and plasma triglycerides, with EDmA having more effects than ED alone, except for body weight where the energy drink alone has higher effect. Conclusion: Consumption of energy drink alone or in combination with alcohol is associated with significant alterations in some biochemical parameters. Caution should be exercised while consuming either of them. Public health education is urgently needed to correct the wrong impression already formed by the unsuspecting consumers, especially the youths. PMID:24409412

Caffeine antagonism of alcohol-induced driving impairment.

PubMed

Liguori, A; Robinson, J H

2001-07-01

The extent to which caffeine antagonizes alcohol-induced impairment of simulated automobile driving at the current lowest legal American limit (0.08% BrAC) was the focus of this study. Fifteen adults swallowed a capsule (0, 200, or 400 mg caffeine) then drank a beverage (0.0 or 0.6 g/kg ethanol) in a within-subject, double-blind, randomized procedure. Forty-five minutes later, participants completed a test battery of subjective effects scales, dynamic posturography, critical flicker fusion (CFF), choice reaction time (CRT), divided attention (Stroop test), and simulated driving. Alcohol alone increased ratings of 'dizzy', 'drug effect', and 'high', slowed CRT and brake latency, and increased body sway. Caffeine alone increased ratings of 'alert' and 'jittery', but did not significantly affect body sway or psychomotor performance. Both caffeine doses comparably counteracted alcohol impairment of brake latency but not CRT or body sway. Brake latency with either alcohol-caffeine combination remained significantly longer than that with placebo. Stroop and CFF performance were unaffected by any drug condition. The results suggest that caffeine may increase alertness and improve reaction time after alcohol use but will not completely counteract alcohol impairment in a driver.

Oxytocin Reduces Ethanol Self-Administration in Mice

PubMed Central

King, Courtney E.; Griffin, William C.; Luderman, Lauryn N.; Kates, Malcolm M.; McGinty, Jacqueline F.; Becker, Howard C.

2017-01-01

Background Excessive ethanol consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces ethanol consumption. Methods Male C57BL/6J mice were given access to ethanol (20% v/v) using a model of binge-like drinking (“drinking-in-the-dark”) that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, ethanol (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive- ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models. Results Oxytocin (0, 0.3, 1, 3 or 10mg/kg) dose-dependently reduced ethanol consumption (maximal 45% reducton) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin’s effect was blocked by pretreatment with an oxytocin receptor antagonist and the pattern of contacts (licks) at the ethanol bottle suggested a reduction in motivation to drink ethanol. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for ethanol and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for ethanol at doses that did not alter responding for sucrose. Discussion These results indicate that oxytocin reduces ethanol consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for ethanol at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Neverthess, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder. PMID:28212464

Does Timing of Alcohol Administration Affect Sleep?

PubMed Central

Van Reen, Eliza; Tarokh, Leila; Rupp, Tracy L.; Seifer, Ron; Carskadon, Mary A.

2011-01-01

Study Objectives: To explore the time of day effects of alcohol on sleep, we examined sleep following alcohol administered at four times of day and three homeostatic loads during a 20-hr forced desynchrony (FD) protocol. Participants: Twenty-six healthy young adults (21–25 yrs) were studied. Design: Participants were dosed at 4 clock times: 0400 (n = 6; 2 females), 1600 (n = 7; 4 females), 1000 (n = 6; 1 female) or 2200 (n = 7; 2 females). Participants slept 2300 to 0800 for at least 12 nights before the in-lab FD study. Double blind placebo and alcohol (vodka tonic targeting 0.05g% concentration) beverages were each administered three times during FD at different homeostatic loads: low (4.25 or 2.24 hrs awake), medium (8.25 or 6.25 hrs awake), high (12.25 or 10.25 hrs awake) in the 0400 and 1600 or 1000 and 2200 groups, respectively. Sleep was staged and subjected to spectral analysis. Measurements and Results: Breath Alcohol Concentration (BrAC) confirmed targeted maximal levels. At bedtime, BrAC was 0 in the low and medium homeostatic load conditions; however, at high homeostatic load, BrAC was still measurable. Spectral characteristics of sleep were unaffected with alcohol at any time of day. Few alcohol related changes were seen for sleep stages; however, with alcohol given at 0400 at a high homeostatic load there was an increase in wake. Conclusions: These data lend support to the idea that alcohol may be disruptive to sleep; however, our findings are inconsistent with the idea that a low dose of alcohol is a useful sleep aid when attempting to sleep at an adverse circadian phase. Citation: Van Reen E; Tarokh L; Rupp TL; Seifer R; Carskadon MA. Does timing of alcohol administration affect sleep? SLEEP 2011;34(2):195-205. PMID:21286495

Virgin coconut oil extract mitigates testicular-induced toxicity of alcohol use in antiretroviral therapy.

PubMed

Ogedengbe, O O; Naidu, E C S; Akang, E N; Offor, U; Onanuga, I O; Peter, A I; Jegede, A I; Azu, O O

2018-04-14

The consumption of alcohol by people living with HIV/AIDS is associated with a graver prognosis. Long-term use of antiretrovirals may have certain health challenges that may be aggravated by concomitant alcohol use. This study investigated virgin coconut oil (VCO) as an adjuvant to the deleterious effects of highly active antiretroviral therapy (HAART) and alcohol on the cyto-architecture and functioning of the testis. Forty adult male Sprague-Dawley rats, weighing 165~176 g, were divided into eight groups and treated according to protocol. Testicular histology, stereological parameters, seminal fluid, testosterone, luteinizing hormone, follicle-stimulating hormone, the antioxidants marker malondialdehyde (MDA), and antioxidant glutathione (GSH) were examined. The use of ethanol alone and ethanol + HAART showed extensive degeneration in the seminiferous epithelium, decreased semen quality, disorganized basement membrane and widened, hypocellular interstitium. GSH was significantly decreased in the ethanol alone treated group with no significant effect on testosterone, LH, and MDA levels. Adjuvant treatment with VCO at low dose (2.5 mL/kg/bw) improved sperm motility with a partial restoration of the histopathological alterations. High doses of VCO (5.0 mL/kg/bw) showed greater improvement with respect to sperm counts, increased FSH hormonal and GSH antioxidant levels, and a well-preserved testicular cyto-architecture. © 2018 American Society of Andrology and European Academy of Andrology.

Behavioral Impulsivity Does Not Predict Naturalistic Alcohol Consumption or Treatment Outcomes

PubMed Central

Mullen, Jillian; Mathias, Charles W.; Karns, Tara E.; Liang, Yuanyuan; Hill-Kapturczak, Nathalie; Roache, John D.; Lamb, Richard J.; Dougherty, Donald M.

2016-01-01

Objective The purpose of this study was to determine if behavioral impulsivity under multiple conditions (baseline, after alcohol consumption or after serotonin depletion) predicted naturalistic alcohol use or treatment outcomes from a moderation-based contingency management intervention. Method The current data analysis pulls information from three phases of a large study: 1) Phase 1 examined baseline and the effects of alcohol use and serotonin depletion on three types of behavioral impulsivity: response initiation (IMT task), response inhibition (GoStop task), and delay discounting (SKIP task); 2) Phase 2 involved 28 days of naturalistic drinking; and 3) Phase 3 involved 3 months of contingency management. During phases 2 and 3 alcohol use was measured objectively using transdermal alcohol monitors. The results of each individual phase has been previously published showing that at a group level the effects of alcohol consumption on impulsivity were dependent on the component of impulsivity being measured and the dose of alcohol consumed but serotonin depletion had no effect on impulsivity, and that a moderation-based contingency management intervention reduced heavy drinking. Results The current analysis combining data from those who completed all three phases (n = 67) showed that impulsivity measured at baseline, after alcohol consumption, or after serotonin depletion did not predict naturalistic drinking or treatment outcomes from a moderation-based CM treatment. Conclusions Contingency management interventions may prove to be an effective intervention for impulsive individuals, however, normal variations in measured impulsivity do not seem to relate to normal variations in drinking pattern or response to moderation-based contingency management. PMID:27746702

The nociceptin/orphanin FQ receptor agonist Ro 64-6198 reduces alcohol self-administration and prevents relapse-like alcohol drinking.

PubMed

Kuzmin, Alexander; Kreek, Mary Jeanne; Bakalkin, Georgy; Liljequist, Sture

2007-04-01

Effects of the opioid receptor like-1 (ORL-1) receptor agonist Ro 64-6198 (0.1, 0.3, and 1.0 mg/kg intraperitoneally (i.p.)) on operant ethanol self-administration and activation of self-administration by ethanol deprivation were studied in male Wistar rats. Acute administration of Ro 64-6198 caused a dose-dependent reduction of ethanol self-administration. In comparison, the opioid antagonist naltrexone (0.1, 0.3, and 1.0 mg/kg i.p.) inhibited ethanol self-administration at all doses tested. Ethanol deprivation for 10 days significantly increased ethanol self-administration during the first 2 days after deprivation. Daily pretreatment with Ro 64-6198 (0.3 mg/kg) or naltrexone (0.3 mg/kg) during the last 3 days of ethanol deprivation abolished the deprivation-induced increase in ethanol intake. Thus, stimulation of the ORL-1 receptors by Ro 64-6198 reduced the acute reinforcing effects of ethanol and prevented relapse-like behavior in the ethanol-deprivation model in a similar manner as a blockade of opioid receptors by naltrexone. Ro 64-6198 at 0.1 and 0.3 mg/kg doses did not alter self-administration of 0.2% saccharin solution, indicating an apparent selectivity of this compound in modification of ethanol reward. These findings add further support to the idea that Ro 64-6198 and potentially other synthetic ORL-1 receptor agonists are as effective as naltrexone in blocking the actions of ethanol important for its addictive potential in animal experiments, and therefore may have therapeutic value in the treatment of alcoholism.

A preliminary study of hepatitis B virus replication during short-term (7-day) social drinking.

PubMed

Novick, D M; Jenkins, W J; Karayiannis, P; Thomas, H C

1987-12-01

The purpose of this study is to determine the effect of short-term social drinking on hepatitis B virus (HBV) replication as measured by serum levels of hepatitis B virus DNA (HBV-DNA). We studied five male carriers of hepatitis B e antigen who were social drinkers. Levels of HBV-DNA, blood alcohol, and aspartate aminotransferase (AST) were measured during abstinence from alcohol, before and during a test dose (29.8 g) of alcohol which followed one week of abstinence, and before and during the same test dose which followed social drinking for one week. We observed no significant changes in HBV-DNA or AST levels. These data suggest that a single one-week period of social drinking in patients with chronic HBV infection does not cause enhanced viral replication. The risks of repeated ingestion of moderate amounts of alcohol by such patients have not been established. Interpretation of our data is limited by the small number of subjects, and further studies are needed. Nevertheless, our results are consistent with published recommendations that social drinking by nonalcoholic HBV carriers should be restricted but need not be totally forbidden.

The Peroxisome Proliferator-Activated Receptor Alpha Agonist Fenofibrate Attenuates Alcohol Self-administration in Rats

PubMed Central

Haile, Colin N.; Kosten, Therese A.

2017-01-01

Fibrates are a class of medications used to treat hypercholesterolemia and dyslipidemia that target nuclear peroxisome proliferator-activated receptors (PPARs). Studies have shown the PPARα agonist fenofibrate decreases voluntary EtOH consumption however its impact on the reinforcing and motivational effects of EtOH is unknown. We evaluated the ability of fenofibrate (25, 50 and 100mg/kg), to alter EtOH (10%, w/v) and sucrose (2%, w/v) operant self-administration in rats under a FR2 schedule of reinforcement over four days and under a progressive ratio (PR) schedule on day five of treatment. Results showed fenofibrate dose-dependently decreased EtOH self-administration under both schedules of reinforcement with the greatest effects seen after four to five days of treatment. Fenofibrate decreased responding for sucrose only under the PR schedule of reinforcement and this effect was not dose-dependent. These findings provide further evidence for fenofibrate as a potential treatment for alcohol use disorder in humans. PMID:28088358

Effect of electron beam radiation processing on mechanical and thermal properties of fully biodegradable crops straw/poly (vinyl alcohol) biocomposites

NASA Astrophysics Data System (ADS)

Guo, Dan

2017-01-01

Fully biodegradable biocomposites based on crops straw and poly(vinyl alcohol) was prepared through thermal processing, and the effect of electron beam radiation processing with N,N-methylene double acrylamide as radiation sensitizer on mechanical and thermal properties of the biocomposites were investigated. The results showed that, when the radiation dose were in the range of 0-50 kGy, the mechanical and thermal properties of the biocomposites could be improved significantly through the electron beam radiation processing, and the interface compatibility was also improved because of the formation of stable cross-linked network structure, when the radiation dose were above the optimal value (50 kGy), the comprehensive properties of the biocomposites were gradually destroyed. EB radiation processing could be used as an effective technology to improve the comprehensive performance of the biocomposites, and as a green and efficient processing technology, radiation processing takes place at room temperature, and no contamination and by-product are possible.

Disruptions in Functional Network Connectivity during Alcohol Intoxicated Driving

PubMed Central

Rzepecki-Smith, Catherine I.; Meda, Shashwath A.; Calhoun, Vince D.; Stevens, Michael C.; Jafri, Madiha J.; Astur, Robert S.; Pearlson, Godfrey D.

2009-01-01

Background: Driving while under the influence of alcohol is a major public health problem whose neural basis is not well understood. In a recently published fMRI study (Meda et al, 2009), our group identified five, independent critical driving-associated brain circuits whose inter-regional connectivity was disrupted by alcohol intoxication. However, the functional connectivity between these circuits has not yet been explored in order to determine how these networks communicate with each other during sober and alcohol-intoxicated states. Methods: In the current study, we explored such differences in connections between the above brain circuits and driving behavior, under the influence of alcohol versus placebo. Forty social drinkers who drove regularly underwent fMRI scans during virtual reality driving simulations following two alcohol doses, placebo and an individualized dose producing blood alcohol concentrations (BACs) of 0.10%. Results: At the active dose, we found specific disruptions of functional network connectivity between the frontal-temporal-basal ganglia and the cerebellar circuits. The temporal connectivity between these two circuits was found to be less correlated (p <0.05) when driving under the influence of alcohol. This disconnection was also associated with an abnormal driving behavior (unstable motor vehicle steering). Conclusions: Connections between frontal-temporal-basal ganglia and cerebellum have recently been explored; these may be responsible in part for maintaining normal motor behavior by integrating their overlapping motor control functions. These connections appear to be disrupted by alcohol intoxication, in turn associated with an explicit type of impaired driving behavior. PMID:20028354

Nrf2 Knockdown Disrupts the Protective Effect of Curcumin on Alcohol-Induced Hepatocyte Necroptosis.

PubMed

Lu, Chunfeng; Xu, Wenxuan; Zhang, Feng; Shao, Jiangjuan; Zheng, Shizhong

2016-12-05

It has emerged that hepatocyte necroptosis plays a critical role in chronic alcoholic liver disease (ALD). Our previous study has identified that the beneficial therapeutic effect of curcumin on alcohol-caused liver injury might be attributed to activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), whereas the role of curcumin in regulating necroptosis and the underlying mechanism remain to be determined. We first found that chronic alcohol consumption triggered obvious hepatocyte necroptosis, leading to increased expression of receptor-interacting protein 1, receptor-interacting protein 3, high-mobility group box 1, and phosphorylated mixed lineage kinase domain-like in murine livers. Curcumin dose-dependently ameliorated hepatocyte necroptosis and alleviated alcohol-caused decrease in hepatic Nrf2 expression in alcoholic mice. Then Nrf2 shRNA lentivirus was introduced to generate Nrf2-knockdown mice. Our results indicated that Nrf2 knockdown aggravated the effects of alcohol on liver injury and necroptosis and even abrogated the inhibitory effect of curcumin on necroptosis. Further, activated Nrf2 by curcumin inhibited p53 expression in both livers and cultured hepatocytes under alcohol stimulation. The next in vitro experiments, similar to in vivo ones, revealed that although Nrf2 knockdown abolished the suppression of curcumin on necroptosis of hepatocytes exposed to ethanol, p53 siRNA could clearly rescued the relative effect of curcumin. In summary, for the first time, we concluded that curcumin attenuated alcohol-induced hepatocyte necroptosis in a Nrf2/p53-dependent mechanism. These findings make curcumin an excellent candidate for ALD treatment and advance the understanding of ALD mechanisms associated with hepatocyte necroptosis.

Effect of hydro-alcoholic extract of Vernonia cinerea Less. against ethylene glycol-induced urolithiasis in rats

PubMed Central

Hiremath, Ravindra D.; Jalalpure, Sunil S.

2016-01-01

Objective: Aim of this study is to evaluate antiurolithiatic potential of whole plant hydro-alcoholic (30:70) extract of Vernonia cinerea Less. in accordance to its claims made in ancient literature and also being one of the ingredients of cystone, a marketed formulation widely used in the management of urolithiasis. Materials and Methods: To induce urolithiasis, 0.75% v/v ethylene glycol was administered orally for 14 days. The curative dose of 400 mg/kg b.w. and preventive doses of 100, 200, and 400 mg/kg b.w. were administered from 15th to 28th and 1st to 28 days, respectively. Cystone 750 mg/kg b.w. was selected as the reference standard for both curative and preventive doses. On 28th day, urinate of 24 h was collected and subjected for estimation of calcium, oxalate, and phosphates. Serum biochemical and kidney homogenate analysis was done for determination of renal oxalate contents. Results: The diseased Group II showed marked increase (P < 0.001 vs. normal Group I) in levels of urine calcium, oxalate, and phosphate. Serum creatinine, urea, and uric acid levels were also increased. Histopathological studies of kidney sections revealed significant changes. Treatment with hydro-alcoholic extract of V. cinerea showed significant (P < 0.01 vs. calculi-induced Group II) dose-dependent activity. A progressive increase in urine output, body weight, and decline in concentrations of stone-forming components such as calcium, oxalates, and phosphates was observed. Conclusion: It can be inferred that V. cinerea Less. is effective in ethylene glycol-induced urolithiasis and may have a potential in preventing and curing urolithiasis. PMID:27756957

Alcohol enhances oxysterol-induced apoptosis in human endothelial cells by a calcium-dependent mechanism.

PubMed

Spyridopoulos, I; Wischhusen, J; Rabenstein, B; Mayer, P; Axel, D I; Fröhlich, K U; Karsch, K R

2001-03-01

Controversy exists about the net effect of alcohol on atherogenesis. A protective effect is assumed, especially from the tannins and phenolic compounds in red wine, owing to their inhibition of low density lipoprotein (LDL) oxidation. However, increased atherogenesis occurs in subjects with moderate to heavy drinking habits. The purpose of this study was to investigate the influence of alcohol in combination with oxysterols on the endothelium. Cultured human arterial endothelial cells (HAECs) served as an in vitro model to test the cellular effects of various oxysterols. Oxysterols (7beta-hydroxycholesterol, 7-ketocholesterol, and cholesterol-5,6-epoxides), which are assumed to be the most toxic constituents of oxidized LDL, induced apoptosis in HAECs through calcium mobilization followed by activation of caspase-3. Ethanol, methanol, isopropanol, tert-butanol, and red wine all potentiated oxysterol-induced cell death up to 5-fold, paralleled by further induction of caspase-3. The alcohol effect occurred in a dose-dependent manner and reached a plateau at 0.05% concentration. Alcohol itself did not affect endothelial cell viability, nor did other solvents such as dimethyl sulfoxide mimic the alcohol effect. So far as the physiologically occurring oxysterols are concerned, this effect was apparent only for oxysterols oxidized at the steran ring. The possibility of alcohol facilitating the uptake of oxysterols into the cell was not supported by the data from an uptake study with radiolabeled compounds. Finally, alcohol in combination with oxysterols did cause a dramatic increase in cytosolic calcium influx. Blockage of calcium influx by the calcium channel blocker aurintricarboxylic acid or the calcium chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid abrogated the alcohol-mediated enhancement of oxysterol toxicity. We describe for the first time a mechanistic concept explaining possible adverse effects of alcohol in conjunction with physiologically occurring oxysterols on atherogenesis.

Effect of gamma irradiation on the color, structure and morphology of nickel-doped polyvinyl alcohol films: Alternative use as dosimeter or irradiation indicator

NASA Astrophysics Data System (ADS)

Raouafi, A.; Daoudi, M.; Jouini, K.; Charradi, K.; Hamzaoui, A. H.; Blaise, P.; Farah, K.; Hosni, F.

2018-06-01

Nickel-doped poly vinyl alcohol (PVA) films were developed for potential application in industrial sectors like radiation processing. We report in this paper the results of an experimental investigation of 60Co source γ-radiation effect on colorimetric, structural and morphological properties of PVA films doped with 0.5% Ni2+ ions (PVA/Ni2+). The PVA/Ni2+ films were irradiated by different gamma-radiation doses varying from 5 to 100 kGy. Color modification of films were studied using L∗, a∗ and b∗ color space measurements as function of the γ-dose and post-irradiation time. The visual change in all samples was verified by microstructure analysis, Fourier transforms infrared (FTIR) spectroscopy, X-Rays diffraction (XRD) and scanning electron microscopy (SEM). The color space exhibited a linear dose response at a dose ranging from 5 to 50 kGy, and then it reached saturation for higher γ-doses. The calculated color changes (ΔE) show a linear dose response relationship from 9.90 to 115.02 in the dose range from 0 to 50 kGy. It showed also the activation of stable color centers. The variability of the color change did not exceed 3% during 80 h (h) post-irradiation. Furthermore, the microstructure analysis evidenced that the color modification due to the optical activation of nickel-oxide (NiO) color center were obtained by complexing Ni2+ ions in irradiated PVA films. The obtained results inspire the possibility to use PVA films for the control process in industrial radiation facilities in dose range 5-50 kGy.

Acute disinhibiting effects of alcohol as a factor in risky driving behavior

PubMed Central

Fillmore, Mark T.; Blackburn, Jaime S.; Harrison, Emily L. R.

2008-01-01

Automobile crash reports show that up to 40% of fatal crashes in the United States involve alcohol and that younger drivers are over-represented. Alcohol use among young drivers is associated with impulsive and risky driving behaviors, such as speeding, which could contribute to their over-representation in alcohol-related crash statistics. Recent laboratory studies show that alcohol increases impulsive behaviors by impairing the drinker’s ability to inhibit inappropriate actions and that this effect can be exacerbated in conflict situations where the expression and inhibition of behavior are equally motivating. The present study tested the hypothesis that this response conflict might also intensify the disruptive effects of alcohol on driving performance. Fourteen subjects performed a simulated driving and a cued go/no-go task that measured their inhibitory control. Conflict was motivated in these tasks by providing equal monetary incentives for slow, careful behavior (e.g., slow driving, inhibiting impulses) and for quick, abrupt behavior (fast driving, disinhibition). Subjects were tested under two alcohol doses (0.65 g/kg and a placebo) that were administered twice: when conflict was present and when conflict was absent. Alcohol interacted with conflict to impair inhibitory control and to increase risky and impaired driving behavior on the drive task. Also, individuals whose inhibitory control was most impaired by alcohol displayed the poorest driving performance under the drug. The study demonstrates potentially serious disruptions to driving performance as a function of alcohol intoxication and response conflict, and points to inhibitory control as an important underlying mechanism. PMID:18325693

Final report of the addendum to the safety assessment of n-butyl alcohol as used in cosmetics.

PubMed

McLain, Valerie C

2008-01-01

n-Butyl Alcohol is a primary aliphatic alcohol historically used as a solvent in nail care cosmetic products, but new concentration of use data indicate that it also is being used at low concentrations in eye makeup, personal hygiene, and shaving cosmetic products. n-Butyl Alcohol has been generally recognized as safe for use as a flavoring substance in food and appears on the 1982 Food and Drug Administration (FDA) list of inactive ingredients for approved prescription drug products. n-Butyl Alcohol can be absorbed through the skin, lungs, and gastrointestinal tract. n-Butyl Alcohol may be formed by hydrolysis of butyl acetate in the blood, but is rapidly oxidized. The single oral dose LD(50) of n-Butyl Alcohol for rats was 0.79 to 4.36 g/kg. The dermal LD(50) for rabbits was 4.2 g/kg. Inhalation toxicity studies in humans demonstrate sensory irritation of the upper respiratory tract, but only at levels above 3000 mg/m(3). Animal studies demonstrate intoxication, restlessness, ataxia, prostration, and narcosis. Exposures of rats to levels up to 4000 ppm failed to produce hearing defects. High concentrations of n-Butyl Alcohol vapors can be fatal. Ocular irritation was observed for n-Butyl alcohol at 0.005 ml of a 40% solution. The behavioral no-effect dose for n-Butyl Alcohol injected subcutaneously (s.c.) was 120 mg/kg. Fetotoxicity has been demonstrated, but only at maternally toxic levels (1000 mg/kg). No significant behavioral or neurochemical effects were seen in offspring following either maternal or paternal exposure to 3000 or 6000 ppm. n-Butyl Alcohol was not mutagenic in Ames tests, did not induce sister-chromatid exchange or chromosome breakage in chick embryos or Chinese hamster ovary cells, did not induce micronuclei formation in V79 Chinese hamster cells, did not have any chromosome-damaging effects in a mouse micronucleus test, and did not impair chromosome distribution in the course of mitosis. Clinical testing of n-Butyl Alcohol for nonimmunological contact urticaria was negative in 105 subjects. Repeat-insult patch test (RIPT) studies of nail colors and enamels containing 3% n-Butyl Alcohol in one study produced reactions on challenge, but further study linked significant positive reactions to another solvent. In other RIPT studies, only minimal reactions were reported. A photopatch test demonstrated that a nail enamel containing 3% n-Butyl Alcohol resulted in no reactions. Workers complained of ocular irritation, disagreeable odor, slight headache and vertigo, slight irritation of nose and throat, and dermatitis of the fingers and hands when the air concentration of n-Butyl Alcohol was greater than 50 ppm, as compared to an odor threshold in air of 0.83 ppm. The available safety test data were considered adequate to support the safety of n-Butyl Alcohol in all cosmetic product categories in which it is currently used.

Alcohol Alters the Activation of ERK1/2, a Functional Regulator of Binge Alcohol Drinking in Adult C57BL/6J Mice

PubMed Central

Agoglia, Abigail E.; Sharko, Amanda C.; Psilos, Kelly E.; Holstein, Sarah E.; Reid, Grant T.; Hodge, Clyde W.

2014-01-01

Background Binge alcohol drinking is a particularly risky pattern of alcohol consumption that often precedes alcohol dependence and addiction. The transition from binge alcohol drinking to alcohol addiction likely involves mechanisms of synaptic plasticity and learning in the brain. The mitogen-activated protein kinase (MAPK) signaling cascades have been shown to be involved in learning and memory, as well as the response to drugs of abuse, but their role in binge alcohol drinking remains unclear. The present experiments were designed to determine the effects of acute alcohol on extracellular signaling related kinases (ERK1/2) expression and activity, and to determine whether ERK1/2 activity functionally regulates binge-like alcohol drinking. Methods Adult male C57BL/6J mice were injected with ethanol (3.0 mg/kg, IP) 10, 30 or 90 minutes prior to brain tissue collection. Next, mice that were brought to freely consume unsweetened ethanol in a binge-like access procedure were pretreated with the MEK1/2 inhibitor SL327 or the p38 MAP kinase inhibitor SB239063. Results Acute ethanol increased pERK1/2 immunoreactivity relative to vehicle in brain regions known to be involved in drug reward and addiction, including the central amygdala and prefrontal cortex. However, ethanol decreased pERK1/2 immunoreactivity relative to vehicle in the nucleus accumbens core. SB239063 pretreatment significantly decreased ethanol consumption only at doses that also produced nonspecific locomotor effects. SL327 pretreatment significantly increased ethanol, but not sucrose, consumption without inducing generalized locomotor effects. Conclusions These findings indicate that ERK1/2MAPK signaling regulates binge-like alcohol drinking. Since alcohol increased pERK1/2 immunoreactivity relative to vehicle in brain regions known to regulate drug self-administration, SL327 may have blocked this direct pharmacological effect of alcohol and thereby inhibited the termination of binge-like drinking. PMID:25703719

Dose–response study of chronic alcohol induced changes in sleep patterns in rats

PubMed Central

Mukherjee, Sanjib; Kazerooni, Morvarid; Simasko, Steven M.

2008-01-01

The goal of the present study was to determine an optimum exposure regimen for alterations in sleep induced by chronic alcohol treatments in rats. We used two different exposure routes (alcohol in water and alcohol in liquid diet at two different doses in each regimen (6% and 12% alcohol in water and 3% and 6% alcohol in liquid diet)). All treatments were for 6 weeks. We found the effects of the 6% and 12% in water and 3% in liquid diet to be very similar; all three produced increases in slow-wave sleep (SWS) only in the dark period with no changes in rapid-eye-movement sleep (REMS). On the other hand 6% alcohol in liquid diet caused much more dramatic changes, with alterations in both SWS and REMS in both the dark and light periods. These animals spent less time in SWS and REMS during the light period but more time in SWS and REMS in the dark period. Additionally, the variation of slow-wave amplitude (SWA) across day and night in this group of alcoholic animals is blunted with the loss of the peak of SWA at the beginning of light onset compared to the other groups. We conclude that future alcohol treatment regimens used to investigate the effects of alcohol on sleep in adult rats should use an exposure protocol of at least 6 weeks with 6% alcohol in liquid diet. PMID:18387599

Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

PubMed Central

Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

2015-01-01

The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

The biological responses to resveratrol and other polyphenols from alcoholic beverages

PubMed Central

Brown, Lindsay; Kroon, Paul A.; Das, Dipak K.; Das, Samarjit; Tosaki, Arpad; Chan, Vincent; Singer, Manfred V.; Feick, Peter

2009-01-01

Although excessive consumption of ethanol in alcoholic beverages causes multi-organ damage, moderate consumption, particularly of red wine, is protective against all-cause mortality. These protective effects could be due to one or many components of the complex mixture of bioactive compounds present in red wine including flavonols, monomeric and polymeric flavan-3-ols, highly coloured anthocyanins as well as phenolic acids and the stilbene polyphenol, resveratrol. The therapeutic potential of resveratrol, firstly in cancer chemoprevention and then later for cardioprotection, has stimulated many studies on the possible mechanisms of action. Further indications for resveratrol have been developed, including the prevention of age-related disorders such as neurodegenerative diseases, inflammation, diabetes and cardiovascular disease. These improvements are remarkably similar yet there is an important dichotomy: low doses improve cell survival as in cardio- and neuro-protection yet high doses increase cell death as in cancer treatment. Fewer studies have examined the responses to other components of red wine, but the results have, in general, been similar to resveratrol. If the non-alcoholic constitutents of red wine are to become therapeutic agents, their ability to get to the sites of action needs to be understood. This mini-review summarizes recent studies on the possible mechanisms of action, potential therapeutic uses and bioavailability of the non-alcoholic constitutents of alcoholic beverages, in particular resveratrol and other polyphenols. PMID:19519720

Short- and medium-term effects of light to moderate alcohol intake on glycaemic control in diabetes mellitus: a systematic review and meta-analysis of randomized trials.

PubMed

Hirst, J A; Aronson, J K; Feakins, B G; Ma, C; Farmer, A J; Stevens, R J

2017-05-01

People with diabetes are told that drinking alcohol may increase their risk of hypoglycaemia. To report the effects of alcohol consumption on glycaemic control in people with diabetes mellitus. Medline, EMBASE and the Cochrane Library databases were searched in 2015 to identify randomized trials that compared alcohol consumption with no alcohol use, reporting glycaemic control in people with diabetes. Data on blood glucose, HbA 1c and numbers of hypoglycaemic episodes were pooled using random effects meta-analysis. Pooled data from nine short-term studies showed no difference in blood glucose concentrations between those who drank alcohol in doses of 16-80 g (median 20 g, 2.5 units) compared with those who did not drink alcohol at 0.5, 2, 4 and 24 h after alcohol consumption. Pooled data from five medium-term studies showed that there was no difference in blood glucose or HbA 1c concentrations at the end of the study between those who drank 11-18 g alcohol/day (median 13 g/day, 1.5 units/day) for 4-104 weeks and those who did not. We found no evidence of a difference in number of hypoglycaemic episodes or in withdrawal rates between randomized groups. Studies to date have not provided evidence that drinking light to moderate amounts of alcohol, with or without a meal, affects any measure of glycaemic control in people with Type 2 diabetes. These results suggest that current advice that people with diabetes do not need to refrain from drinking moderate quantities of alcohol does not need to be changed; risks to those with Type 1 diabetes remain uncertain. © 2016 Diabetes UK.

Transcriptome changes induced in vitro by alcohol-containing mouthwashes in normal and dysplastic oral keratinocytes.

PubMed

Fox, Simon A; Currie, Sean S; Dalley, Andrew J; Farah, Camile S

2018-05-01

The role of alcohol-containing mouthwash as a risk factor for the development of oral cancer is a subject of conflicting epidemiological evidence in the literature despite alcohol being a recognised carcinogen. The aim of this study was to use in vitro models to investigate mechanistic and global gene expression effects of exposure to alcohol-containing mouthwash. Two brands of alcohol-containing mouthwash and their alcohol-free counterparts were used to treat two oral cell lines derived from normal (OKF6-TERT) and dysplastic (DOK) tissues. Genotoxicity was determined by Comet assay. RNA-seq was performed using the Ion Torrent platform. Bioinformatics analysis used R/Bioconductor packages with differential expression using DEseq2. Pathway enrichment analysis used EnrichR with the WikiPathways and Kegg databases. Both cell lines displayed dose-dependent DNA damage in response to acute exposure to ethanol and alcohol-containing mouthwashes as well as alcohol-free mouthwashes reconstituted with ethanol as shown by Comet assay. The transcriptomic effects of alcohol-containing mouthwash exposure were more complex with significant differential gene expression ranging from >2000 genes in dysplastic (DOK) cells to <100 genes in normal (OKF6-TERT) cells. Pathway enrichment analysis in DOK cells revealed alcohol-containing mouthwashes showed common features between the two brands used including DNA damage response as well as cancer-associated pathways. In OKF6-TERT cells, the most significantly enriched pathways involved inflammatory signalling. Alcohol-containing mouthwashes are genotoxic in vitro to normal and dysplastic oral keratinocytes and induce widespread changes in gene expression. Dysplastic cells are more susceptible to the transcriptomic effects of mouthwash. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gender differences in treatment and clinical characteristics among patients receiving extended release naltrexone.

PubMed

Herbeck, Diane M; Jeter, Kira E; Cousins, Sarah J; Abdelmaksoud, Reham; Crèvecoeur-MacPhail, Desirée

2016-01-01

Further research is needed to investigate real-world acceptability of extended-release naltrexone for alcohol and opioid use disorders, and potential gender differences. This study examines treatment and clinical characteristics among men and women receiving extended-release naltrexone in a large, publicly funded substance use disorder treatment system (N = 465; 52% female). Patient demographics, treatment characteristics, and the number of extended-release naltrexone doses received were collected from administrative data and treatment program staff. Additionally, patients provided information on experiences with extended-release naltrexone in an open-ended format at 1, 2, and 3 weeks following their first injection. For a subsample of patients (N = 220), alcohol/opioid cravings and specific adverse effects were also assessed. Compared to men, women reported experiencing a higher rate and mean number of adverse effects. Overall, craving scores showed substantial reductions over time. However, among patients taking extended-release naltrexone for alcohol use, women showed a significantly greater reduction in craving scores compared to men. No gender differences were observed in the number of extended-release naltrexone doses received. Although women may have a greater need for additional support in managing early adverse effects, extended-release naltrexone as an adjunct to psychosocial treatment may be an acceptable and promising treatment approach for both men and women, and particularly for women prescribed extended-release naltrexone for alcohol use. This study contributes further information on patients' experiences during the early course of extended-release naltrexone treatment in real-world settings. Understanding these experiences may assist policy makers and treatment providers in addressing challenges of implementing this treatment into wider practice.

Effect of non-nutritive sugars to decrease the survivorship of spotted wing drosophila, Drosophila suzukii

USDA-ARS?s Scientific Manuscript database

In this study, we investigated the effects of non-nutritive sugars and sugar alcohols on the survivorship of spotted wing drosophila, Drosophila suzukii, and found erythritol and erythrose as potentially toxic to the fly. In a dose-dependent study, erythritol and erythrose significantly reduced fly ...

Differences in Acute Alcohol-Induced Behavioral Responses Among Zebrafish Populations

PubMed Central

Gerlai, Robert; Ahmad, Fahad; Prajapati, Sonal

2009-01-01

Background With the arsenal of genetic tools available for zebrafish, this species has been successfully used to investigate the genetic aspects of human diseases from developmental disorders to cancer. Interest in the behavior and brain function of zebrafish is also increasing as CNS disorders may be modeled and studied with this species. Alcoholism and alcohol abuse are among the most devastating and costliest diseases. However, the mechanisms of these diseases are not fully understood. Zebrafish has been proposed as a model organism to study such mechanisms. Characterization of alcohol’s effects on zebrafish is a necessary step in this research. Methods Here, we compare the effects of acute alcohol (EtOH) administration on the behavior of zebrafish from 4 distinct laboratory-bred populations using automated as well as observation based behavioral quantification methods. Results Alcohol treatment resulted in significant dose-dependent behavioral changes but the dose–response trajectories differed among zebrafish populations. Conclusions The results demonstrate for the first time a genetic component in alcohol responses in adult zebrafish and also show the feasibility of high throughput behavioral screening. We discuss the exploration and exploitation of the genetic differences found. PMID:18652595

Selective impairment of hippocampal neurogenesis by chronic alcoholism: Protective effects of an antioxidant

PubMed Central

Herrera, Daniel G.; Yagüe, Almudena G.; Johnsen-Soriano, Siv; Bosch-Morell, Francisco; Collado-Morente, Lucía; Muriach, Maria; Romero, Francisco J.; García-Verdugo, J. Manuel

2003-01-01

A major pathogenic mechanism of chronic alcoholism involves oxidative burden to liver and other cell types. We show that adult neurogenesis within the dentate gyrus of the hippocampus is selectively impaired in a rat model of alcoholism, and that it can be completely prevented by the antioxidant ebselen. Rats fed for 6 weeks with a liquid diet containing moderate doses of ethanol had a 66.3% decrease in the number of new neurons and a 227–279% increase in cell death in the dentate gyrus as compared with paired controls. Neurogenesis within the olfactory bulb was not affected by alcohol. Our studies indicate that alcohol abuse, even for a short duration, results in the death of newly formed neurons within the adult brain and that the underlying mechanism is related to oxidative or nitrosative stress. Moreover, these findings suggest that the impaired neurogenesis may be a mechanism mediating cognitive deficits observed in alcoholism. PMID:12792022

Impairment of manual but not saccadic response inhibition following acute alcohol intoxication.

PubMed

Campbell, Anne Eileen; Chambers, Christopher D; Allen, Christopher P G; Hedge, Craig; Sumner, Petroc

2017-12-01

Alcohol impairs response inhibition; however, it remains contested whether such impairments affect a general inhibition system, or whether affected inhibition systems are embedded in, and specific to, each response modality. Further, alcohol-induced impairments have not been disambiguated between proactive and reactive inhibition mechanisms, and nor have the contributions of action-updating impairments to behavioural 'inhibition' deficits been investigated. Forty Participants (25 female) completed both a manual and a saccadic stop-signal reaction time (SSRT) task before and after a 0.8g/kg dose of alcohol and, on a separate day, before and after a placebo. Blocks in which participants were required to ignore the signal to stop or make an additional 'dual' response were included to obtain measures of proactive inhibition as well as updating of attention and action. Alcohol increased manual but not saccadic SSRT. Proactive inhibition was weakly reduced by alcohol, but increases in the reaction times used to baseline this contrast prevent clear conclusions regarding response caution. Finally, alcohol also increased secondary dual response times of the dual task uniformly as a function of the delay between tasks, indicating an effect of alcohol on action-updating or execution. The modality-specific effects of alcohol favour the theory that response inhibition systems are embedded within response modalities, rather than there existing a general inhibition system. Concerning alcohol, saccadic control appears relatively more immune to disruption than manual control, even though alcohol affects saccadic latency and velocity. Within the manual domain, alcohol affects multiple types of action updating, not just inhibition. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of gamma ray on poly(lactic acid)/poly(vinyl acetate-co-vinyl alcohol) blends as biodegradable food packaging films

NASA Astrophysics Data System (ADS)

Razavi, Seyed Mohammad; Dadbin, Susan; Frounchi, Masoud

2014-03-01

Poly(lactic acid) (PLA)/poly(vinyl acetate-co-vinyl alcohol) [P(VAc-co-VA)] blends as new transparent film packaging materials were prepared at various blend compositions and different vinyl alcohol contents. The blends and pure PLA were irradiated by gamma rays to investigate the extent of changes in the packaging material during gamma ray sterilization process. The miscibility of the blends was dependent on the blend composition and vinyl alcohol content; gamma irradiation had little effect on the extent of miscibility. The glass transition temperature of pure PLA and PLA/P(VAc-co-VA) miscible blends reduced after irradiation. On the other hand in PLA/P(VAc-co-VA) immiscible blends, while the glass transition temperature of the PLA phase decreased; that of the copolymer phase slightly increased. The reduction in the glass transition was about 10 percent for samples irradiated with 50 kGy indicating dominance of chain scission of PLA molecules at high irradiation dose. The latter was verified by drop in mechanical properties of pure PLA after exposing to gamma irradiation at 50 kGy. Blending of PLA with the copolymer P(VAc-co-VA) compensated greatly the adverse effects of irradiation on PLA. The oxygen-barrier property of the blend was superior to the neat PLA and remained almost intact with irradiation. The un-irradiated and irradiated blends had excellent transparency. Gamma ray doses used for sterilization purposes are usually less than 20 kGy. It was shown that gamma irradiation at 20 kGy had no or little adverse effects on PLA/P(VAc-co-VA) blends mechanical and gas barrier properties.

Early post-natal neuroactive steroid manipulation modulates ondansetron effects on initial periods of alcohol consumption in rats.

PubMed

Bartolomé, Iris; Llidó, Anna; Darbra, Sònia; Pallarès, Marc

2018-06-21

Neuroactive steroids (NS) such as allopregnanolone are crucial for brain development and adult behaviour. Early post-natal alterations of NS by administering finasteride induce a decrease in the sensitivity to stimulant effects of low alcohol doses, an increase in alcohol consumption, and a decrease in ventrostriatal dopamine and serotonin levels. The aim of the present study is to observe if the effects of the 5HT3 receptor antagonist ondansetron on initial alcohol consumption are modulated by post-natal NS manipulation. For this purpose, allopregnanolone, finasteride, or vehicle was injected from day 5 to 9. In adulthood, a novel object preference test was carried out in order to detect a possible novelty-seeking pattern in our animals, which has been related to vulnerability to drug abuse. The subjects then had access to two bottles (alcohol or control solutions) one hour daily for two consecutive weeks. Ondansetron (0.01 mg/kg, 0.1 mg/kg or vehicle) was administered before the hour of consumption in the initial phase (days 1, 2, 3) of the procedure, and after prolonged alcohol intake (days 11, 12, 13). Results indicated that finasteride animals showed a higher preference to explore the new object, as well as a higher alcohol consumption than the rest of the groups. Moreover, 0.1 mg/kg of ondansetron decreased alcohol consumption, but only in the post-natal finasteride group, suggesting a possible increase in 5HT3 receptor sensitivity in these animals. In conclusion, NS manipulation in crucial stages of development, such as early post-natal periods, seems to play an important role on the effects of ondansetron on alcohol intake and in the vulnerability to develop drug use or abuse. Copyright © 2018. Published by Elsevier Inc.

Breath alcohol analysis incorporating standardization to water vapour is as precise as blood alcohol analysis.

PubMed

Grubb, D; Rasmussen, B; Linnet, K; Olsson, S G; Lindberg, L

2012-03-10

A novel breath-alcohol analyzer based on the standardization of the breath alcohol concentration (BrAC) to the alveolar-air water vapour concentration has been developed and evaluated. The present study compares results with this particular breath analyzer with arterial blood alcohol concentrations (ABAC), the most relevant quantitative measure of brain alcohol exposure. The precision of analysis of alcohol in arterial blood and breath were determined as well as the agreement between ABAC and BrAC over time post-dosing. Twelve healthy volunteers were administered 0.6g alcohol/kg bodyweight via an orogastric tube. Duplicate breath and arterial blood samples were obtained simultaneously during the absorption, distribution and elimination phases of the alcohol metabolism with particular emphasis on the absorption phase. The precision of the breath analyzer was similar to the determination of blood alcohol concentration by headspace gas chromatography (CV 2.40 vs. 2.38%, p=0.43). The ABAC/BrAC ratio stabilized 30min post-dosing (2089±99; mean±SD). Before this the BrAC tended to underestimate the coexisting ABAC. In conclusion, breath alcohol analysis utilizing standardization of alcohol to water vapour was as precise as blood alcohol analysis, the present "gold standard" method. The BrAC reliably predicted the coexisting ABAC from 30min onwards after the intake of alcohol. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Low-dose prazosin alone and in combination with propranolol or naltrexone: effects on ethanol and sucrose seeking and self-administration in the P rat.

PubMed

Verplaetse, Terril L; Czachowski, Cristine L

2015-08-01

Evidence suggests that the noradrenergic system mediates ethanol reinforcement. However, preclinical studies suggest that noradrenergic antagonists block other oral reinforcers indicating possible unwanted secondary medication effects. This study examined combinations of low-dose prazosin with propranolol or naltrexone using a behavioral paradigm that separately assesses reinforcer seeking and self-administration. Male alcohol-preferring (P) rats (n = 20/experiment) were trained to complete a response requirement (RR) resulting in access to 1 % sucrose (n = 10) or 10 % ethanol (n = 10) for 20 min. Rats received vehicle, prazosin alone (0.125, 0.25, 0.5, and 1.0 mg/kg, intraperitoneally (IP)), or prazosin in combination with propranolol (5 mg/kg (IP); Exp. 1) or in combination with naltrexone (0.03 mg/kg, subcutaneously (SC); Exp. 2). For Exp. 1, prazosin alone effectively decreased sucrose seeking more than ethanol seeking, but decreased ethanol self-administration only. Propranolol alone effectively decreased ethanol seeking more than sucrose seeking and decreased ethanol intake only. At some dose combinations, there was a greater attenuation of ethanol and sucrose intake relative to either drug alone. For Exp. 2, prazosin alone and naltrexone alone were effective in decreasing ethanol seeking and intake only. Combination treatment was more effective than either drug alone at decreasing ethanol seeking and consumption and sucrose intake, but not sucrose seeking. Propranolol and naltrexone alone were specific to ethanol indicating that low doses of either medication may be beneficial in treating alcohol use disorders. Prazosin in combination with propranolol or naltrexone was more effective than either drug alone and also reduced sucrose-reinforced behaviors. These data suggest that the noradrenergic system is a viable target for developing treatment approaches for problem drinkers.

Low-Dose Prazosin Alone and in Combination with Propranolol or Naltrexone: Effects on Ethanol- and Sucrose-Seeking and Self-Administration in the P Rat

PubMed Central

Verplaetse, Terril L.; Czachowski, Cristine L.

2015-01-01

Rationale Evidence suggests that the noradrenergic system mediates ethanol-reinforcement. However, preclinical studies suggest that noradrenergic antagonists block other oral reinforcers indicating possible unwanted secondary medication effects. Methods This study examined combinations of low-dose prazosin with propranolol or naltrexone using a behavioral paradigm that separately assesses reinforcer-seeking and self-administration. Male alcohol-preferring (P) rats (n=20/experiment) were trained to complete a response requirement (RR) resulting in access to 1% sucrose (n=10) or 10% ethanol (n=10) for 20min. Rats received vehicle, prazosin alone (0.125, 0.25, 0.5, 1.0 mg/kg; intraperitoneally (IP)) or prazosin in combination with propranolol (5 mg/kg (IP); Exp1) or in combination with naltrexone (0.03 mg/kg (subcutaneously (SC); Exp2). Results For Exp1, prazosin alone effectively decreased sucrose-seeking more than ethanol-seeking, but decreased ethanol self-administration only. Propranolol alone effectively decreased ethanol-seeking more than sucrose-seeking and decreased ethanol intake only. At some dose combinations, there was a greater attenuation of ethanol and sucrose intake relative to either drug alone. For Exp2, prazosin alone and naltrexone alone were effective in decreasing ethanol-seeking and intake only. Combination treatment was more effective than either drug alone at decreasing ethanol-seeking and consumption and sucrose intake, but not sucrose-seeking. Conclusions Propranolol and naltrexone alone were specific to ethanol indicating that low doses of either medication may be beneficial in treating alcohol use disorders. Prazosin in combination with propranolol or naltrexone was more effective than either drug alone, but also reduced sucrose-reinforced behaviors. These data suggest that the noradrenergic system is a viable target for developing treatment approaches for problem drinkers. PMID:25743758

The effects of paracetamol (acetaminophen) on hepatic tests in patients who chronically abuse alcohol - a randomized study.

PubMed

Dart, R C; Green, J L; Kuffner, E K; Heard, K; Sproule, B; Brands, B

2010-08-01

Retrospective accounts suggest that therapeutic doses of paracetamol can produce severe hepatic injury in patients with putative high-risk conditions, including alcoholism and infectious hepatitis. Metabolism of paracetamol to its hepatotoxic metabolite is enhanced in patients who abuse alcohol, who also have compromised liver defences from depressed hepatic glutathione. To determine the effect of paracetamol on serum liver tests of newly abstinent subjects who abuse alcohol, including subjects with hepatitis C infection. A randomized, double-blind, placebo-controlled study. Adult alcohol abusers with a current drinking episode longer than 7 days received either placebo or paracetamol 4 g/day for 5 days. Of 142 subjects enrolled, 74 received paracetamol and 68 received placebo. Mean ALT activity during treatment increased from 48 to 62 IU/L in the paracetamol group and from 47 to 49 IU/L in the placebo group. Maximum ALT was 238 and 249 IU/L in the paracetamol and control groups respectively. The INR remained unchanged and serum bilirubin decreased in both groups. Subgroup analyses for subjects with alcoholic hepatitis, hepatitis C virus antibody and other subgroups showed no statistical difference between groups. Administration of paracetamol 4 g/day appears safe in newly abstinent patients who abuse alcohol.

Does the Neuroimmune Modulator Ibudilast Alter Food Craving? Results in a Sample With Alcohol Use Disorder.

PubMed

Cummings, Jenna R; Tomiyama, A Janet; Ray, Lara A

2018-05-21

Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor. A randomized, placebo-control, crossover human laboratory trial advanced IBUD development for alcohol use disorder and found that IBUD reduced tonic levels of alcohol craving. Given the importance of considering medication effects on other appetitive behavior, the present study tested the effect of IBUD (50 mg bid) on food craving. The present study was a secondary data analysis of the trial of IBUD in non-treatment seekers with alcohol use disorder (N = 19). High-fat/high-sugar food craving was measured daily. Moreover, because substantial literatures show that small alcohol doses and psychological stress increase eating of high-fat/high-sugar food, craving for high-fat/high-sugar food was measured after alcohol infusion and stress reactivity. Results indicated that IBUD did not alter tonic high-fat/high-sugar food craving. Alcohol infusion did not generally increase high-fat/high-sugar food craving but psychological stress did. Likewise, IBUD did not affect high-fat/high-sugar food craving after alcohol infusion but IBUD did increase high-fat/high-sugar food craving after psychological stress. Follow-up analyses revealed that, among individuals with lower depressive symptomatology, IBUD compared to placebo heightened the effect of psychological stress on high-fat/high-sugar food craving. These results advance the development of IBUD for addiction indications by demonstrating that IBUD compared to placebo does not suppress other appetitive responses, namely craving for high-fat/high-sugar food among individuals with alcohol use disorder.

The Effect of Taraxacum officinale Hydroalcoholic Extract on Blood Cells in Mice

PubMed Central

Modaresi, Mehrdad; Resalatpour, Narges

2012-01-01

Objectives. Dandelion (Taraxacum officinale) is a herbaceous perennial plant of the family Asteraceae and has medicinal and culinary uses. Dandelion has been used as a remedy for anemia, purifing the blood, and providing immune modulation. Therefore, the aim of this study was to investigate the effect of hydro alcoholic extract on blood cells in mice. Methods. Five groups each including ten adult female (Balb/C) mice weighing 30 ± 5 g were chosen. Normal saline was administered as placebo for group, and dandelion hydro alcoholic extract in doses of 50,100, and 200 mg/kg was injected intraperitoneally for 20 days to test groups and the last group was control group.WBC, RBC, HB, HCT, platelet, and other cells were measured with automated cell counter. Main Results. The number of RBC and the rate of HB in three doses of 100 and 200 mg/kg significantly increased (P < 0.05). As compared with control group, the number of WBC in three doses of 50, 100, and 200 mg/kg increased, but it was significantly in 200 mg/kg dandelion treated group as compared with control group(P < 0.05). The rate of platelet in three doses of 50, 100 and 200 mg/kg significantly decreased as compared with control group (P < 0.01). 3 doses of dandelion increased lymphocyte numbers significantly compared with controls. Conclusion. The study indicates efficacy of dandelion extract on RBC and HB in doses of 50, 100, and 200 mg/kg and in 200 mg/kg on WBC to achieve normal body balance. PMID:22844289

In vitro dermal disposition of abamectin (avermectin B(1)) in livestock.

PubMed

Baynes, Ronald E

2004-06-01

Many avermectins are approved for topical application in domestic animals. However, extralabel use may result in significant dermal absorption and consequently the potential for adverse effects or violative residues. The primary aim of this study was to assess dermal disposition of abamectin in vitro in bovine, caprine, ovine, and porcine skin dosed in 100% isopropanol, commercial alcohol-based (Ivomec), or oil-based (Eprinex) formulations. Skin sections were perfused in a flow-through diffusion cell system for 8 h, and the disposition of radiolabel abamectin was determined from perfusate and skin samples. Abamectin absorption ranged from 0.09% to 0.20% dose and there were no significant differences between formulations in each species. Isopropanol significantly increased skin deposition in all species when compared to the oil formulation. Absorption was significantly greater in bovine skin than in porcine skin for the isopropanol-containing formulations, but there were no significant species differences for the oil formulation. While significant levels (11.69-50.23% dose) remained on the skin surface, the highest levels deposited in viable skin were observed in caprine skin (28.09% dose) and the lowest levels were in porcine skin (1.50% dose) which could lead to systemic absorption. In summary, these 8-h experiments demonstrated that the alcohol-based formulations compared to oil-based formulations enhanced abamectin absorption and skin deposition in several animal species, and this effect is more likely to be observed in ruminant species than in porcine species.

Hypersynchrony in MEG spectral amplitude in prospectively-identified 6-month-old infants prenatally exposed to alcohol.

PubMed

Stephen, Julia M; Flynn, Lucinda; Kabella, Danielle; Schendel, Megan; Cano, Sandra; Savage, Daniel D; Rayburn, William; Leeman, Lawrence M; Lowe, Jean; Bakhireva, Ludmila N

2018-01-01

Early identification of children who experience developmental delays due to prenatal alcohol exposure (PAE) remains a challenge for individuals who do not exhibit facial dysmorphia. It is well-established that children with PAE may still exhibit the cognitive and behavioral difficulties, and individuals without facial dysmorphia make up the majority of individuals affected by PAE. This study employed a prospective cohort design to capture alcohol consumption patterns during pregnancy and then followed the infants to 6 months of age. Infants were assessed using magnetoencephalography to capture neurophysiological indicators of brain development and the Bayley Scales of Infant Development-III to measure behavioral development. To account for socioeconomic and family environmental factors, we employed a two-by-two design with pregnant women who were or were not using opioid maintenance therapy (OMT) and did or did not consume alcohol during pregnancy. Based on prior studies, we hypothesized that infants with PAE would exhibit broad increased spectral amplitude relative to non-PAE infants. We also hypothesized that the developmental shift from low to high frequency spectral amplitude would be delayed in infants with PAE relative to controls. Our results demonstrated broadband increased spectral amplitude, interpreted as hypersynchrony, in PAE infants with no significant interaction with OMT. Unlike prior EEG studies in neonates, our results indicate that this hypersynchrony was highly lateralized to left hemisphere and primarily focused in temporal/lateral frontal regions. Furthermore, there was a significant positive correlation between estimated number of drinks consumed during pregnancy and spectral amplitude revealing a dose-response effect of increased hypersynchrony corresponding to greater alcohol consumption. Contrary to our second hypothesis, we did not see a significant group difference in the contribution of low frequency to high frequency amplitude at 6 months of age. These results provide new evidence that hypersynchrony, previously observed in neonates prenatally exposed to high levels of alcohol, persists until 6 months of age and this measure is detectable with low to moderate exposure of alcohol with a dose-response effect. These results indicate that hypersynchrony may provide a sensitive early marker of prenatal alcohol exposure in infants up to 6 months of age.

Influence of lifestyle on vitamin bioavailability.

PubMed

van den Berg, Henk; van der Gaag, Martijn; Hendriks, Henk

2002-01-01

In this review the effects of lifestyle factors, especially alcohol consumption, on vitamin bioavailability are summarized and discussed. Alcohol effects are clearly dose-dependent. Excessive chronic alcohol intake is generally associated with vitamin deficiency (especially folate, thiamine, and vitamin B6) due to malnutrition, malabsorption, and ethanol toxicity. Effects of moderate alcohol use are mainly explained by a lower vitamin intake. In the case of vitamin A and beta-carotene, effects on post-absorptive (lipoprotein) metabolism have been demonstrated. In one diet-controlled crossover study, alcohol consumption resulted in an increase in the plasma vitamin B6 (PLP) content, especially after beer consumption (containing vitamin B6), but also after wine and spirit consumption (not containing vitamin B6). Smoking is also associated with a lower dietary vitamin intake. In the case of vitamin C, B12, folate, and beta-carotene, evidence has been presented for effects on postabsorptive metabolism, due to smoke-induced oxidative stress and/or vitamin inactivation. For vitamin E a direct effect of smoking on absorption has been demonstrated. There is no convincing evidence that low-fat diets negatively affect fat-soluble vitamin absorption, but cholesterol-lowering compounds (diets), or unabsorbable fat substitutes, may do so. Vitamin bioavailability may be compromised from certain vegetables (particularly raw), and/or from high-fiber foods, because of limited digestion and inefficient release of vitamins from the food matrix.

WOMEN’S SOCIAL BEHAVIOR WHEN MEETING NEW MEN: THE INFLUENCE OF ALCOHOL AND CHILDHOOD SEXUAL ABUSE

PubMed Central

Parks, Kathleen A.; Hequembourg, Amy L.; Dearing, Ronda L.

2008-01-01

Heavy alcohol consumption (Testa & Parks, 1996) and childhood sexual abuse (CSA; Messman-Moore & Long, 2003) have been associated with adult sexual victimization. We examined the social behavior of 42 women under two alcohol conditions (high dose and low dose) in a bar laboratory. Women were videotaped interacting with a man they had just met. Women in the higher dose condition engaged in more open body position and talked, stood, and walked more than women in the lower dose condition. These behaviors are consistent with signs of intoxication or romantic interest. The women in the high-dose condition also frowned more than women in the low-dose condition. An increase in frowning could indicate less comfort or may be considered consistent with an increase in animation during the social interaction given the concomitant increase in other behaviors. Thus, the nonverbal behavior of women in the high-dose condition could be interpreted as mixed signals. CSA victims exhibited fewer head movements (e.g., nods), were less animated, and frowned more than non-CSA victims. These behaviors convey reticence or possibly even anxiety or discomfort during the social interaction. Thus, the nonverbal behavior of women with a history of CSA may convey an unease that could be viewed by a potential perpetrator as vulnerability. Our findings suggest that both acute alcohol consumption and history of CSA may influence nonverbal social behavior and may influence risk for sexual assault by sending mixed cues of romantic interest or signs of vulnerability to potential perpetrators. PMID:18668186

Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

PubMed

Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

2013-03-01

Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Ethanol Forensic Toxicology.

PubMed

Perry, Paul J; Doroudgar, Shadi; Van Dyke, Priscilla

2017-12-01

Ethanol abuse can lead to negative consequences that oftentimes result in criminal charges and civil lawsuits. When an individual is suspected of driving under the influence, law enforcement agents can determine the extent of intoxication by measuring the blood alcohol concentration (BAC) and performing a standardized field sobriety test. The BAC is dependent on rates of absorption, distribution, and elimination, which are influenced mostly by the dose of ethanol ingested and rate of consumption. Other factors contributing to BAC are gender, body mass and composition, food effects, type of alcohol, and chronic alcohol exposure. Because of individual variability in ethanol pharmacology and toxicology, careful extrapolation and interpretation of the BAC is needed, to justify an arrest and assignment of criminal liability. This review provides a summary of the pharmacokinetic properties of ethanol and the clinical effects of acute intoxication as they relate to common forensic questions. Concerns regarding the extrapolation of BAC and the implications of impaired memory caused by alcohol-induced blackouts are discussed. © 2017 American Academy of Psychiatry and the Law.

WHERE THE INDIVIDUAL MEETS THE ECOLOGICAL: A STUDY OF PARENT DRINKING PATTERNS, ALCOHOL OUTLETS AND CHILD PHYSICAL ABUSE

PubMed Central

Freisthler, Bridget; Gruenewald, Paul J.

2012-01-01

Background Despite well-known associations between heavy drinking and child physical abuse, little is known about specific risks related to drinking different amounts of alcohol in different drinking venues. This study uses a context specific dose-response model to examine how drinking in various venues (e.g., at bars or parties) are related to physically abusive parenting practices while controlling for individual and psychosocial characteristics. Methods Data were collected via a telephone survey of parents in 50 cities in California resulting in 2,163 respondents who reported drinking in the past year. Child physical abuse and corporal punishment were measured using the Conflict Tactics Scale, Parent Child version. Drinking behaviors were measured using continued drinking measures. Data were analyzed using zero inflated Poisson models. Results Drinking at homes, parties or bars more frequently was related to greater frequencies of physically abusive parenting practices. The use of greater amounts of alcohol in association with drinking at bars appeared to increase risks for corporal punishment, a dose-response effect. Dose-response relationships were not found for drinking at homes or parties or drinking at bars for physical abuse nor for drinking at home and parties for corporal punishment. Conclusion Frequencies of using drinking venues, particularly bars and home or parties, are associated with greater use of abusive parenting practices. These findings suggest that a parent’s routine drinking activities place children at different risks for being physically abused. They also suggest that interventions that take into account parents’ alcohol use at drinking venues are an important avenue for secondary prevention efforts. PMID:23316780

Risk of Salivary Gland Cancer After Childhood Cancer: A Report From the Childhood Cancer Survivor Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boukheris, Houda; Stovall, Marilyn; Gilbert, Ethel S.

Purpose: To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). Methods and Materials: Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. Results: During the time period of the study, 23 casesmore » of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. Conclusion: Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.« less

A Comparison Study of Quetiapine and Risperidone's Effectiveness and Safety on Treating Alcohol-induced Mental Disorder.

PubMed

Lv, Bei; Duan, Haishui

2016-08-25

Compared with Risperidone, Quetiapine's effectiveness and safety on treating alcohol-induced mental disorder is still unclear. To investigate the clinical effectiveness and safety of Quetiapine on treating alcohol-induced mental disorder. One hundred and forty-eight patients with alcohol-induced mental disorder were divided into the experimental group (75 patients) and the control group (73 patients) by the treatments they received. The patients in the experimental group were treated with Quetiapine by taking it three times per day orally. The mean (sd) maintenance dose was 151.2(27.3) mg/d, and the treatment cycle was 6 weeks. Patients in the control group received Risperidone once per day orally with a mean (sd) maintenance dose being 2.3(0.9) mg/d, and the treatment cycle was 6 weeks as well. The PANSS scale was used to assess patients' before and after treatment. The researchers also observed any adverse reactions in both treatment strategies and evaluated the effectiveness and safety of both treatment strategies. The mean (sd) PANSS scale score of the experimental group after two weeks of treatment was 71.9 (10.2), which was clearly better than the mean (sd) score before treatment (82.6 [11.4]), and was significantly better than the control group's mean (sd) score after two weeks (76.5[12.8]). Also, the experimental group's scores after 4 weeks of treatment and 6 weeks of treatment were significantly better than the control group. The experimental group's efficacy rate (94.7%) was higher than the control group's (90.4%); the cure rate of the experimental group (33.3%) was higher than that of the control group (24.7%), and the difference was statistically significant. The rates of adverse reactions in the experimental and control groups were 13.3% and 19.2% respectively, and they were significantly different from each other. Treating alcohol-induced mental disorder with Quetiapine is more effective than treating it with Risperidone. Quetiapine can improve patients' symptoms quickly, and lower the chance of adverse reactions. It is effective and safe.

Symptom-Triggered vs. Fixed-Dosing Management of Alcohol Withdrawal Syndrome.

PubMed

Skinner, Reagan T

2014-01-01

A literature review was conducted with the objective of creating evidence-based recommendations for use of symptom-triggered therapy (STT) or fixed-schedule dosing in treating alcohol withdrawal syndrome in inpatients. Use of STT reduced duration of therapy as well as the number of patients requiring treatment or medication, potentially reducing costs and risk of adverse medication reactions.

The enigma of 'harmful' alcohol consumption: evidence from a mixed methods study involving female drinkers in Scotland.

PubMed

Gill, Jan S; Rush, Robert; Black, Heather; O'May, Fiona P; Chick, Jonathan; Rees, Cheryl; McPake, Barbara

2016-01-01

An appreciation of the drinking patterns of population subgroups may usefully inform tailored interventions. For this purpose, research has highlighted a need to better describe the drinking behaviour of UK women. This study aims to characterise the purchasing and consumption behaviour of female heavy, harmed, drinkers in contact with Scottish health services in two cities and to explore the factors that influence the link to harm. Mixed methods study involving cross-sectional survey questionnaires and one-to-one interviews (5). The questionnaires documented (1) demographic data (including derived deprivation score), last week's (or 'typical' weekly) consumption (type, brand, volume, price, place of purchase), self-reported illnesses, and (2) Alcohol-Related Problem Questionnaire score. A total of 181 patients with serious health problems linked to alcohol were recruited within National Health Service (NHS) hospital clinics (in- and outpatient settings), in two Scottish cities during 2012. Median consumption was 157.6 UK units for the recorded week, with almost exclusive purchase from 'off-sale' retail outlets. Preferred drinks were white cider, vodka and white wine. Increasing problems was positively associated with drinking more in the week, being younger and belonging to Glasgow. For Scottish women, the current definition of 'harmful' consumption likely captures a fourfold variation in alcohol intake, with gender differences less apparent. While current alcohol-related harm is positively associated with dose and being younger, there is clear evidence of an influence of the less tangible 'Glasgow effect'. Future harm concerns are warranted by data relating to pattern, alcohol dose and cigarette use. © Royal Society for Public Health 2015.

Women’s Condom Use Assertiveness and Sexual Risk-Taking: Effects of Alcohol Intoxication and Adult Victimization

PubMed Central

Norris, Jeanette; George, William H.; Morrison, Diane M.; Zawacki, Tina; Davis, Kelly Cue; Hessler, Danielle M.

2008-01-01

This experiment examined relationships among adulthood victimization, sexual assertiveness, alcohol intoxication, and sexual risk-taking in female social drinkers (N = 161). Women completed measures of sexual assault and intimate partner violence history and sexual assertiveness before random assignment to 1 of 4 beverage conditions: control, placebo, low dose (.04%), or high dose (.08%). After drinking, women read a second-person story involving a sexual encounter with a new partner. As protagonist of the story, each woman rated her likelihood of condom insistence and unprotected sex. Victimization history and self-reported sexual assertiveness were negatively related. The less sexually assertive a woman was, the less she intended to insist on condom use, regardless of intoxication. By reducing the perceived health consequences of unprotected sex, intoxication indirectly decreased condom insistence and increased unprotected sex. Findings extend previous work by elucidating possible mechanisms of the relationship between alcohol and unprotected sex – perceived health consequences and situational condom insistence – and support the value of sexual assertiveness training to enhance condom insistence, especially since the latter relationship was robust to intoxication. PMID:18556139

Women's condom use assertiveness and sexual risk-taking: effects of alcohol intoxication and adult victimization.

PubMed

Stoner, Susan A; Norris, Jeanette; George, William H; Morrison, Diane M; Zawacki, Tina; Davis, Kelly Cue; Hessler, Danielle M

2008-09-01

This experiment examined relationships among adulthood victimization, sexual assertiveness, alcohol intoxication, and sexual risk-taking in female social drinkers (N=161). Women completed measures of sexual assault and intimate partner violence history and sexual assertiveness before random assignment to 1 of 4 beverage conditions: control, placebo, low dose (.04%), or high dose (.08%). After drinking, women read a second-person story involving a sexual encounter with a new partner. As protagonist of the story, each woman rated her likelihood of condom insistence and unprotected sex. Victimization history and self-reported sexual assertiveness were negatively related. The less sexually assertive a woman was, the less she intended to insist on condom use, regardless of intoxication. By reducing the perceived health consequences of unprotected sex, intoxication indirectly decreased condom insistence and increased unprotected sex. Findings extend previous work by elucidating possible mechanisms of the relationship between alcohol and unprotected sex - perceived health consequences and situational condom insistence - and support the value of sexual assertiveness training to enhance condom insistence, especially since the latter relationship was robust to intoxication.

How Do Alcohol and Relationship Type Affect Women’s Risk Judgment of Partners with Differing Risk Histories?

PubMed Central

Norris, Jeanette; Kiekel, Preston A.; Morrison, Diane M.; Davis, Kelly Cue; George, William H.; Zawacki, Tina; Abdallah, Devon Alisa; Jacques-Tiura, Angela J.; Stappenbeck, Cynthia A.

2013-01-01

Understanding how women judge male partners’ sexual risk is important to developing risk reduction programs. Applying a cognitive mediation model of sexual decision making, our study investigated effects of alcohol consumption (control, low dose, high dose) and relationship type (disrupted vs. new) on women’s risk judgments of a male sexual partner in three sexual risk conditions (low, unknown, high). After random assignment to an experimental condition, 328 participants projected themselves into a story depicting a sexual interaction. The story was paused to assess primary appraisals of sexual and relationship potential and secondary appraisals of pleasure, health, and relationship concerns, followed by sexual risk judgments. In all risk conditions, alcohol and disrupted relationship increased sexual potential whereas disrupted relationship increased relationship potential in the low- and high-risk conditions. In the unknown-risk condition, women in the no-alcohol, new relationship condition had the lowest primary sexual appraisals. In all conditions, sexual appraisals predicted all secondary appraisals, but primary relationship appraisals predicted only secondary relationship appraisals. Secondary health appraisals led to increased risk judgments whereas relationship appraisals predicted lower risk judgments. Possible intervention points include helping women to re-evaluate their safety beliefs about past partners, as well as to develop behavioral strategies for decreasing hazardous drinking. PMID:24003264

Alcohol consumption as a risk factor for tuberculosis: meta-analyses and burden of disease

PubMed Central

Shield, Kevin D.; Roerecke, Michael; Samokhvalov, Andriy V.; Lönnroth, Knut; Rehm, Jürgen

2017-01-01

Meta-analyses of alcohol use, alcohol dosage and alcohol-related problems as risk factors for tuberculosis incidence were undertaken. The global alcohol-attributable tuberculosis burden of disease was also re-estimated. Systematic searches were conducted, reference lists were reviewed and expert consultations were held to identify studies. Cohort and case-control studies were included if there were no temporal violations of exposure and outcome. Risk relations (RRs) were pooled by using categorical and dose-response meta-analyses. The alcohol-attributable tuberculosis burden of disease was estimated by using alcohol-attributable fractions. 36 of 1108 studies were included. RRs for alcohol use and alcohol-related problems were 1.35 (95% CI 1.09–1.68; I2: 83%) and 3.33 (95% CI 2.14–5.19; 87%), respectively. Concerning alcohol dosage, tuberculosis risk rose as ethanol intake increased, with evidence of a threshold effect. Alcohol consumption caused 22.02 incident cases (95% CI 19.70–40.77) and 2.35 deaths (95% CI 2.05–4.79) per 100 000 people from tuberculosis in 2014. Alcohol-attributable tuberculosis incidence increased between 2000 and 2014 in most high tuberculosis burden countries, whereas mortality decreased. Alcohol consumption was associated with an increased risk of tuberculosis in all meta-analyses. It was consequently a major contributor to the tuberculosis burden of disease. PMID:28705945

Alcohol ADME in primates studied with positron emission tomography.

PubMed

Li, Zizhong; Xu, Youwen; Warner, Don; Volkow, Nora D

2012-01-01

The sensitivity to the intoxicating effects of alcohol as well as its adverse medical consequences differ markedly among individuals, which reflects in part differences in alcohol's absorption, distribution, metabolism, and elimination (ADME) properties. The ADME of alcohol in the body and its relationship with alcohol's brain bioavailability, however, is not well understood. The ADME of C-11 labeled alcohol, CH(3) (11)CH(2)OH, 1 and C-11 and deuterium dual labeled alcohol, CH(3) (11)CD(2)OH, 2 in baboons was compared based on the principle that C-D bond is stronger than C-H bond, thus the reaction is slower if C-D bond breaking occurs in a rate-determining metabolic step. The following ADME parameters in peripheral organs and brain were derived from time activity curve (TAC) of positron emission tomography (PET) scans: peak uptake (C(max)); peak uptake time (T(max)), half-life of peak uptake (T(1/2)), the area under the curve (AUC(60 min)), and the residue uptake (C(60 min)). For 1 the highest uptake occurred in the kidney whereas for 2 it occurred in the liver. A deuterium isotope effect was observed in the kidneys in both animals studied and in the liver of one animal but not the other. The highest uptake for 1 and 2 in the brain was in striatum and cerebellum but 2 had higher uptake than 1 in all brain regions most evidently in thalamus and cingulate. Alcohol's brain uptake was significantly higher when given intravenously than when given orally and also when the animal was pretreated with a pharmacological dose of alcohol. The study shows that alcohol metabolism in peripheral organs had a large effect on alcohol's brain bioavailability. This study sets the stage for clinical investigation on how genetics, gender and alcohol abuse affect alcohol's ADME and its relationship to intoxication and medical consequences.

A meta-analysis of acute alcohol use and the risk of suicide attempt

PubMed Central

Borges, Guilherme; Bagge, Courtney; Cherpitel, Cheryl J.; Conner, Kenneth; Orozco, Ricardo; Rossow, Ingeborg

2016-01-01

Background While there are reviews reporting on the prevalence of acute use of alcohol (AUA) prior to suicide attempts, no review has used a meta-analytic approach to estimate common odds ratios (OR) of the effect of AUA on suicide attempts. We aim to report the results of the first meta-analysis of controlled epidemiological studies on acute alcohol use and suicide attempt. Methods The English language literature on Medline, PsychInfo, Google Scholar, and public-use databases was searched for original articles and critical review reports on acute alcohol use and suicide attempt for the period ranging from 1996–2015. Studies had to report an OR estimate for this association. Common odds ratios and 95% Confidence Intervals (95%CI) from random effects in meta-analyses for any acute alcohol use and 2 levels of alcohol use on suicide attempt were calculated. Results We gathered 7 studies that provided OR estimates for the likelihood of suicide attempt by acute alcohol use, compared to those who did not drink alcohol. Studies used case-control (3) and case-crossover design (4). All studies found increased ORs for acute alcohol use on suicide attempt. Meta-analysis revealed a common OR of 6.97 (95%CI=4.77, 10.17) for any acute alcohol use. Evidence from 4 studies suggests that «low levels of acute drinking» resulted in an OR of 2.71 (95%CI=1.56, 4.71) and «high levels» had much greater odds of suicide attempt, OR of 37.18 (95%CI=17.38, 79.53). Conclusions Acute use of alcohol is associated with increased likelihood of a suicide attempt, particularly at high doses. Such data should be incorporated into estimates of the burden of disease associated with alcohol use, which are currently limited by a consideration of only alcohol’s chronic effects. Future research should focus on the mechanisms through which acute use of alcohol confers risk for attempt. PMID:27928972

Optical absorption and thermally stimulated depolarization current studies of nickel chloride-doped poly(vinyl alcohol) irradiated with low-level fast neutron doses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abd El-Kader, F.H.; Ibrahim, S.S.; Attia, G.

1993-11-15

The influence of neutron irradiation on ultraviolet/visible absorption and thermally stimulated depolarization current in nickel chloride-poly(vinyl alcohol) (PVA) cast films has been investigated. The spectral measurements indicate the responsibility of the Ni[sup 2][sup +] ion in its octahedral symmetry. Dopant concentrations higher than 10 wt % NiCl[sub 2] are found to make the samples more resistant to a degradation effect caused by neutron irradiation. The thermally stimulated depolarization currents (TSDC) of pure PVA revealed the existence of the glass transition T[sub g] and space charge relaxation peaks, whereas doped-PVA samples show a new sub-T[sub g] relaxation peak. A proposed mechanismmore » is introduced to account for the neutron effects on both glass transition and space charge relaxation peaks. The peak positions, peak currents, and stored charges of the sub-T[sub g] relaxation peak are strongly affected by both the concentration of the dopant and neutron exposure doses.« less

Further characterization of the GlyT-1 inhibitor Org25935: anti-alcohol, neurobehavioral, and gene expression effects.

PubMed

Lidö, Helga Höifödt; Jonsson, Susanne; Hyytiä, Petri; Ericson, Mia; Söderpalm, Bo

2017-05-01

The glycine transporter-1 inhibitor Org25935 is a promising candidate in a treatment concept for alcohol use disorder targeting the glycine system. Org25935 inhibits ethanol-induced dopamine elevation in brain reward regions and reduces ethanol intake in Wistar rats. This study aimed to further characterise the compound and used ethanol consumption, behavioral measures, and gene expression as parameters to investigate the effects in Wistar rats and, as pharmacogenetic comparison, Alko-Alcohol (AA) rats. Animals were provided limited access to ethanol in a two-bottle free-choice paradigm with daily drug administration. Acute effects of Org25935 were estimated using locomotor activity and neurobehavioral status. Effects on gene expression in Wistar rats were measured with qPCR. The higher but not the lower dose of Org25935 reduced alcohol intake in Wistar rats. Unexpectedly, Org25935 reduced both ethanol and water intake and induced strong CNS-depressive effects in AA-rats (withdrawn from further studies). Neurobehavioral effects by Org25935 differed between the strains (AA-rats towards sedation). Org25935 did not affect gene expression at the mRNA level in the glycine system of Wistar rats. The data indicate a small therapeutic range for the anti-alcohol properties of Org25935, a finding that may guide further evaluations of the clinical utility of GlyT-1 inhibitors. The results point to the importance of pharmacogenetic considerations when developing drugs for alcohol-related medical concerns. Despite the lack of successful clinical outcomes, to date, the heterogeneity of drug action of Org25935 and similar agents and the unmet medical need justify further studies of glycinergic compounds in alcohol use disorder.

Treatment of alcoholic organic brain syndrome with the serotonin reuptake inhibitor fluvoxamine: a preliminary study.

PubMed

Stapleton, J M; Eckardt, M J; Martin, P; Adinoff, B; Roehrich, L; Bone, G; Rubinow, D; Linnoila, M

1988-01-01

The chronic effects of fluvoxamine (200 mg per day for 4 weeks) were studied in ten alcoholic organic brain syndrome patients in a double-blind cross-over design. Complete neuropsychological evaluation was performed as well as measurement of neurochemical changes in CSF. Fluvoxamine produced a small but significant improvement in memory performance. An analysis of fluvoxamine minus placebo difference scores showed a significant correlation between memory functioning and CSF 5HIAA levels. Alcohol amnestic syndrome patients who had the highest blood levels of fluvoxamine demonstrated the largest changes in CSF 5HIAA and improvement in memory performance under fluvoxamine. These findings implicate a role of serotonergic mechanisms in alcoholic organic brain syndrome and suggest that with individual titration of the drug dose, fluvoxamine might be a clinically useful agent in the treatment of this syndrome.

Adapting to alcohol: Dwarf hamster (Phodopus campbelli) ethanol consumption, sensitivity, and hoard fermentation.

PubMed

Lupfer, Gwen; Murphy, Eric S; Merculieff, Zoe; Radcliffe, Kori; Duddleston, Khrystyne N

2015-06-01

Ethanol consumption and sensitivity in many species are influenced by the frequency with which ethanol is encountered in their niches. In Experiment 1, dwarf hamsters (Phodopus campbelli) with ad libitum access to food and water consumed high amounts of unsweetened alcohol solutions. Their consumption of 15%, but not 30%, ethanol was reduced when they were fed a high-fat diet; a high carbohydrate diet did not affect ethanol consumption. In Experiment 2, intraperitoneal injections of ethanol caused significant dose-related motor impairment. Much larger doses administered orally, however, had no effect. In Experiment 3, ryegrass seeds, a common food source for wild dwarf hamsters, supported ethanol fermentation. Results of these experiments suggest that dwarf hamsters may have adapted to consume foods in which ethanol production naturally occurs. Copyright © 2015 Elsevier B.V. All rights reserved.

Different Hypothalamic Nicotinic α7 Receptor Expression and Response to Low Nicotine Dose in Alcohol-Preferring and Alcohol-Avoiding Rats.

PubMed

Nuutinen, Saara; Panula, Pertti; Salminen, Outi

2016-02-01

The aim of this study was to examine possible differences in nicotinic acetylcholine receptors and responses in rats with genetic preference or avoidance for alcohol. This was done by using 2 rat lines with high alcohol preference (Alko Alcohol [AA]) or alcohol avoidance (Alko Non-Alcohol [ANA]). Locomotor activity was measured following nicotine and histamine H3 receptor (H3R) antagonist treatment. In situ hybridization and receptor ligand binding experiments were used in drug-naïve animals to examine the expression of different α nicotinic receptor subunits. The AA rats were found to be more sensitive to the stimulatory effect of a low dose of nicotine than ANA rats, which were not significantly activated. Combination of histamine H3R antagonist, JNJ-39220675, and nicotine resulted to similar locomotor activation as nicotine alone. To further understand the mechanism underlying the difference in nicotine response in AA and ANA rats, we studied the expression of α5, α6, and α7 nicotinic receptor subunits in specific brain areas of AA and ANA rats. We found no differences in the expression of α5 nicotinic receptor subunits in the medial habenula and hippocampus or in α6 subunit in the ventral tegmental area and substantia nigra. However, the level of α7 nicotinic receptor subunit mRNA was significantly lower in the tuberomamillary nucleus of posterior hypothalamus of alcohol-preferring AA rats than in alcohol-avoiding ANA rats. Also the hypothalamic [125I-α-bungarotoxin binding was lower in AA rats indicating lower levels of α7 nicotinic receptors. The lower expression and receptor binding of α7 nicotinic receptors in the tuberomamillary nucleus of AA rats suggest a difference in the regulation of brain histamine neurons between the rat lines since the α7 nicotinic receptors are located in histaminergic neurons. Stronger nicotine-induced locomotor response, mediated partially via α7 receptors, and previously described high alcohol consumption in AA rats could be explained by the found difference in tuberomamillary α7 receptor levels. Copyright © 2016 by the Research Society on Alcoholism.

Central administration of the anorexigenic peptide neuromedin U decreases alcohol intake and attenuates alcohol-induced reward in rodents.

PubMed

Vallöf, Daniel; Ulenius, Lisa; Egecioglu, Emil; Engel, Jörgen A; Jerlhag, Elisabet

2017-05-01

By investigating the neurochemical mechanisms through which alcohol activates the brain reward systems, novel treatment strategies for alcohol use disorder (AUD), a chronic relapsing disease, can be developed. In contrast to the common view of the function of gut-brain peptides, such as neuromedin U (NMU), to regulate food intake and appetite, a novel role in reinforcement mediation has been implied. The anorexigenic effects of NMU are mediated via NMU2 receptors, preferably in the arcuate nucleus and paraventricular nucleus. The expression of NMU2 receptors is also expressed in several reward-related areas in the brain, suggesting a role in reward regulation. The present experiments were therefore set up to investigate the effect of intracerebroventricular administration of NMU on alcohol-mediated behaviors in rodents. We found that central administration of NMU attenuated alcohol-induced locomotor stimulation, accumbal dopamine release and the expression of conditioned place preference in mice. In addition, NMU dose dependently decreased alcohol intake in high, but not in low, alcohol-consuming rats. Central NMU administration did not alter the blood alcohol concentrations nor change the corticosterone levels in rodents. Given that AUD is a major health-care challenge causing an enormous cost to society and novel treatment strategies are warranted, our data suggest that NMU analogues deserve to be evaluated as novel treatment of AUD in humans. © 2016 The Authors Addiction Biology published by John Wiley & Sons Ltd.

Protective effect of Tribulus terrestris fruit extract on cerulein-induced acute pancreatitis in mice.

PubMed

Borran, Mina; Minaiyan, Mohsen; Zolfaghari, Behzad; Mahzouni, Parvin

2017-01-01

Antioxidant, anti-inflammatory, analgesic and antimicrobial activities of Tribulus terrestris ( T. terrestris ) could be helpful in the treatment of acute pancreatitis; thus, this study was designed to investigate the effects of T. terrestris on cerulein-induced acute pancreatitis in mice. Three doses (100, 200 and 400 mg/kg) of T. terrestris hydro-alcoholic extract were administered both orally (60 minutes before pancreatitis induction, p.o.) and intra-peritoneally (30 minutes before pancreatitis induction, i.p.) to different groups of mice (n=6). Pancreatitis was induced by five injections (i.p.) of cerulein 50μg/kg body weight with 1 hr intervals. Animals were euthanized 5 hr after the last injection of cerulein and tissue injures were assessed biochemically and pathologically. T. terrestris extract 200 and 400mg/kg (p.o.) and T. terrestris extract 400 mg/kg (i.p.) reduced pancreatic tissue myeloperoxidase (MPO) activity and serum amylase and lipase levels and alleviated histological parameters. These data suggest that T. terrestris hydro-alcoholic extract was effective in protecting against experimental acute pancreatitis and possibly the efficacy depends on dose and route of administration.

[Effect of alcohol on electrical organisation in the brain during a visuospatial working memory task and its relationship with the menstrual cycle].

PubMed

Sanz-Martin, Araceli; Hernández-González, Marisela; Guevara, Miguel Ángel; Santana, Gloria; Gumá-Díaz, Emilio

2014-02-01

The metabolism of alcohol and cognitive functions can vary during the menstrual cycle. Also, both alcohol ingestion and hormonal variations during menstruation have been associated with characteristic changes in electroencephalographic (EEG) activity. AIM. To determine whether EEG activity during a working memory task is affected by acute alcohol consumption, and if these EEG patterns vary in relation to different phases of the menstrual cycle. 24 women who drank a moderate dose of alcohol or placebo during the follicular and early luteal phases of the menstrual cycle. The EEG activity was recorded during performance of viso-spatial working memory task. Although the alcohol did not deteriorate the performance of working memory task, it caused in the EEG a decrease of relative theta power and lower right fronto-parietal correlation in theta and alpha2 bands. Only women who drank alcohol in the follicular phase had a higher relative potency of alpha1, which could indicate a lower level of arousal and attention. These results contribute to a better understanding of the brain mechanisms underlying cognitive changes with alcohol and its relationship to the menstrual cycle.

Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies

PubMed Central

Brien, Susan E; Ronksley, Paul E; Turner, Barbara J; Mukamal, Kenneth J

2011-01-01

Objective To systematically review interventional studies of the effects of alcohol consumption on 21 biological markers associated with risk of coronary heart disease in adults without known cardiovascular disease. Design Systematic review and meta-analysis. Data sources Medline (1950 to October 2009) and Embase (1980 to October 2009) without limits. Study selection Two reviewers independently selected studies that examined adults without known cardiovascular disease and that compared fasting levels of specific biological markers associated with coronary heart disease after alcohol use with those after a period of no alcohol use (controls). 4690 articles were screened for eligibility, the full texts of 124 studies reviewed, and 63 relevant articles selected. Results Of 63 eligible studies, 44 on 13 biomarkers were meta-analysed in fixed or random effects models. Quality was assessed by sensitivity analysis of studies grouped by design. Analyses were stratified by type of beverage (wine, beer, spirits). Alcohol significantly increased levels of high density lipoprotein cholesterol (pooled mean difference 0.094 mmol/L, 95% confidence interval 0.064 to 0.123), apolipoprotein A1 (0.101 g/L, 0.073 to 0.129), and adiponectin (0.56 mg/L, 0.39 to 0.72). Alcohol showed a dose-response relation with high density lipoprotein cholesterol (test for trend P=0.013). Alcohol decreased fibrinogen levels (−0.20 g/L, −0.29 to −0.11) but did not affect triglyceride levels. Results were similar for crossover and before and after studies, and across beverage types. Conclusions Favourable changes in several cardiovascular biomarkers (higher levels of high density lipoprotein cholesterol and adiponectin and lower levels of fibrinogen) provide indirect pathophysiological support for a protective effect of moderate alcohol use on coronary heart disease. PMID:21343206

The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice.

PubMed

Al Mansouri, Shamma; Ojha, Shreesh; Al Maamari, Elyazia; Al Ameri, Mouza; Nurulain, Syed M; Bahi, Amine

2014-09-01

Several recent studies have suggested that brain CB2 cannabinoid receptors play a major role in alcohol reward. In fact, the implication of cannabinoid neurotransmission in the reinforcing effects of ethanol (EtOH) is becoming increasingly evident. The CB2 receptor agonist, β-caryophyllene (BCP) was used to investigate the role of the CB2 receptors in mediating alcohol intake and ethanol-induced conditioned place preference (EtOH-CPP) and sensitivity in mice. The effect of BCP on alcohol intake was evaluated using the standard two-bottle choice drinking method. The mice were presented with increasing EtOH concentrations and its consumption was measured daily. Consumption of saccharin and quinine solutions was measured following the EtOH preference tests. Finally, the effect of BCP on alcohol reward and sensitivity was tested using an unbiased EtOH-CPP and loss of righting-reflex (LORR) procedures, respectively. BCP dose-dependently decreased alcohol consumption and preference. Additionally, BCP-injected mice did not show any difference from vehicle mice in total fluid intake in a 24-hour paradigm nor in their intake of graded concentrations of saccharin or quinine, suggesting that the CB2 receptor activation did not alter taste function. More importantly, BCP inhibited EtOH-CPP acquisition and exacerbated LORR duration. Interestingly, these effects were abrogated when mice were pre-injected with a selective CB2 receptor antagonist, AM630. Overall, the CB2 receptor system appears to be involved in alcohol dependence and sensitivity and may represent a potential pharmacological target for the treatment of alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

Medicinal Mushroom Cracked-Cap Polypore, Phellinus rimosus (Higher Basidiomycetes) Attenuates Acute Ethanol-Induced Lipid Peroxidation in Mice.

PubMed

Ajith, Thekkuttuparambil A; Janardhanan, Kainoor K

2015-01-01

Alcohol abuse and alcoholism remain one of the major health issues worldwide, especially in developing countries. The protective effect of Phellinus rimosus against acute alcohol-induced lipid peroxidation in the liver, kidney, and brain as well as its effect against antioxidant enzyme activity such as superoxide (SOD) and catalase (CAT) in the liver was evaluated in mice. Ethyl acetate extract of Ph. Rimosus (50 mg/kg body wt, p.o.) 1 h before each administration of alcohol (3 mL/kg, p.o.; total 2 doses at 24-h intervals) protected against lipid peroxidation in all organs and attenuated the decline of SOD and CAT activity in the liver. The fold increase in lipid peroxidation, including conjugated diene and thiobarbituric acid reactive substance (TBARS) levels, was highest in the liver. There were 2.6- and 1.5- fold increases in TBARS levels in the liver of the alcohol alone- and alcohol+Ph. Rimosus-treated groups, compared with that of the normal group. Activity of SOD and CAT in the liver of alcohol- and alcohol+Ph. Rimosus- treated animals was 9.05±1.38, 18.76±1.71, and 11.26±1.02, 31.58±3.35 IU/mg protein, respectively. Extract at 1 mg/mL inhibited 50.6% activity of aniline hydroxylase (CYP2E1) in liver homogenate. From these results, we concluded that the extract significantly protected against the lipid peroxidation. Protection in the liver may be due to the inhibitory effect on CYP2E1 as well as the direct radical scavenging effect of Ph. Rimosus, which warrants further research.

Chronic High Dose Alcohol Induces Osteopenia via Activation of mTOR Signaling in Bone Marrow Mesenchymal Stem Cells.

PubMed

Liu, Yao; Kou, Xiaoxing; Chen, Chider; Yu, Wenjing; Su, Yingying; Kim, Yong; Shi, Songtao; Liu, Yi

2016-08-01

Chronic consumption of excessive alcohol results in reduced bone mass, impaired bone structure, and increased risk of bone fracture. However, the mechanisms underlying alcohol-induced osteoporosis are not fully understood. Here, we show that high dose chronic alcohol consumption reduces osteogenic differentiation and enhances adipogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs), leading to osteopenia in a mouse model. Mechanistically, impaired osteo/adipogenic lineage differentiation of BMMSCs is due to activation of a phosphatidylinositide 3-kinase/AKT/mammalian target of rapamycin (mTOR) signaling cascade, resulting in downregulation of runt-related transcription factor 2 and upregulation of peroxisome proliferator-activated receptor gamma via activation of p70 ribosomal protein S6 kinase. Blockage of the mTOR pathway by rapamycin treatment ameliorates alcohol-induced osteopenia by rescuing impaired osteo/adipogenic lineage differentiation of BMMSCs. In this study, we identify a previously unknown mechanism by which alcohol impairs BMMSC lineage differentiation and reveal a potential rapamycin-based drug therapy for alcohol-induced osteoporosis. Stem Cells 2016;34:2157-2168. © 2016 AlphaMed Press.

Alcohol: impact on sports performance and recovery in male athletes.

PubMed

Barnes, Matthew J

2014-07-01

Alcohol is the most commonly used recreational drug globally and its consumption, often in large volume, is deeply embedded in many aspects of Western society. Indeed, athletes are not exempt from the influence alcohol has on society; they often consume greater volumes of alcohol through bingeing behaviour compared with the general population, yet it is often expected and recommended that athletes abstain from alcohol to avoid the negative impact this drug may have on recovery and sporting performance. While this recommendation may seem sensible, the impact alcohol has on recovery and sports performance is complicated and depends on many factors, including the timing of alcohol consumption post-exercise, recovery time required before recommencing training/competition, injury status and dose of alcohol being consumed. In general, acute alcohol consumption, at the levels often consumed by athletes, may negatively alter normal immunoendocrine function, blood flow and protein synthesis so that recovery from skeletal muscle injury may be impaired. Other factors related to recovery, such as rehydration and glycogen resynthesis, may be affected to a lesser extent. Those responsible for the wellbeing of athletes, including the athlete themselves, should carefully monitor habitual alcohol consumption so that the generic negative health and social outcomes associated with heavy alcohol use are avoided. Additionally, if athletes are to consume alcohol after sport/exercise, a dose of approximately 0.5 g/kg body weight is unlikely to impact most aspects of recovery and may therefore be recommended if alcohol is to be consumed during this period.

Increased preference for ethanol in the infant rat after prenatal ethanol exposure, expressed on intake and taste reactivity tests.

PubMed

Arias, Carlos; Chotro, M Gabriela

2005-03-01

Previous studies have shown that prenatal exposure during gestational days 17 to 20 to low or moderate doses of ethanol (1 or 2 g/kg) increases alcohol intake in infant rats. Taking into account that higher consumption does not necessarily suggest a preference for alcohol, in the present study, the hedonic nature of the prenatal experience was analyzed further with the use of a taste reactivity test. General activity, wall climbing, passive drips, paw licking, and mouthing in response to intraoral infusions of alcohol, water, and a sucrose-quinine solution (which resembles alcohol taste in rats) were tested in 161 preweanling 14-day-old rat pups that were prenatally exposed to 0, 1, or 2 g/kg of alcohol during gestational days 17 to 20. Consumption of those substances was measured during the taste reactivity test and on postnatal day 15. Pups that were prenatally exposed to both doses of ethanol displayed lower levels of general activity and wall climbing than controls in response to ethanol. Infant rats that were treated prenatally with both doses of ethanol showed higher intake of the drug and also more mouthing and paw licking in response to ethanol taste. Only pups that were exposed to the higher ethanol dose in utero generalized those responses to the sucrose-quinine compound. These results seem to indicate that for the infant rat, the palatability of ethanol is enhanced after exposure to the drug during the last days of gestation.

Alcohol consumption among first-time mothers and the risk of preterm birth: a cohort study.

PubMed

Dale, Maria T G; Bakketeig, Leiv S; Magnus, Per

2016-04-01

Our aim was to explore the association between alcohol consumption, before and during pregnancy, and the risk of preterm birth among 46,252 primiparous mothers. We obtained information on alcohol consumption from questionnaire responses at pregnancy week 15 from the prospective, observational Norwegian Mother and Child Cohort Study. Data on preterm birth, categorized as delivery before gestation week 37, were retrieved from the Medical Birth Registry of Norway. Among the participants, 91% consumed alcohol before pregnancy and fewer than 20% reported consuming alcohol during pregnancy. The adjusted odds ratio (aOR) for preterm birth associated with prepregnancy alcohol consumption was 0.81 (95% confidence interval [CI], 0.70-0.95). We did not find a risk reduction for overall drinking during pregnancy, aOR = 1.03 (95% CI, 0.90-1.19). However, dose-response analyses showed tendencies toward adverse effects when drinking 1-3 times per month during the first 15 weeks of pregnancy, aOR = 1.51 (95% CI, 1.14-2.00). We did not find any effects of alcohol consumption during pregnancy, whereas pre-pregnancy drinking was associated with reduced risk of preterm birth. Residual confounding may have influenced the risk estimates, especially before pregnancy, as nondrinkers have lower socioeconomic status and well-being than drinkers. Copyright © 2016 Elsevier Inc. All rights reserved.

A Preliminary Investigation of Individual Differences in Subjective Responses to D-Amphetamine, Alcohol, and Delta-9-Tetrahydrocannabinol Using a Within-Subjects Randomized Trial

PubMed Central

Wardle, Margaret C.; Marcus, Benjamin A.; de Wit, Harriet

2015-01-01

Polydrug use is common, and might occur because certain individuals experience positive effects from several different drugs during early stages of use. This study examined individual differences in subjective responses to single oral doses of d-amphetamine, alcohol, and delta-9-tetrahydrocannabinol (THC) in healthy social drinkers. Each of these drugs produces feelings of well-being in at least some individuals, and we hypothesized that subjective responses to these drugs would be positively correlated. We also examined participants’ drug responses in relation to personality traits associated with drug use. In this initial, exploratory study, 24 healthy, light drug users (12 male, 12 female), aged 21–31 years, participated in a fully within-subject, randomized, counterbalanced design with six 5.5-hour sessions in which they received d-amphetamine (20mg), alcohol (0.8 g/kg), or THC (7.5 mg), each paired with a placebo session. Participants rated the drugs’ effects on both global measures (e.g. feeling a drug effect at all) and drug-specific measures. In general, participants’ responses to the three drugs were unrelated. Unexpectedly, “wanting more” alcohol was inversely correlated with “wanting more” THC. Additionally, in women, but not in men, “disliking” alcohol was negatively correlated with “disliking” THC. Positive alcohol and amphetamine responses were related, but only in individuals who experienced a stimulant effect of alcohol. Finally, high trait constraint (or lack of impulsivity) was associated with lower reports of liking alcohol. No personality traits predicted responses across multiple drug types. Generally, these findings do not support the idea that certain individuals experience greater positive effects across multiple drug classes, but instead provide some evidence for a “drug of choice” model, in which individuals respond positively to certain classes of drugs that share similar subjective effects, and dislike other types of drugs. Trial Registration ClinicalTrials.gov NCT02485158 PMID:26513587

A 14-day repeated-dose oral toxicological evaluation of an isothiocyanate-enriched hydro-alcoholic extract from Moringa oleifera Lam. seeds in rats.

PubMed

Kim, Youjin; Jaja-Chimedza, Asha; Merrill, Daniel; Mendes, Odete; Raskin, Ilya

2018-01-01

A 14-d short-term oral toxicity study in rats evaluated the safety of moringa isothiocyanate-1 (MIC-1)-enriched hydro-alcoholic moringa seeds extract (MSE). Rats (5 males/5 females per group) were gavaged daily for 14 d with the vehicle control or MSE, at 78 (low), 257 (mid-low), 772 (mid-high), or 2571 (high) mg/kg bw/d, standardized to MIC-1 (30, 100, 300, or 1000 mg/kg bw/d, respectively). Toxicological endpoints included body weight and weight gain, food consumption and feed efficiency, clinical observations, hematology, gross necropsy and histopathology, and relative organ weights. Mortality was only observed in the high dose group animals, both male and female, representing decreases in body weight/weight gain and food consumption/feed efficiency. Irregular respiratory patterns and piloerection were major clinical observations found primarily in the mid-high and high dose group animals. In the high dose group, gastrointestinal distention and stomach discoloration were observed in non-surviving males and females, and degeneration and necrosis of the testicular germinal cells and epididymal cells were also observed in a non-surviving male. Increased liver weights were found in females in the mid-high and high dose groups. Animals in the low and mid-low groups did not exhibit adverse effects of MSE (100 mg/kg bw/d MIC-1). A no observed adverse effect level (NOAEL) of the standardized MSE was determined as 257 mg/kg bw/d providing 100 mg/kg bw/d MIC-1.

A comparison of standard inhalers for asthma with and without alcohol as the propellant on the measurement of alcohol in breath.

PubMed

Ignacio-García, José M; Ignacio-García, Juan M; Almenara-Barrios, José; Chocrón-Giraldez, María J; Hita-Iglesias, Carmen

2005-01-01

Because most bronchodilator inhalers contain propellant gases or a small amount of ethanol as a co-solvent, the potential for these products to generate false readings on a evidential breath alcohol instrument was evaluated in 69 volunteers with clinically stable asthma. All subjects underwent a breath test on an infrared breath alcohol analyzer (Alcotest 7110, Dräger, Lübeck, Germany) before the use of the asthma inhaler and 1 and 5 min after inhalation. The effects of antiasthmatic medications delivered by metered dose inhalers (MDIs) with alcohol as a vehicle, alcohol-free MDIs, and dry powder inhalers were assessed in homogeneous groups of four to five patients. All subjects were alcohol-free on the preliminary breath test. One minute after inhalation, negative readings were only observed in 25 (36.2%) of subjects. In 62.3% of patients, apparent alcohol results were considered interferences or unstable readings by the breath-test instrument. One subject showed a final positive breath alcohol level (0.07 mg/L). After the use of dry powder inhalers, valid results without interferences were obtained. However, 89.6% of patients in which bronchodilators were delivered by MDIs (with propellant gases in the aerosol) showed altered partial readings and labeled the final output as "invalid," but tests performed 5 min after the use of inhalers were valid and correct in all cases. MDIs with propellants as a vehicle may cause false positive breath alcohol readings in some patients. These effects are transient and may be prevented by a 5-10-min interval between the use of MDIs and breath alcohol testing.

Mining the nucleus accumbens proteome for novel targets of alcohol self-administration in male C57BL/6J mice.

PubMed

Faccidomo, Sara; Swaim, Katarina S; Saunders, Briana L; Santanam, Taruni S; Taylor, Seth M; Kim, Michelle; Reid, Grant T; Eastman, Vallari R; Hodge, Clyde W

2018-06-01

There is a clear need for discovery of effective medications to treat behavioral pathologies associated with alcohol addiction, such as chronic drinking. The goal of this preclinical study was to assess effects of chronic alcohol drinking on the nucleus accumbens (NAcb) proteome to identify and validate novel targets for medications development. Two-dimensional difference in-gel electrophoresis (2D-DIGE) with matrix-assisted laser desorption ionization tandem time-of-flight (MALDI-TOF/TOF) was used to assess effects of chronic voluntary home-cage (24-h access) alcohol drinking on the NAcb proteome of C57BL/6J mice. To extend these findings to a model of alcohol self-administration and reinforcement, we investigated potential regulation of the positive reinforcing effects of alcohol by the target protein glutathione S-transferase Pi 1 (GSTP1) using a pharmacological inhibition strategy in mice trained to self-administer alcohol or sucrose. Expression of 52 unique proteins in the NAcb was changed by chronic alcohol drinking relative to water control (23 upregulated, 29 downregulated). Ingenuity Pathway Analysis showed that alcohol drinking altered an array of protein networks associated with neurological and psychological disorders, molecular and cellular functions, and physiological systems and development. DAVID functional annotation analysis identified 9 proteins (SNCA, GSTP1, PRDX3, PPP3R1, EIF5A, PHB, PEBP1/RKIP, GAPDH, AND SOD1) that were significantly overrepresented in a functional cluster that included the Gene Ontology categories "response to alcohol" and "aging." Immunoblots confirmed changes in Pebp1 (RKIP) and GSTP1 in NAcb with no change in amygdala or frontal cortex, suggesting anatomical specificity. Systemic inhibition of GSTP1 with Ezatiostat (0-30 mg/kg, i.p.) dose-dependently reduced the reinforcing effects of alcohol as measured by operant self-administration, in the absence of motor effects. Sucrose self-administration was also reduced but in a manner associated with nonspecific motor inhibition. Protein expression profiling identified an array of proteins and networks in the NAcb, including GSTP1, that are novel molecular targets of chronic alcohol drinking. Pharmacological inhibition of GSTP1 significantly reduced the positive reinforcing effects of alcohol, which regulate repetitive use and abuse liability. The observation that this protein was both upregulated after chronic drinking and that its inhibition could modulate the reinforcing properties of alcohol suggests that it is a key target for alcohol-related pathologies. Proteomic strategies combined with specific preclinical models has potential to identify and validate novel targets of alcohol that may be useful in the medical management of alcohol addiction.

Radiation sensitive indicator based on tetrabromophenol blue dyed poly(vinyl alcohol)

NASA Astrophysics Data System (ADS)

Beshir, W. B.

2013-05-01

Radiation sensitive indicators based on dyed polyvinyl alcohol (PVA) containing acid- sensitive dye (tetrabromophenol blue, TBPB) and chloral hydrate (CCl3·CH·(OH)2, 2,2,2-trichloroethane-1,1-diol) have been developed. These plastic film dosimeters undergo color change from blue (the alkaline form of TBPB) to yellow (the acidic form of TBPB), indicating acid formation. The concentration of radiation formed acids in the films containing different concentrations of chloral hydrate was calculated at different doses. These films can be used as dosimeters for food irradiation applications where the maximum of the useful dose ranges are between 1 and 8 kGy depending on chloral hydrate concentration in the film. The films have the advantage of negligible humidity effects on response in the intermediate range of relative humidity from 0 to 70% as good post irradiation stability when stored in the dark at room temperature. The overall combined uncertainty (at 2σ) associated with measurement of response (ΔA mm-1) at 623 nm for dose range 1-8 kGy is 4.53%.

Are there any potentially dangerous pharmacological effects of combining ADHD medication with alcohol and drugs of abuse? A systematic review of the literature.

PubMed

Barkla, Xanthe M; McArdle, Paul A; Newbury-Birch, Dorothy

2015-10-30

Among young people up to 18 years of age, approximately 5% have attention deficit hyperactivity disorder (ADHD), many of whom have symptoms persisting into adulthood. ADHD is associated with increased risk of co-morbid psychiatric disorders, including substance misuse. Many will be prescribed medication, namely methylphenidate, atomoxetine, dexamphetamine and lisdexamfetamine. If so, it is important to know if interactions exist and if they are potentially toxic. Three databases (Medline, EMBASE and PsychINFO) from a 22 year period (1992 - June 2014) were searched systematically. Key search terms included alcohol, substance related disorders, methylphenidate, atomoxetine, dexamphetamine, lisdexamfetamine, and death, which identified 493 citations (344 after removal of duplicates). The eligibility of each study was assessed jointly by two investigators, leaving 20 relevant articles. We identified only a minimal increase in side-effects when ADHD medication (therapeutic doses) was taken with alcohol. None of the reviewed studies showed severe sequelae among those who had overdosed on ADHD medication and other coingestants, including alcohol. The numbers across all the papers studied remain too low to exclude uncommon effects. Also, studies of combined effects with novel psychoactive substances have not yet appeared in the literature. Nevertheless, no serious sequelae were identified from combining ADHD medication with alcohol/illicit substances from the pre-novel psychoactive substance era.

Effects of naltrexone and LY255582 on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats.

PubMed

Dhaher, Ronnie; Toalston, Jamie E; Hauser, Sheketha R; Bell, Richard L; McKinzie, David L; McBride, William J; Rodd, Zachary A

2012-02-01

Research indicates opioid antagonists can reduce alcohol drinking in rodents. However, tests examining the effects of opioid antagonists on ethanol seeking and relapse behavior have been limited. The present study examined the effects of two opioid antagonists on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats. Adult P rats were self-trained in two-lever operant chambers to self-administer 15% (vol/vol) ethanol on a fixed-ratio 5 (FR5) versus water on a FR1 concurrent schedule of reinforcement in daily 1-h sessions. After 10 weeks, rats underwent extinction training, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without ethanol or water to measure responses on the ethanol and water levers for four sessions. After a subsequent 2 weeks in the home cage, without access to ethanol, rats were returned to the operant chambers with ethanol and water available. Effects of antagonists on maintenance responding were tested after several weeks of daily 1-h sessions. Naltrexone (NAL; 1-10mg/kg, subcutaneously [s.c.]; n=8/dose), LY255582 (LY; 0.03-1mg/kg, s.c.; n=8/dose), or vehicle were injected 30min before the first session (in the absence of ethanol), following 2 weeks in their home cages, and for four consecutive sessions of ethanol self-administration under maintenance and relapse conditions. Both NAL and LY reduced responses on the ethanol lever without any fluids present, and ethanol self-administration under relapse and on-going drinking conditions, with LY being more potent than NAL. Both NAL and LY were less effective in reducing responding in the absence of ethanol than in reducing ethanol self-administration. Overall, the results indicate that the opioid system is involved in mediating ethanol seeking, and ethanol self-administration under relapse and on-going alcohol drinking, but that different neurocircuits may underlie these behaviors. Published by Elsevier Inc.

Effects of Litchi chinensis fruit isolates on prostaglandin E2 and nitric oxide production in J774 murine macrophage cells

PubMed Central

2012-01-01

Background Litchi chinensis is regarded as one of the 'heating' fruits in China, which causes serious inflammation symptoms to people. Methods In the current study, the effects of isolates of litchi on prostaglandin E2 (PGE2) and nitric oxide (NO) production in J774 murine macrophage cells were investigated. Results The AcOEt extract (EAE) of litchi was found effective on stimulating PGE2 production, and three compounds, benzyl alcohol, hydrobenzoin and 5-hydroxymethyl-2-furfurolaldehyde (5-HMF), were isolated and identified from the EAE. Benzyl alcohol caused markedly increase in PGE2 and NO production, compared with lipopolysaccharide (LPS) as positive control, and in a dose-dependent manner. Hydrobenzoin and 5-HMF were found in litchi for the first time, and both of them stimulated PGE2 and NO production moderately in a dose-dependent manner. Besides, regulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNA expression and NF-κB (p50) activation might be involved in mechanism of the stimulative process. Conclusion The study showed, some short molecular compounds in litchi play inflammatory effects on human. PMID:22380404

The effectiveness of an intervention to reduce alcohol‐related violence in premises licensed for the sale and on‐site consumption of alcohol: a randomized controlled trial

PubMed Central

Alam, M. Fasihul; Heikkinen, Marjukka; Hood, Kerenza; Huang, Chao; Moore, Laurence; Murphy, Simon; Playle, Rebecca; Shepherd, Jonathan; Shovelton, Claire; Sivarajasingam, Vaseekaran; Williams, Anne

2017-01-01

Abstract Background and Aims Premises licensed for the sale and consumption of alcohol can contribute to levels of assault‐related injury through poor operational practices that, if addressed, could reduce violence. We tested the real‐world effectiveness of an intervention designed to change premises operation, whether any intervention effect changed over time, and the effect of intervention dose. Design A parallel randomized controlled trial with the unit of allocation and outcomes measured at the level of individual premises. Setting All premises (public houses, nightclubs or hotels with a public bar) in Wales, UK. Participants A randomly selected subsample (n = 600) of eligible premises (that had one or more violent incidents recorded in police‐recorded crime data; n = 837) were randomized into control and intervention groups. Intervention and comparator Intervention premises were audited by Environmental Health Practitioners who identified risks for violence and provided feedback by varying dose (informal, through written advice, follow‐up visits) on how risks could be addressed. Control premises received usual practice. Measurements Police data were used to derive a binary variable describing whether, on each day premises were open, one or more violent incidents were evident over a 455‐day period following randomization. Findings Due to premises being unavailable at the time of intervention delivery 208 received the intervention and 245 were subject to usual practice in an intention‐to‐treat analysis. The intervention was associated with an increase in police recorded violence compared to normal practice (hazard ratio = 1.34, 95% confidence interval = 1.20–1.51). Exploratory analyses suggested that reduced violence was associated with greater intervention dose (follow‐up visits). Conclusion An Environmental Health Practitioner‐led intervention in premises licensed for the sale and on‐site consumption of alcohol resulted in an increase in police recorded violence. PMID:28543914

Serotonin-3 receptors in the posterior ventral tegmental area regulate ethanol self-administration of alcohol-preferring (P) rats.

PubMed

Rodd, Zachary A; Bell, Richard L; Oster, Scott M; Toalston, Jamie E; Pommer, Tylene J; McBride, William J; Murphy, James M

2010-05-01

Several studies indicated the involvement of serotonin-3 ([5-hydroxy tryptamine] 5-HT(3)) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT(3) receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers (Coulbourn Instruments, Allentown, PA) were used to examine the effects of seven consecutive bilateral microinfusions of ICS 205-930 (ICS), a 5-HT(3) receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (vol/vol) ethanol self-administration. P rats readily acquired ethanol self-administration by the fourth session. The three highest doses (0.125, 0.25, and 1.25 microg) of ICS prevented acquisition of ethanol self-administration. During the acquisition postinjection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the three highest doses (0.75, 1.0, and 1.25 microg) of ICS significantly increased responding on the ethanol lever; after the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Microinfusion of ICS into the posterior VTA did not alter the low responding on the water lever and did not alter saccharin (0.0125% wt/v) self-administration. Microinfusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT(3) receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration and/or repeated treatments with a 5-HT(3) receptor antagonist may alter neuronal circuitry within the posterior VTA. 2010 Elsevier Inc. All rights reserved.

Alcohol Attenuates Load-related Activation During a Working Memory Task: Relation to Level of Response to Alcohol

PubMed Central

Paulus, Martin P.; Tapert, Susan F.; Pulido, Carmen; Schuckit, Marc A.

2008-01-01

Background A low level of response to alcohol is a major risk factor for the development of alcohol dependence, but neural correlates of this marker are unclear. Method Ten healthy volunteers were classified by median split on level of response to alcohol and underwent 2 sessions of functional magnetic resonance imaging following ingestion of a moderate dose of alcohol and a placebo. The blood oxygen level–dependent activation to an event-related visual working memory test was examined. Results The subjects exhibited longer response latencies and more errors as a function of increasing working memory load and showed a load-dependent increase in activation in dorsolateral prefrontal cortex, posterior parietal cortex, and visual cortex. Alcohol did not affect performance (errors or response latency), but attenuated the working memory load–dependent activation in the dorsolateral prefrontal cortex. During the placebo condition, individuals with a low level of response to alcohol showed greater activation in dorsolateral prefrontal cortex and posterior parietal cortex than those with a high level of response to alcohol. During the alcohol condition, groups showed similar attenuation of load-dependent brain activation in these regions. Conclusion Low-level responders relative to high-level responders exhibited an increased working memory load–dependent activation in dorsolateral prefrontal cortex and posterior parietal cortex when not exposed to alcohol. This increase in brain response was attenuated in low-level responders after ingesting a moderate dose of alcohol. PMID:16899039

Novice drivers' performance after different alcohol dosages and placebo in the divided-attention steering simulator (DASS).

PubMed

Verster, Joris C; Wester, Anne E; Goorden, Maartje; van Wieringen, Jan-Peter; Olivier, Berend; Volkerts, Edmund R

2009-05-01

The divided-attention steering simulator (DASS) is designed to measure lane-keeping (i.e., a tracking task using a steering wheel) while performing a secondary visual task (responding to digits that appear in the corners of the computer screen). Some studies have already used the DASS, but the magnitude of impairment is difficult to interpret because reference values are lacking. To examine the magnitude of impairment after administration of four different dosages of alcohol and placebo. Thirty-two healthy young adults participated in this randomized, single-blind crossover trial. Subjects received alcohol to gain a blood alcohol concentration (BAC) of 0.02%, 0.05%, 0.08%, and 0.10% or alcohol-placebo. Sixteen subjects performed a 30-min test in DASS (dual-task condition). Outcome measures were steering error, reaction time, and percentage of errors. Sixteen other subjects performed the test without performing the secondary peripheral task (single-task condition). Twenty-eight subjects (novice drivers; drivers' license up to 5 years) were included in the analyses. Dose-dependent impairment was found in both the single-task condition (F ((4,11)) = 10.86, p < 0.001) and the dual-task condition (F ((4,9)) = 5.58, p < 0.015). Performance at all BAC levels differed significantly (p < 0.05) from alcohol-placebo, except BAC 0.02%. With increasing BAC levels, subjects made more errors and reacted slower on the peripheral visual search task, but these effects did not reach significance. With increasing BAC, dose-dependent impairment was found. The DASS seems to be a suitable divided-attention task that is useful in psychopharmacological research and training of novice drivers.

Nicotine enhances the locomotor stimulating but not the conditioned rewarding effect of ethanol in DBA/2J mice.

PubMed

Gubner, Noah R; Cunningham, Christopher L; Phillips, Tamara J

2015-01-01

One hypothesis to explain the high rate of nicotine and alcohol (ethanol [EtOH]) co-abuse is that these drugs have enhanced rewarding effects when taken together. The goal of this work was to use the conditioned place preference (CPP) procedure to determine whether nicotine would enhance the development of EtOH-induced CPP. The conditioned rewarding effects of nicotine (1 or 2 mg/kg of nicotine tartrate), EtOH (1 g/kg), and nicotine plus EtOH in combination were assessed using a well-established CPP procedure chosen specifically for examining alterations in the development of EtOH-induced CPP by nicotine. In addition, the reference dose procedure was used to directly compare the conditioned rewarding effect of EtOH versus nicotine plus EtOH. DBA/2J mice were used because they are an inbred strain that has repeatedly been shown to develop CPP to EtOH. Neither dose of nicotine alone produced CPP, whereas EtOH did, using the standard EtOH CPP procedure. The magnitude of EtOH-induced CPP was not affected by co-administration of 1 mg/kg nicotine, but 2 mg/kg nicotine interfered with the development of EtOH-induced CPP. Using the reference dose procedure, there was no significant preference or aversion for either nicotine + EtOH dose combination versus EtOH alone. However, combined nicotine and EtOH had a larger effect on locomotor activity, during the conditioning trials, compared to their additive effect when given alone, consistent with previous data. These data do not support the hypothesis that nicotine enhances the conditioned rewarding effect of EtOH. This finding differs from the combined locomotor stimulant effects of nicotine and EtOH that were observed in this study and in our previously published work, and suggests that combined stimulant effects of nicotine and EtOH do not predict enhanced reward. Copyright © 2015 by the Research Society on Alcoholism.

Developing measures of fatigue using an alcohol comparison to validate the effects of fatigue on performance.

PubMed

Williamson, A M; Feyer, A M; Mattick, R P; Friswell, R; Finlay-Brown, S

2001-05-01

The effects of 28 h of sleep deprivation were compared with varying doses of alcohol up to 0.1% blood alcohol concentration (BAC) in the same subjects. The study was conducted in the laboratory. Twenty long-haul truck drivers and 19 people not employed as professional drivers acted as subjects. Tests were selected that were likely to be affected by fatigue, including simple reaction time, unstable tracking, dual task, Mackworth clock vigilance test, symbol digit coding, visual search, sequential spatial memory and logical reasoning. While performance effects were seen due to alcohol for all tests, sleep deprivation affected performance on most tests, but had no effect on performance on the visual search and logical reasoning tests. Some tests showed evidence of a circadian rhythm effect on performance, in particular, simple reaction time, dual task, Mackworth clock vigilance, and symbol digit coding, but only for response speed and not response accuracy. Drivers were slower but more accurate than controls on the symbol digit test, suggesting that they took a more conservative approach to performance of this test. This study demonstrated which tests are most sensitive to sleep deprivation and fatigue. The study therefore has established a set of tests that can be used in evaluations of fatigue and fatigue countermeasures.

Alcohol drinking and esophageal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population.

PubMed

Oze, Isao; Matsuo, Keitaro; Wakai, Kenji; Nagata, Chisato; Mizoue, Tetsuya; Tanaka, Keitaro; Tsuji, Ichiro; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro

2011-05-01

Although alcohol drinking is considered as an important risk factor for esophageal cancer, the magnitude of the association might be varied among geographic areas. Therefore, we reviewed epidemiologic studies on the association between alcohol drinking and esophageal cancer among the Japanese population. Original data were obtained from MEDLINE, searched using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient') and the magnitude of association ('strong', 'moderate', 'weak' or 'no association'), together with biological plausibility as previously evaluated by the International Agency of Research on Cancer. We identified four cohort studies and nine case-control studies. All cohort studies and case-control studies showed strong positive associations between esophageal cancer and alcohol drinking. All cohort studies and six case-control studies showed that alcohol drinking had the dose- or frequency-response relationships with esophageal cancer. In addition, four case-control studies showed that acetaldehyde dehydrogenase Glu504Lys polymorphism had strong effect modification with alcohol drinking. We conclude that there is convincing evidence that alcohol drinking increases the risk of esophageal cancer in the Japanese population.

Distraction produces over-additive increases in the degree to which alcohol impairs driving performance.

PubMed

Van Dyke, Nicholas A; Fillmore, Mark T

2015-12-01

Research indicates that alcohol intoxication and increased demands on drivers' attention from distractions (e.g., passengers and cell phones) contribute to poor driving performance and increased rates of traffic accidents and fatalities. The present study examined the separate and combined effects of alcohol and distraction on simulated driving performance at blood alcohol concentrations (BrACs) below the legal driving limit in the USA (i.e., 0.08 %). Fifty healthy adult drivers (36 men and 14 women) were tested in a driving simulator following a 0.65-g/kg dose of alcohol and a placebo. Drivers completed two drive tests: a distracted drive, which included a two-choice detection task, and an undistracted control drive. Multiple indicators of driving performance, such as drive speed, within-lane deviation, steering rate, and lane exceedances were measured. Alcohol and distraction each impaired measures of driving performance. Moreover, the magnitude of alcohol impairment was increased by at least twofold when tested under the distracting versus the undistracted condition. The findings highlight the need for a clearer understanding of how common distractions impact intoxicated drivers, especially at BrACs that are currently legal for driving in the USA.

Subjective aggression during alcohol and cannabis intoxication before and after aggression exposure.

PubMed

De Sousa Fernandes Perna, E B; Theunissen, E L; Kuypers, K P C; Toennes, S W; Ramaekers, J G

2016-09-01

Alcohol and cannabis use have been implicated in aggression. Alcohol consumption is known to facilitate aggression, whereas a causal link between cannabis and aggression has not been clearly demonstrated. This study investigated the acute effects of alcohol and cannabis on subjective aggression in alcohol and cannabis users, respectively, following aggression exposure. Drug-free controls served as a reference. It was hypothesized that aggression exposure would increase subjective aggression in alcohol users during alcohol intoxication, whereas it was expected to decrease subjective aggression in cannabis users during cannabis intoxication. Heavy alcohol (n = 20) and regular cannabis users (n = 21), and controls (n = 20) were included in a mixed factorial study. Alcohol and cannabis users received single doses of alcohol and placebo or cannabis and placebo, respectively. Subjective aggression was assessed before and after aggression exposure consisting of administrations of the point-subtraction aggression paradigm (PSAP) and the single category implicit association test (SC-IAT). Testosterone and cortisol levels in response to alcohol/cannabis treatment and aggression exposure were recorded as secondary outcome measures. Subjective aggression significantly increased following aggression exposure in all groups while being sober. Alcohol intoxication increased subjective aggression whereas cannabis decreased the subjective aggression following aggression exposure. Aggressive responses during the PSAP increased following alcohol and decreased following cannabis relative to placebo. Changes in aggressive feeling or response were not correlated to the neuroendocrine response to treatments. It is concluded that alcohol facilitates feelings of aggression whereas cannabis diminishes aggressive feelings in heavy alcohol and regular cannabis users, respectively.

Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people.

PubMed

Myrick, Hugh; Anton, Raymond F; Li, Xingbao; Henderson, Scott; Randall, Patrick K; Voronin, Konstantin

2008-04-01

Medication for the treatment of alcoholism is currently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence. To explore the effect of naltrexone, ondansetron hydrochloride, or the combination of these medications on cue-induced craving and ventral striatum activation. Functional brain imaging was conducted during alcohol cue presentation. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute. Ninety non-treatment-seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (< 14 drinks per week) paid volunteers recruited through advertisements at an academic center. A taste of alcohol and a series of alcohol-related pictures, neutral beverage pictures, and visual control images were provided to volunteers after 7 days of double-blind randomly assigned daily dosing with 50 mg of naltrexone (n = 23), 0.50 mg of ondansetron hydrochloride (n = 23), the combination of the 2 medications (n = 20), or matching placebos (n = 24). Difference in brain blood oxygen level-dependent magnetic resonance when viewing alcohol pictures vs neutral beverage pictures with a particular focus on ventral striatum activity comparison across medication groups. Self-ratings of alcohol craving. The combination treatment decreased craving for alcohol. Naltrexone with (P = .02) or without (P = .049) ondansetron decreased alcohol cue-induced activation of the ventral striatum. Ondansetron by itself was similar to naltrexone and the combination in the overall analysis but intermediate in a region-specific analysis. Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue-induced activation of the ventral striatum, consistent with their putative treatment efficacy.

A multi‐faceted intervention to reduce alcohol misuse and harm amongst sports people in Ireland: A controlled trial

PubMed Central

O'Farrell, Anne; Kenny, Susan; Eldin, Nazih; Wiggers, John; Wolfenden, Luke; Allwright, Shane

2017-01-01

Abstract Introduction and Aims Alcohol misuse and harm are more prevalent amongst sports people than non‐sports people. Few studies have trialled interventions to address alcohol misuse for this group. The study aimed to test the effectiveness of an intervention to reduce alcohol misuse and related harms amongst amateur sports people in Ireland. Design and Methods A controlled trial was conducted in two counties in Ireland. A random selection of sports clubs in one county received a 4 month multi‐faceted intervention. All sports clubs in a non‐adjacent county acted as control sites. Consumption of more than 21 units of alcohol per week and six or more standard drinks on a single occasion at least once per week was the primary study outcome. Alcohol Use Disorders Identification Test scores and number of alcohol‐related harms were also reported. Outcomes were assessed for cross‐sectional samples of players at pre‐intervention and post‐intervention and paired samples of players who completed surveys at both times. Generalised linear mixed model analysis was used. Results There was no evidence of effect for the primary outcomes or Alcohol Use Disorders Identification Test scores. There was a statistically significant difference in the median number of alcohol‐related harms reported by intervention group players compared with control group players at post‐intervention for the paired samples [intervention: 0; control: 3; incident rate ratio 0.56 (0.37, 0.84); P = 0.005]. Discussion and Conclusions Intervention in community sports clubs may be effective in reducing the number of alcohol‐related harms. Low levels of intervention participation and inadequate intervention dose are possible reasons for lack of a broader intervention effect. [O'Farrell A, Kingsland M, Kenny S, Eldin N, Wiggers J, Wolfenden L, Allwright S. A multi‐faceted intervention to reduce alcohol misuse and harm amongst sports people in Ireland: A controlled trial. Drug Alcohol Rev 2018;37:14–22] PMID:28782136

Intoxicated aggression: Do alcohol and stimulants cause dose-related aggression? A review.

PubMed

Kuypers, Kpc; Verkes, R J; van den Brink, W; van Amsterdam, Jgc; Ramaekers, J G

2018-06-22

Violence and drug use are significant public health challenges that are strongly linked. It is known that alcohol plays a major role in the causation of unnatural deaths and that stimulants like cocaine and amphetamine are often implicated in aggressive acts or violence. However, a clear causal relationship between these substances and aggression, and more specifically a blood concentration threshold at which intoxicated aggression emerges is lacking. In case of a crime and subsequent law enforcement, knowledge about dose-response relationships could be of pivotal importance when evaluating the role of alcohol and drugs in aggressive offences. The present review aimed to determine whether there is a causal relation between intoxication with these psychoactive substances and aggression, and to define blood concentration thresholds above which these substances elicit aggression. Empirical articles published between 2013 and 2017 and review papers containing the predefined search strings were identified through searches in the PubMed and Embase databases and additional reference list searches. The complete search query yielded 1578 publications. Initially all articles were manually screened by title and abstract. Articles with irrelevant titles, given the selected search terms and review aims were discarded. Remaining articles were carefully studied and those that did not comply with the main objectives of this review were discarded. At the end of this process, 167 titles were found eligible for review. While placebo-controlled experimental studies clearly showed a causal link between alcohol and aggression, it is evident that such a link has not yet been established for cocaine and amphetamines. In case of alcohol, it is clear that there are various individual and contextual factors that may contribute to the occurrence of an aggressive act during intoxication. A clear threshold blood alcohol concentration has not been defined yet for alcohol, but a statistically significant increase of aggression has been demonstrated at a dose of 0.75 g/kg and higher. Future studies into intoxicated aggression should include multiple doses of alcohol and stimulants and take into account individual and contextual factors. Copyright © 2018. Published by Elsevier B.V.

Acute Alcohol Consumption and Secondary Psychopathic Traits Increase Ratings of the Attractiveness and Health of Ethnic Ingroup Faces but Not Outgroup Faces

PubMed Central

Mitchell, Ian J.; Gillespie, Steven M.; Leverton, Monica; Llewellyn, Victoria; Neale, Emily; Stevenson, Isobel

2015-01-01

Studies have consistently shown that both consumption of acute amounts of alcohol and elevated antisocial psychopathic traits are associated with an impaired ability for prepotent response inhibition. This may manifest as a reduced ability to inhibit prepotent race biased responses. Here, we tested the effects of acute alcohol consumption, and elevated antisocial psychopathic traits, on judgments of the attractiveness and health of ethnic ingroup and outgroup faces. In the first study, we show that following acute alcohol consumption, at a dose that is sufficient to result in impaired performance on tests of executive function, Caucasian participants judged White faces to be more attractive and healthier compared to when sober. However, this effect did not extend to Black faces. A similar effect was found in a second study involving sober Caucasian participants where secondary psychopathic traits were related to an intergroup bias in the ratings of attractiveness for White versus Black faces. These results are discussed in terms of a model which postulates that poor prefrontal functioning leads to increases in ingroup liking as a result of impaired abilities for prepotent response inhibition. PMID:25745403

Acute alcohol consumption and secondary psychopathic traits increase ratings of the attractiveness and health of ethnic ingroup faces but not outgroup faces.

PubMed

Mitchell, Ian J; Gillespie, Steven M; Leverton, Monica; Llewellyn, Victoria; Neale, Emily; Stevenson, Isobel

2015-01-01

Studies have consistently shown that both consumption of acute amounts of alcohol and elevated antisocial psychopathic traits are associated with an impaired ability for prepotent response inhibition. This may manifest as a reduced ability to inhibit prepotent race biased responses. Here, we tested the effects of acute alcohol consumption, and elevated antisocial psychopathic traits, on judgments of the attractiveness and health of ethnic ingroup and outgroup faces. In the first study, we show that following acute alcohol consumption, at a dose that is sufficient to result in impaired performance on tests of executive function, Caucasian participants judged White faces to be more attractive and healthier compared to when sober. However, this effect did not extend to Black faces. A similar effect was found in a second study involving sober Caucasian participants where secondary psychopathic traits were related to an intergroup bias in the ratings of attractiveness for White versus Black faces. These results are discussed in terms of a model which postulates that poor prefrontal functioning leads to increases in ingroup liking as a result of impaired abilities for prepotent response inhibition.

A Methodology to Compare Insulin Dosing Recommendations in Real-Life Settings.

PubMed

Groat, Danielle; Grando, Maria A; Thompson, Bithika; Neto, Pedro; Soni, Hiral; Boyle, Mary E; Bailey, Marilyn; Cook, Curtiss B

2017-11-01

We propose a methodology to analyze complex real-life glucose data in insulin pump users. Patients with type 1 diabetes (T1D) on insulin pumps were recruited from an academic endocrinology practice. Glucose data, insulin bolus (IB) amounts, and self-reported alcohol consumption and exercise events were collected for 30 days. Rules were developed to retrospectively compare IB recommendations from the insulin pump bolus calculator (IPBC) against recommendations from a proposed decision aid (PDA) and for assessing the PDA's recommendation for exercise and alcohol. Data from 15 participants were analyzed. When considering instances where glucose was below target, the PDA recommended a smaller dose in 14%, but a larger dose in 13% and an equivalent IB in 73%. For glucose levels at target, the PDA suggested an equivalent IB in 58% compared to the subject's IPBC, but higher doses in 20% and lower in 22%. In events where postprandial glucose was higher than target, the PDA suggested higher doses in 25%, lower doses in 13%, and equivalent doses in 62%. In 64% of all alcohol events the PDA would have provided appropriate advice. In 75% of exercise events, the PDA appropriately advised an IB, a carbohydrate snack, or neither. This study provides a methodology to systematically analyze real-life data generated by insulin pumps and allowed a preliminary analysis of the performance of the PDA for insulin dosing. Further testing of the methodological approach in a broader diabetes population and prospective testing of the PDA are needed.

Effects of binge drinking on infant growth and development in an Inuit sample.

PubMed

Fraser, Sarah L; Muckle, Gina; Abdous, Belkacem B; Jacobson, Joseph L; Jacobson, Sandra W

2012-05-01

Prenatal exposure to an average of 0.5 oz absolute alcohol per day (the equivalent of 7 standard drinks per week) during pregnancy has been found to be associated with numerous adverse effects on pre- and postnatal development. In the animal model, concentrated alcohol exposure has been found to lead to more adverse effects than exposure to the same total quantity of alcohol ingested in smaller doses over a longer period of time. The primary aim of this study is to determine whether, in a population where binge drinking is common but total alcohol consumption across pregnancy is low, prenatal exposure to alcohol is associated with effects on prenatal growth, visual acuity and cognitive development during infancy. The second aim is to determine which of several indicators of alcohol consumption best predicts pre- and postnatal outcomes. Data were collected from 216 Inuit women and their infants living in Nunavik, the northern region of Québec. Maternal interviews were conducted during mid-pregnancy and at 1 and 6 months postpartum. Birth weight, length, and head circumference were assessed at delivery. Visual acuity and cognitive development were assessed at 6 months of age. In this population in which infrequent heavy episodic drinking is common, even occasional binge exposure was associated with reduced prenatal growth and poorer visual acuity at 6 months of age. A simple dichotomous measure of binge drinking during pregnancy provided the best predictor of fetal growth and 6-month acuity. The population studied here is unusual in terms of its pattern of binge alcohol consumption. To our knowledge, this is the first study to observe effects of binge drinking during pregnancy on infant growth and development in a sample where the average daily alcohol intake is low (<0.5 ounces). Copyright © 2012 Elsevier Inc. All rights reserved.

Impact of alternative technique to ageing using oak chips in alcoholic or in malolactic fermentation on volatile and sensory composition of red wines.

PubMed

Gómez García-Carpintero, E; Gómez Gallego, M A; Sánchez-Palomo, E; González Viñas, M A

2012-09-15

This paper reports on a complete study of the effect of wood, in the form of oak chips, on the volatile composition and sensory characteristics of Moravia Agria wines added at different stages of the fermentation process. Aroma compounds were analyzed by gas chromatography-mass spectrometry (GC-MS). Sensory profile was evaluated by experienced wine-testers. Oak chips were added to wines in two dose rates at different stages of the winemaking process: during alcoholic fermentation (AF), during malolactic fermentation (MLF) and in young, red Moravia Agria wine. Wines fermented with oak chips during AF showed higher concentrations of the ethyl esters of straight-chain fatty acids, ethyl, hexyl, isoamyl acetates and superior alcohols than the control wines. The higher concentrations of benzene compound, oak lactones and furanic compounds were found in wines in contact with oak chips during MLF. The use of oak chips gives rise to a different sensorial profile of wines depending of the point of addition. Higher intensities of woody, coconut, vanilla and sweet spices descriptors were obtained when a large dose rate of chips was employed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effect of Hydro-alcoholic Extract of Persian Oak (Quercus brantii) in Experimentally Gastric Ulcer

PubMed Central

Azizi, Shahrzad; Ghasemi Pirbalouti, Abdollah; Amirmohammadi, Mahdi

2014-01-01

Persian oak (Quercus brantii Lindl.) belongs the family Fagaceae, is a medicinal plant which seed flour is used to treat inflammatory and gastric ulcers by the tribes in south western Iran. The current study was done to evaluate the effect of hydro-alcoholic extract of Q. brantii seed flour for treatment of gastric ulcers induced by ethanol in Wistar rats. The hydro-alcoholic extract of Q. brantii was tested orally at doses of 250, 500, and 1000 mg/Kg, control group and standard drug (omperazole) on experimentally gastric ulceration. At the 3, 6, 9, and 14th days, ulcer index in mm2 and histopathological findings were evaluated. Results indicated the size of ulcers significantly reduced at 9, and 14 days after of Q. brantii extract treatment. Curative effect in the hydro-alcoholic induced gastric damage was 100% at 1000 mg/Kg and omeprazole, 99.8 % at 500 mg/Kg, and 95.4% at 250 mg/Kg after 14 days. Results of histopathological investigation showed the thickness of ulcerated mucosa was similar to the normal mucosa with 1000 mg/Kg of Q. brantii hydro-alcoholic extract after 14 days but in the groups treated by 250, and 500 mg/Kg, superficial erosions were visible in the central portion of the healed ulcers. In conclusion, the hydro-alcoholic extract of Q. brantii had active components (tannin = 8.2%) that accelerates ulcer healing and thus supported its traditional use. PMID:25276198

Effect of Hydro-alcoholic Extract of Persian Oak (Quercus brantii) in Experimentally Gastric Ulcer.

PubMed

Azizi, Shahrzad; Ghasemi Pirbalouti, Abdollah; Amirmohammadi, Mahdi

2014-01-01

Persian oak (Quercus brantii Lindl.) belongs the family Fagaceae, is a medicinal plant which seed flour is used to treat inflammatory and gastric ulcers by the tribes in south western Iran. The current study was done to evaluate the effect of hydro-alcoholic extract of Q. brantii seed flour for treatment of gastric ulcers induced by ethanol in Wistar rats. The hydro-alcoholic extract of Q. brantii was tested orally at doses of 250, 500, and 1000 mg/Kg, control group and standard drug (omperazole) on experimentally gastric ulceration. At the 3, 6, 9, and 14(th) days, ulcer index in mm(2) and histopathological findings were evaluated. Results indicated the size of ulcers significantly reduced at 9, and 14 days after of Q. brantii extract treatment. Curative effect in the hydro-alcoholic induced gastric damage was 100% at 1000 mg/Kg and omeprazole, 99.8 % at 500 mg/Kg, and 95.4% at 250 mg/Kg after 14 days. Results of histopathological investigation showed the thickness of ulcerated mucosa was similar to the normal mucosa with 1000 mg/Kg of Q. brantii hydro-alcoholic extract after 14 days but in the groups treated by 250, and 500 mg/Kg, superficial erosions were visible in the central portion of the healed ulcers. In conclusion, the hydro-alcoholic extract of Q. brantii had active components (tannin = 8.2%) that accelerates ulcer healing and thus supported its traditional use.

Efficacy of Continuous Dosing of Tadalafil Once Daily vs Tadalafil On Demand in Clinical Subgroups of Men With Erectile Dysfunction: A Descriptive Comparison Using the Integrated Tadalafil Databases.

PubMed

Brock, Gerald; Ni, Xiao; Oelke, Matthias; Mulhall, John; Rosenberg, Matt; Seftel, Allen; D'Souza, Deborah; Barry, Jane

2016-05-01

Various factors play a role in the development of erectile dysfunction (ED). To provide a descriptive comparison of erectile function response for tadalafil on-demand (PRN) and once-daily (OAD) dosing regimens in patients with common comorbid conditions, treatments, or risk factors that can be considered when treating ED. In total, 17 PRN and 4 OAD placebo-controlled studies were included in the integrated database in these pooled analyses. Data were analyzed from patients treated with placebo, tadalafil 10 mg (low dose), and 20 mg (high dose) for the PRN studies and placebo, tadalafil 2.5 mg (low dose), and 5 mg (high dose) for the OAD studies. The effects of tadalafil were measured using the International Index of Erectile Function administered from baseline to week 12. A descriptive comparison of the efficacy of tadalafil PRN vs OAD was examined in the clinical populations. Baseline characteristics of 4,354 men were comparable between the PRN and OAD groups, with differences seen only in the variables of race, body mass index (BMI) of at least 30 kg/m(2), and alcohol use. Tadalafil was efficacious at improving erectile function for all clinical populations, except for the low-dose OAD group, which demonstrated a weaker effect vs placebo than the high-dose OAD group, and the low- and high-dose PRN groups vs placebo for patients with BMI of at least 30 kg/m(2) for patients without a cardiovascular disorder, smokers, patients with ED duration shorter than 1 year, and patients without previous phosphodiesterase type 5 inhibitor use. Tadalafil was efficacious for patients with or without diabetes mellitus, arterial hypertension, hyperlipidemia, and alcohol use at baseline. Tadalafil OAD and PRN regimens showed efficacy in patients with ED. No clinical populations of patients with ED seemed to benefit overwhelmingly from one dose regimen over the other. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The genetics of behavioral alcohol responses in Drosophila.

PubMed

Rodan, Aylin R; Rothenfluh, Adrian

2010-01-01

Drosophila melanogaster is commonly found near rotting or fermenting fruit, reflected in its name pomace, or vinegar fly. In such environments, flies often encounter significant levels of ethanol. Three observations have made Drosophila a very promising model organism to understand the genetic contributions to the behavioral responses to alcohol. First, similar to higher vertebrates, flies show hyperactivation upon exposure to a low to medium dose of alcohol, while high doses can lead to sedation. In addition, when given a choice, flies will actually prefer alcohol-containing food over regular food. Second, the genes and biochemical pathways implicated in controlling these behavioral responses in flies are also participating in determining alcohol responses, and drinking behavior in mammals. Third, the fact that flies have been studied genetically for over one hundred years means that an exceptional repertoire of genetic tools are at our disposal. Here, we will review some of these tools and experimental approaches, survey the methods for, and measures after Drosophila ethanol exposure, and discuss the different molecular components and functional pathways involved in these behavioral responses to alcohol. Copyright 2010 Elsevier Inc. All rights reserved.

High doses of alcohol during pregnancy cause DNA damages in osteoblasts of newborns rats.

PubMed

Carvalho, Isabel Chaves Silva; Dutra, Tamires Pereira; Andrade, Dennia Perez De; Balducci, Ivan; Pacheco-Soares, Cristina; Rocha, Rosilene Fernandes da

2016-02-01

Alcohol exerts teratogenic effects and its consumption during pregnancy can cause deficit of bone development. The aim of the current study was to evaluate the genotoxic effects of prenatal exposure to ethanol on newborn rat osteoblasts. Wistar rats were initially divided into two groups: Ethanol group which received Ethanol 20% V/V in liquid diet and solid diet ad libitum, and Control group, which received solid diet and water ad libitum. Each group received a specific diet for 8 weeks before breeding and throughout three weeks of gestation and the treatment was finished on the day the pups were killed. On the fifth day of life, the pups from each group were killed for removal of the calvaria and isolation of osteogenic cells by sequential enzymatic digestion. The cells were cultured for a maximum period of 14 days. The detection of genotoxic effects of alcohol was investigated by the comet and the micronucleus assay. Micronucleus and comet assay showed significant increases in DNA damage at 7 days in Ethanol group (p = 0.0302, p = 0.0446, respectively). However, at 14 days both assay showed no significant difference between the groups (p = 0.6194, p = 0.8326, respectively). Our results showed that prenatal exposure to ethanol induced DNA damage in osteoblasts, as shown by micronucleus formation and higher percentage of DNA in the comet tail. It can be concluded that prenatal exposure to ethanol damages osteoblast DNA in newborns exposed to high doses of ethanol during pregnancy, suggesting that prenatal ethanol consumption has a direct effect on fetal osteoblasts. © 2015 Wiley Periodicals, Inc.

[Effect of alcohol intake on the ability to pilot aircraft].

PubMed

Ushakov, I B; Egorov, S V

1996-01-01

During the initial 4 hours after alcohol intake at a dose of 1.9 g/kg aircraft operators displayed disturbances in the psychic processes and functions responsible for each (from information reception and processing up to decision-making and building-up the controlling actions) structural elements in their activity resulting in considerable limitation or a complete failure to pilot aircraft. Main disorders included inability to correctly analyse flight situation and loss of skills to automatically control simulator, a sudden depletion of psychophysiological reserves and deterioration of operator's reliability. Less elaborated professional skills appear to be the most vulnerable.

Low-dose ethanol aggravates allergic dermatitis in mice.

PubMed

Sakazaki, Fumitoshi; Ogino, Hirofumi; Arakawa, Tomohiro; Okuno, Tomofumi; Ueno, Hitoshi

2014-08-01

Alcohol injures dendritic cells and suppresses cellular immunity, while some evidence indicates that drinking alcohol aggravates allergic asthma. This study investigated the effect of low doses of ethanol in enhancing allergic reactions in the skin of mice. Liquid food containing alcohol was administered to conventional NC/Nga mice to induce alcoholic hepatic steatosis, and spontaneous dermatitis was evaluated. BALB/c mice were administered approximately 1 g/kg body weight of ethanol by gavage, and contact hypersensitivity (CHS) or active cutaneous anaphylaxis (ACA) was induced. Spleens were collected 24 h after the elicitation of CHS and mRNA expressions of interferon (IFN)-γ, interleukin (IL)-4, IL-6, IL-10, and IL-18 were measured by quantitative RT-PCR. Alcohol-containing diet exaggerated spontaneous dermatitis in conventional NC/Nga mice and contact hypersensitivity in BALB/c mice. Ethanol administered by gavage for 5 days enhanced contact hypersensitivity in BALB/c mice. Ethanol administration with gavage also enhanced ACA of BALB/c mice. Ethanol did not affect mRNA expression of IFN-γ and IL-4, but did enhance IL-6, IL-10, and IL-18 mRNA expression. Histological evaluation revealed an absence of hepatic steatosis in mice administered ethanol by gavage for 5 days. In ethanol-administered mice, inflamed areas presented as lesions or a local extreme accumulation of mononuclear cells in the epidermis. These findings suggest that ethanol enhances the expression of inflammatory cytokines independently from T helper (Th)1/Th2 cytokine phenotypes, causing abnormalities in the epidermis resulting in exacerbated allergic reactivity. Copyright © 2014 Elsevier Inc. All rights reserved.

Nicotine as a Factor in Stress Responsiveness Among Detoxified Alcoholics

PubMed Central

Gilbertson, Rebecca; Frye, Reginald F.; Nixon, Sara Jo

2011-01-01

Aims: The effect of transdermal nicotine on stress reactivity was investigated in currently smoking, detoxified, substance-dependent individuals (65% alcohol dependent, n = 51; 31 male) following a psychosocial stressor. Methods: Using a randomized, double-blind, placebo-controlled design, subjects were assigned to receive either active transdermal nicotine (low or high dose) or placebo. Six hours following nicotine administration, subjects performed a laboratory psychosocial stressor consisting of two 4-min public-speaking sessions. Results: Consistent with prior reports, substance-dependent individuals displayed a blunted stress response. However, a review of the cortisol distribution data encouraged additional analyses. Notably, a significant minority of the substance-dependent individuals (33%) demonstrated elevated poststress cortisol levels. This group of responders was more likely to be alcohol dependent and to have received the high dose of nicotine [χ2(2) = 32, P < 0.0001], [χ2(2) = 18.66, P < 0.0001]. Differences in salivary cortisol responses between responders and nonresponders could not be accounted for by the length of sobriety, nicotine withdrawal levels, anxiety or depressive symptomatology at the time of the psychosocial stressor. Conclusion: These results suggest that nicotine administration may support a normalization of the salivary cortisol response following psychosocial stress in subgroups of substance-dependent individuals, particularly those who are alcohol dependent. Given the association between blunted cortisol levels and relapse, and the complex actions of nicotine at central and peripheral sites, these findings support the systematic study of factors including nicotine, which may influence stress reactivity and the recovery process in alcohol-dependent individuals. PMID:21045074

Study protocol: Asking QUestions about Alcohol in pregnancy (AQUA): a longitudinal cohort study of fetal effects of low to moderate alcohol exposure.

PubMed

Muggli, Evelyne; O'Leary, Colleen; Forster, Della; Anderson, Peter; Lewis, Sharon; Nagle, Cate; Craig, Jeffrey M; Donath, Susan; Elliott, Elizabeth; Halliday, Jane

2014-09-03

Despite extensive research, a direct correlation between low to moderate prenatal alcohol exposure (PAE) and Fetal Alcohol Spectrum Disorders has been elusive. Conflicting results are attributed to a lack of accurate and detailed data on PAE and incomplete information on contributing factors. The public health effectiveness of policies recommending complete abstinence from alcohol during pregnancy is challenged by the high frequency of unplanned pregnancies, where many women consumed some alcohol prior to pregnancy recognition. There is a need for research evidence emphasizing timing and dosage of PAE and its effects on child development. Asking QUestions about Alcohol (AQUA) is a longitudinal cohort aiming to clarify the complex effects of low to moderate PAE using specifically developed and tested questions incorporating dose, pattern and timing of exposure. From 2011, 2146 pregnant women completed a questionnaire at 8-18 weeks of pregnancy. Further prenatal data collection took place via a questionnaire at 26-28 weeks and 35 weeks gestation. Extensive information was obtained on a large number of risk factors to assist in understanding the heterogeneous nature of PAE effects. 1571 women (73%) completed all three pregnancy questionnaires. A biobank of DNA from maternal and infant buccal cells, placental biopsies and cord blood mononuclear cells will be used to examine epigenetic state at birth as well as genetic factors in the mother and child. Participants will be followed up at 12 and 24 months after birth to assess child health and measure infant behavioural and sensory difficulties, as well as family environment and parenting styles. A subgroup of the cohort will have 3D facial photography of their child at 12 months and a comprehensive developmental assessment (Bayley Scales of Infant & Toddler Development, Bayley-III) at two years of age. Using detailed, prospective methods of data collection, the AQUA study will comprehensively examine the effects of low to moderate alcohol consumption throughout pregnancy on child health and development, including the role of key mediators and confounders. These data will ultimately contribute to policy review and development, health professional education and information about alcohol consumption for pregnant women in the future.

Alcohol dose dumping: The influence of ethanol on hot-melt extruded pellets comprising solid lipids.

PubMed

Jedinger, N; Schrank, S; Mohr, S; Feichtinger, A; Khinast, J; Roblegg, E

2015-05-01

The objective of the present study was to investigate interactions between alcohol and hot-melt extruded pellets and the resulting drug release behavior. The pellets were composed of vegetable calcium stearate as matrix carrier and paracetamol or codeine phosphate as model drugs. Two solid lipids (Compritol® and Precirol®) were incorporated into the matrix to form robust/compact pellets. The drug release characteristics were a strong function of the API solubility, the addition of solid lipids, the dissolution media composition (i.e., alcohol concentration) and correspondingly, the pellet wettability. Pellets comprising paracetamol, which is highly soluble in ethanol, showed alcohol dose dumping regardless of the matrix composition. The wettability increased with increasing ethanol concentrations due to higher paracetamol solubilities yielding increased dissolution rates. For pellets containing codeine phosphate, which has a lower solubility in ethanol than in acidic media, the wettability was a function of the matrix composition. Dose dumping occurred for formulations comprising solid lipids as they showed increased wettabilities with increasing ethanol concentrations. In contrast, pellets comprising calcium stearate as single matrix component showed robustness in alcoholic media due to wettabilities that were not affected by the addition of ethanol. The results clearly indicate that the physico-chemical properties of the drug and the matrix systems are crucial for the design of ethanol-resistant dosage forms. Moreover, hydrophobic calcium stearate can be considered a suitable matrix system that minimizes the risk of ethanol-induced dose dumping for certain API's. Copyright © 2015 Elsevier B.V. All rights reserved.

Tobacco, alcohol use, and risks of laryngeal and lung cancer by subsite and histologic type in Turkey.

PubMed

Dosemeci, M; Gokmen, I; Unsal, M; Hayes, R B; Blair, A

1997-09-01

Effects of tobacco smoking and alcohol use on risks of cancers of the larynx and lung have been evaluated extensively in industrialized countries. Few studies on the effect of these risk factors have been reported from developing countries. We conducted a case-control study to evaluate risks of laryngeal and lung cancers in men by subsite and cell type in relation to smoking and alcohol drinking in Turkey, a country where smoking and alcohol consumption patterns are different from those in industrialized countries. We identified 832 laryngeal and 1,210 lung cancer cases and 829 controls with information on smoking and alcohol use (amount and duration) and histologic cell type from an oncology treatment center of a Social Security Agency hospital in Istanbul, Turkey, admitted between 1979 and 1984. Both laryngeal and lung cancer showed significant associations with smoking and alcohol drinking, but no monotonic dose-response was obtained for alcohol drinking. Among smokers, the highest risks were observed in the supraglottis region of the larynx (odds ratio [OR] = 4.1) after adjustment for age and alcohol use. Among alcohol drinkers, the highest risks were observed in the glottis region of the larynx (OR = 1.7) after adjustment for age and smoking. In the analysis by the cell type of lung cancer among ever-smokers, small cell type showed the highest risk (OR = 5.4), while it showed no association with alcohol drinking. Cumulative cigarette use (pack-years) and number of cigarettes per day showed stronger associations than years smoked for both cancer sites. The relative risks of joint exposure to smoking and alcohol were 12.2 for laryngeal cancer and 14.1 for lung cancer among heavy smokers and heavy alcohol drinkers. This study provides epidemiologic evidence from Turkey that smoking and alcohol use are associated with risks of cancers of the larynx and lung.

Orexin-1 receptor blockade suppresses compulsive-like alcohol drinking in mice

PubMed Central

Lei, Kelly; Wegner, Scott A.; Yu, Ji-Hwan; Hopf, F. Woodward

2016-01-01

Addiction is promoted by pathological motivation for addictive substances, and, despite extensive efforts, alcohol use disorders (AUDs) continue to extract a very high social, physical, and economic toll. Compulsive drinking of alcohol, where consumption persists even when alcohol is paired with negative consequences, is considered a particular obstacle for treating AUDs. Aversion-resistant alcohol intake in rodents, e.g. where rodents drink even when alcohol is paired with the bitter tastant quinine, has been considered to model some compulsive aspects of human alcohol consumption. However, the critical mechanisms that drive compulsive-like drinking are only beginning to be identified. The neuropeptide orexin has been linked to high motivation for cocaine, preferred foods, and alcohol. Thus, we investigated the role of orexin receptors in compulsive-like alcohol drinking, where C57BL/6 mice had 2-hr daily access to 15% alcohol with or without quinine (100 µM). We found that systemic administration of the widely used selective orexin-1 receptor (OX1R) blocker, SB-334867 (SB), significantly reduced compulsive-like consumption at doses lower than those reported to reduce quinine-free alcohol intake. The dose of 3-mg/kg SB, in particular, suppressed only compulsive-like drinking. Furthermore, SB did not reduce concurrent water intake during the alcohol drinking sessions, and did not alter saccharin+quinine consumption. In addition, the OX2R antagonist TCS-OX2-29 (3 or 10 mg/kg) did not alter intake of alcohol with or without quinine. Together, our results suggest that OX1R signaling is particularly important for promoting compulsive-like alcohol drinking, and that OX1Rs might represent a novel therapy to counteract compulsive aspects of human AUDs. PMID:27523303

Reversal of alcohol-induced effects on response control due to changes in proprioceptive information processing.

PubMed

Stock, Ann-Kathrin; Mückschel, Moritz; Beste, Christian

2017-01-01

Recent research has drawn interest to the effects of binge drinking on response selection. However, choosing an appropriate response is a complex endeavor that usually requires us to process and integrate several streams of information. One of them is proprioceptive information about the position of limbs. As to now, it has however remained elusive how binge drinking affects the processing of proprioceptive information during response selection and control in healthy individuals. We investigated this question using neurophysiological (EEG) techniques in a response selection task, where we manipulated proprioceptive information. The results show a reversal of alcohol-induced effects on response control due to changes in proprioceptive information processing. The most likely explanation for this finding is that proprioceptive information does not seem to be properly integrated in response selection processes during acute alcohol intoxication as found in binge drinking. The neurophysiological data suggest that processes related to the preparation and execution of the motor response, but not upstream processes related to conflict monitoring and spatial attentional orienting, underlie these binge drinking-dependent modulations. Taken together, the results show that even high doses of alcohol have very specific effects within the cascade of neurophysiological processes underlying response control and the integration of proprioceptive information during this process. © 2015 Society for the Study of Addiction.

Effect of bromocriptine on acute ethanol tolerance in UChB rats.

PubMed

Tampier, L; Prado, C; Quintanilla, M E; Mardones, J

1999-07-01

It has been suggested that a higher capacity to develop acute tolerance during a single dose of ethanol may promote higher ethanol consumption in alcohol-preferring rodents. Several studies have shown that the dopaminergic system may be involved in voluntary ethanol consumption. In the present paper we studied the effect of bromocriptine, a dopaminergic agonist drug, that is known to reduce voluntary consumption of ethanol, on acute tolerance in high (UChB) ethanol consumer rats. Acute tolerance was evaluated in bromocriptine and saline-treated rats by motor impairment induced by a subnarcotic dose of ethanol of 2.3 g/kg IP using a modified tilting plane test. Results showed a highly significant positive correlation between acute tolerance and the voluntary ethanol consumption by the rat. Bromocriptine treatment decreased ethanol consumption and also decreased acute tolerance development. This adds further support to the postulate that the acquisition of acute tolerance to ethanol may promote increased alcohol consumption. Moreover, these results also suggest that dopaminergic receptors involved in ethanol voluntary consumption may also be in acute tolerance development.

Unravelling motor behaviour hallmarks in intoxicated adolescents: methylmercury subtoxic-dose exposure and binge ethanol intake paradigm in rats.

PubMed

Oliveira, Aline Nascimento; Pinheiro, Alana Miranda; Belém-Filho, Ivaldo Jesus Almeida; Fernandes, Luanna Melo Pereira; Cartágenes, Sabrina Carvalho; Ribera, Paula Cardoso; Fontes-Júnior, Enéas Andrade; Crespo-Lopez, Maria Elena; Monteiro, Marta Chagas; Lima, Marcelo Oliveira; Maia, Cristiane Socorro Ferraz

2018-05-24

Methylmercury (MeHg) is a hazardous environmental pollutant, affecting Amazon basin communities by anthropogenic activities. The exact safe level of MeHg exposure is unclear, despite the efforts of health international societies to avoid mercury (Hg) poisoning. Central nervous system is severely impacted by Hg intoxication, reflecting on motor impairment. In addition, alcohol has been associated to an overall brain damage. According to lifestyle of Amazon riverside communities, alcohol intake occurs frequently. Thus, we investigated if continuous MeHg exposure at low doses during adolescence displays motor deficits (experiment 1). In the experiment 2, we examine if the co-intoxication (i.e. MeHg plus ethanol exposure) during adolescence intensify motor damage. In the experiment 1, Wistar adolescent rats (31 days old) received chronic exposure to low dose (CELD) of MeHg (40 μg/kg/day) for 35 days. For the experiment 2, five sessions of alcohol binge drinking paradigm (3ON-4OFF; 3.0 g/kg/day) were employed associated to MeHg intoxication. Motor behaviour was evaluated by the open field, pole test, beam walking and rotarod paradigms. CELDS of MeHg display motor function damage, related to hypoactivity, bradykinesia-like behaviour, coordination deficits and motor learning impairment. Co-intoxication of MeHg plus ethanol reduced cerebellar Hg content, however also resulted in motor behavioural impairment, as well as additive effects on bradykinesia and fine motor evaluation.

Alcohol use in motion pictures and its relation with early-onset teen drinking.

PubMed

Sargent, James D; Wills, Thomas A; Stoolmiller, Mike; Gibson, Jennifer; Gibbons, Frederick X

2006-01-01

Little is known about the impact of viewing depictions of alcohol in entertainment media on adolescent drinking behavior. Our aims were to assess drinking in a sample of popular contemporary movies and to examine the association of movie alcohol exposure with early-onset drinking in an adolescent sample. We conducted a school-based cross-sectional survey (N=4655) with longitudinal follow-up of never-drinkers (N=2406) involving adolescents ages 10-14 years and recruited from 15 New Hampshire and Vermont schools. Screen depictions of alcohol use were timed for each of 601 popular contemporary movies. Each adolescent was asked if he/she had seen a unique list of 50 movie titles, randomly selected from the larger pool. Movie alcohol use was summed for movies the adolescent had seen, adjusted to reflect exposure to the larger pool and modeled as a continuous variable. Ninety-two percent of the movies in the sample depicted drinking; median screen time for movie alcohol use was 2.5 minutes (interquartile range [IQR]: 0.9-5.0 minutes). Median exposure to movie alcohol use from the 601 movies was 8.6 hours (IQR: 4.6-13.5 hours). Overall 23.1% of the cross-sectional sample had tried alcohol, and 14.8% of initial nondrinkers had tried alcohol at the follow-up assessment. We found statistical evidence to support a curvilinear association between higher exposure to movie alcohol use and increased risk of prevalent and incident alcohol use, with a statistically significant linear and quadratic effect, and suggesting a higher dose-effect relationship at lower movie alcohol exposure levels compared to higher levels. The linear and the quadratic associations remained strong and significant in cross-sectional and prospective models after controlling for sociodemographics (grade in school, school, gender, parent education), personality characteristics of the adolescent (sensation seeking, rebelliousness, self-esteem), school performance, parenting style, and smoking experimentation, suggesting that exposure to movie alcohol use is an independent risk factor for early-onset alcohol use. This study provides the first evidence for an association between exposure to movie alcohol use and early-onset teen drinking. The association is moderate in effect size and independent of a number of potential confounders. Because exposure to movie alcohol use is common, it may have important population implications as a potentially modifiable risk factor.

Protective effect of Tribulus terrestris fruit extract on cerulein-induced acute pancreatitis in mice

PubMed Central

Borran, Mina; Minaiyan, Mohsen; Zolfaghari, Behzad; Mahzouni, Parvin

2017-01-01

Objective: Antioxidant, anti-inflammatory, analgesic and antimicrobial activities of Tribulus terrestris (T. terrestris) could be helpful in the treatment of acute pancreatitis; thus, this study was designed to investigate the effects of T. terrestris on cerulein-induced acute pancreatitis in mice. Materials and Methods: Three doses (100, 200 and 400 mg/kg) of T. terrestris hydro-alcoholic extract were administered both orally (60 minutes before pancreatitis induction, p.o.) and intra-peritoneally (30 minutes before pancreatitis induction, i.p.) to different groups of mice (n=6). Pancreatitis was induced by five injections (i.p.) of cerulein 50μg/kg body weight with 1 hr intervals. Animals were euthanized 5 hr after the last injection of cerulein and tissue injures were assessed biochemically and pathologically. Results: T. terrestris extract 200 and 400mg/kg (p.o.) and T. terrestris extract 400 mg/kg (i.p.) reduced pancreatic tissue myeloperoxidase (MPO) activity and serum amylase and lipase levels and alleviated histological parameters. Conclusion: These data suggest that T. terrestris hydro-alcoholic extract was effective in protecting against experimental acute pancreatitis and possibly the efficacy depends on dose and route of administration. PMID:28748172

Gamma-hydroxybutyric acid in male and female cynomolgus monkeys trained to discriminate 1.0 or 2.0 g/kg ethanol.

PubMed

Helms, Christa M; Rogers, Laura S M; Grant, Kathleen A

2008-07-01

Gamma-hydroxybutyric acid has been proposed as a pharmacotherapy for alcoholism in part based on similar discriminative stimulus effects as ethanol. To date, drug discrimination studies with gamma-hydroxybutyric acid and ethanol have exclusively used rodents or pigeons as subjects. To evaluate possible differences between species, sex, and route of administration, this study investigated the substitution of gamma-hydroxybutyric acid (intragastrically or intramuscularly) for ethanol 30 or 60 min after administration in male (n=6) and female (n=7) cynomolgus monkeys trained to discriminate 1.0 and 2.0 g/kg ethanol. At least one dose of gamma-hydroxybutyric acid completely or partially substituted for ethanol in three of the 13 monkeys tested, with each case occurring in female monkeys. Ethanol-appropriate responding did not increase with gamma-hydroxybutyric acid dose. Monkeys were more sensitive to the response rate decreasing effects of gamma-hydroxybutyric acid administered intramuscularly compared with intragastrically. The lack of gamma-hydroxybutyric acid substitution for ethanol suggests that these drugs have different receptor bases for discrimination. Furthermore, the data do not strongly support shared discriminative stimulus effects as the rationale for gamma-hydroxybutyric acid pharmacotherapy for alcoholism.

Effects of obeticholic acid on lipoprotein metabolism in healthy volunteers.

PubMed

Pencek, R; Marmon, T; Roth, J D; Liberman, A; Hooshmand-Rad, R; Young, M A

2016-09-01

The bile acid analogue obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist in development for treatment of several chronic liver diseases. FXR activation regulates lipoprotein homeostasis. The effects of OCA on cholesterol and lipoprotein metabolism in healthy individuals were assessed. Two phase I studies were conducted to evaluate the effects of repeated oral doses of 5, 10 or 25 mg OCA on lipid variables after 14 or 20 days of consecutive administration in 68 healthy adults. Changes in HDL and LDL cholesterol levels were examined, in addition to nuclear magnetic resonance analysis of particle sizes and sub-fraction concentrations. OCA elicited changes in circulating cholesterol and particle size of LDL and HDL. OCA decreased HDL cholesterol and increased LDL cholesterol, independently of dose. HDL particle concentrations declined as a result of a reduction in medium and small HDL. Total LDL particle concentrations increased because of an increase in large LDL particles. Changes in lipoprotein metabolism attributable to OCA in healthy individuals were found to be consistent with previously reported changes in patients receiving OCA with non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. © 2016 John Wiley & Sons Ltd.

Effect of Withinia Somnifera and Shilajit on Alcohol Addiction in Mice.

PubMed

Bansal, Priya; Banerjee, Sugato

2016-05-01

Alcohol addiction is a social problem leading to both loss of health and economic prosperity among addicted individuals. Common properties of anti-addictive compounds include anti-anxiety, anticonvulsants, anti-depressant, and nootropic actions primarily through modulation of gamma-aminobutyric acid (GABA) and serotonergic systems. Here, we screen ashwagandha and shilajit known ethnopharmacologically as nervine tonic and adaptogenic herbs for possible anti-addictive potential. Effect of ashwagandha churna and shilajit was measured on ethanol withdrawal anxiety using elevated plus maze. Role of ashwagandha and shilajit on chronic ethanol consumption (21 days) was measured using two bottle choice protocol of voluntary drinking. We also measured the effect of the above herbs on corticohippocampal GABA, dopamine, and serotonin levels. Both ashwagandha and shilajit were found to reduce alcohol withdrawal anxiety in a dose-dependent manner. These herbs alone or in combination also decreased ethanol intake and increased water intake significantly after 21 days of chronic administration. Chronic administration of ashwagandha was found to significantly increase GABA and serotonin levels whereas shilajit altered cortico-hippocampal dopamine in mice. These central nervous system active herbs alone or in combination reduced both alcohol dependence and withdrawal thus showing promising anti-addictive potential. Withinia Somnifera alone and in combination with Shilajeet prevented ethanol withdrawal and alcohol addiction Abbreviations used: GABA: Gama aminobutyric acid, CNS: Central Nervous System, CPP:Condition place preference, DA: Dopamine, 5-HT: 5-hydroxytryptamine, NMDA:N-methyl-D-aspartate.

Alcohol consumption and lung cancer risk in never smokers.

PubMed

García-Lavandeira, José Antonio; Ruano-Ravina, Alberto; Barros-Dios, Juan Miguel

2016-01-01

The main objective of this study is to analyse the role of alcohol consumption on lung cancer risk in people who have never smoked. We conducted a systematic review of the scientific literature following the PRISMA statement. We searched Medline, EMBASE and CINAHL using different combinations of MeSH terms and free text. We included cohort studies, pooled cohort studies and case-control studies comprising at least 25 anatomopathologically-confirmed diagnoses of lung cancer cases, a sample size larger than 100 individuals and more than five years of follow-up for cohort studies. We excluded studies that did not specifically report results for never smokers. We developed a quality score to assess the quality of the included papers and we ultimately included 14 investigations with a heterogeneous design and methodology. Results for alcohol consumption and lung cancer risk in never smokers are inconclusive; however, several studies showed a dose-response pattern for total alcohol consumption and for spirits. Heterogeneous results were found for wine and beer. No clear effect is observed for alcohol consumption. Due to the limited evidence, no conclusion can be drawn for beer or wine consumption. There is little research available on the effect of alcohol on lung cancer risk for people who have never smoked, and more studies are urgently needed on this topic. Copyright © 2016 SESPAS. Published by Elsevier Espana. All rights reserved.

Extraversion and the Rewarding Effects of Alcohol in a Social Context

PubMed Central

Fairbairn, Catharine E.; Sayette, Michael A.; Wright, Aidan G. C.; Levine, John M.; Cohn, Jeffrey F.; Creswell, Kasey G.

2015-01-01

The personality trait of extraversion has been linked to problematic drinking patterns. Researchers have long hypothesized that such associations are attributable to increased alcohol-reward sensitivity among extraverted individuals, and surveys suggest that individuals high in extraversion gain greater mood enhancement from alcohol than those low in extraversion. Surprisingly, however, alcohol administration studies have not found individuals high in extraversion to experience enhanced mood following alcohol consumption. Of note, prior studies have examined extraverted participants—individuals who self-identify as being highly social—consuming alcohol in isolation. In the present research, we used a group drinking paradigm to examine whether individuals high in extraversion gained greater reward from alcohol than did those low in extraversion and, further, whether a particular social mechanism (partners’ Duchenne smiling) might underlie alcohol reward sensitivity among extraverted individuals. Social drinkers (n = 720) consumed a moderate dose of alcohol, placebo, or control beverage in groups of three over the course of 36-min. This social interaction was video-recorded, and Duchenne smiling was coded using the Facial Action Coding System. Results indicated that participants high in extraversion reported significantly more mood enhancement from alcohol than did those low in extraversion. Further, mediated moderation analyses focusing on Duchenne smiling of group members indicated that social processes fully and uniquely accounted for alcohol reward-sensitivity among individuals high in extraversion. Results provide initial experimental evidence that individuals high in extraversion experience increased mood-enhancement from alcohol and further highlight the importance of considering social processes in the etiology of Alcohol Use Disorder. PMID:25844684

Extraversion and the Rewarding Effects of Alcohol in a Social Context.

PubMed

Fairbairn, Catharine E; Sayette, Michael A; Wright, Aidan G C; Levine, John M; Cohn, Jeffrey F; Creswell, Kasey G

2015-08-01

The personality trait of extraversion has been linked to problematic drinking patterns. Researchers have long hypothesized that such associations are attributable to increased alcohol-reward sensitivity among extraverted individuals, and surveys suggest that individuals high in extraversion gain greater mood enhancement from alcohol than those low in extraversion. Surprisingly, however, alcohol administration studies have not found individuals high in extraversion to experience enhanced mood following alcohol consumption. Of note, prior studies have examined extraverted participants-individuals who self-identify as being highly social-consuming alcohol in isolation. In the present research, we used a group drinking paradigm to examine whether individuals high in extraversion gained greater reward from alcohol than did those low in extraversion and, further, whether a particular social mechanism (partners’ Duchenne smiling) might underlie alcohol reward sensitivity among extraverted individuals. Social drinkers (n 720) consumed a moderate dose of alcohol, placebo, or control beverage in groups of 3 over the course of 36 min. This social interaction was video-recorded, and Duchenne smiling was coded using the Facial Action Coding System. Results indicated that participants high in extraversion reported significantly more mood enhancement from alcohol than did those low in extraversion. Further, mediated moderation analyses focusing on Duchenne smiling of group members indicated that social processes fully and uniquely accounted for alcohol reward-sensitivity among individuals high in extraversion. Results provide initial experimental evidence that individuals high in extraversion experience increased mood-enhancement from alcohol and further highlight the importance of considering social processes in the etiology of alcohol use disorder. (c) 2015 APA, all rights reserved).

Evaluation of chronic alcohol self-administration by a 3-bottle choice paradigm in adult male rats. Effects on behavioural reactivity, spatial learning and reference memory.

PubMed

Cacace, Silvana; Plescia, Fulvio; La Barbera, Marco; Cannizzaro, Carla

2011-06-01

Chronic ethanol consumption is able to modify emotional behaviour and cognition in humans. In particular, the effects exerted by alcohol may depend on doses, time and modalities of administration. In this study we investigated, in adult male rats, ethanol self-administration and preference patterns using a 3-bottle choice paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on novelty-induced explorative behaviour in the open field, and on spatial learning and reference memory in the Morris water maze was also evaluated. Our results indicate that: (i) rats show a higher preference for alcohol, in the first two weeks of the paradigm, displaying a higher consumption of 10% ethanol solution than white wine; in the last two weeks, they reduce their alcoholic preference, drinking the same moderate amounts of the two alcoholic beverages; (ii) at the fourth week of the free-access paradigm rats show a high explorative behaviour in the central squares of the open field and an improvement in spatial information processing in the new-place learning task of the Morris water maze. In conclusion our data suggest that, interestingly, rats exposed to the free-access paradigm were able to self-regulate their alcoholic intake, and indicated that a moderate alcohol consumption was able to induce an increase in behavioural reactivity and an enhancement in spatial learning flexibility. Copyright © 2011 Elsevier B.V. All rights reserved.

Transgenerational Transmission of the Effect of Gestational Ethanol Exposure on Ethanol Use-Related Behavior

PubMed Central

Nizhnikov, Michael E.; Popoola, Daniel O.; Cameron, Nicole M.

2018-01-01

Background Prenatal alcohol exposure (PAE) enhances the risk for alcoholism by increasing the propensity to consume alcohol and altering neurophysiological response to alcohol challenge. Transgenerationally transmittable genetic alterations have been implicated in these behavioral changes. To date, transgenerational transmission of PAE-induced behavioral responses to alcohol has never been experimentally investigated. Therefore, we explored the transgenerational transmission of PAE-induced behavioral effects across 3 generations. Methods Pregnant Sprague Dawley dams received 1 g/kg ethanol (EtOH) or water daily on gestational days 17 through 20 via gavage, or remained untreated in their home cages. To produce second filial (F2) or F3 generations, similarly treated adult F1 or F2 offspring were mated and left undisturbed through gestation. On postnatal day (PND) 14, male and female F1, F2, and F3 offspring were tested for consumption of 5% (w/v) EtOH (in water), or water. Using the loss of righting reflex (LORR) paradigm on PND 42, F1 and F2 adolescent male offspring were tested for sensitivity to acute EtOH-induced sedation–hypnosis at 3.5 or 4.5 g/kg dose. F3 male adolescents were similarly tested at 3.5 g/kg dose. Blood EtOH concentration (BEC) was measured at waking. Results EtOH exposure increased EtOH consumption compared to both water and untreated control groups in all generations. EtOH-treated group F1 and F2 adolescents displayed attenuated LORR duration compared to the water group. No attenuated LORR was observed in the F3 generation. BEC at waking corroborated with the significant LORR duration differences while also revealing differences between untreated control and water groups in F1 and F2 generations. Conclusions Our results provide novel behavioral evidence attesting that late gestational moderate EtOH exposure increases EtOH intake across 3 generations and may alter sensitivity to EtOH-induced sedation–hypnosis across 2 generations. PMID:26876534

A 3-year study of addiction mutual-help group participation following intensive outpatient treatment.

PubMed

Kelly, John F; Stout, Robert; Zywiak, William; Schneider, Robert

2006-08-01

Addiction-focused mutual-help group participation is associated with better substance use disorder (SUD) treatment outcomes. However, little has been documented regarding which types of mutual-help organizations patients attend, what levels of participation may be beneficial, and which patients, in particular, are more or less likely to participate. Furthermore, much of the evidence supporting the use of these organizations comes from studies examining participation and outcomes concurrently, raising doubts about cause-effect connections, and little is known about influences that may moderate the degree of any general benefit. Alcohol-dependent outpatients (N=227; 27% female; M age=42) enrolled in a randomized-controlled telephone case monitoring trial were assessed at treatment intake and at 1, 2, and 3 years postdischarge. Lagged-panel, hierarchical linear models tested whether mutual-help group participation in the first and second year following treatment predicted subsequent outcomes and whether these effects were moderated by gender, concurrent axis I diagnosis, religious preference, and prior mutual-help experience. Robust regression curve analysis was used to examine dose-response relationships between mutual-help and outcomes. Mutual-help participation was associated with both greater abstinence and fewer drinks per drinking day and this relationship was not found to be influenced by gender, Axis I diagnosis, religious preference, or prior mutual-help participation. Mutual-help participants attended predominantly Alcoholics Anonymous and tended to be Caucasian, be more educated, have prior mutual-help experience, and have more severe alcohol involvement. Dose-response curve analyses suggested that even small amounts of participation may be helpful in increasing abstinence, whereas higher doses may be needed to reduce relapse intensity. Use of mutual-help groups following intensive outpatient SUD treatment appears to be beneficial for many different types of patients and even modest levels of participation may be helpful. Future emphasis should be placed on ways to engage individuals with these cost-effective resources over time and to gather and disseminate evidence regarding additional mutual-help organizations.

Variation in response to drugs: Part II. Environmental and nutritional variables.

PubMed

Fraser, H S; Tibbits, R C

1983-06-01

The importance of environmental factors for drug metabolism has recently been established. This paper reviews the major environmental and nutritional sources of variation in drug response. Environmental variables examined include drug interactions, alcohol, cigarette smoking, marijuana, other socially used drugs, steroid oral contraceptives (OCs), and agricultural industrial contaminants. Drug-drug interactions act chiefly by induction or inhibition of the microsomal metabolizing enzyme system. The effect of alcohol on the metabolism of other drugs depends on the drug, the dose of alcohol, the duration of exposure, and possibly diet and the presence of disease. Cigarette smoke affects the biotransformation of several drugs, and smokers often require higher doses of oxidized drugs. An additive effect of cigarette smoke and marijuana has been observed, resulting in the halving of the half-life of some drugs. Caffeine may serve as a competitive inhibitor of microsomal enzymes. Chemical pollutants such as chlorinated and polycyclic hydrocarbons can alter the hepatic drug metabolizing enzyme activity. The nutritional variables examined include malnutrition, anemia, vegetarian diets, dietary contaminants, and specific microconstituents of diet. Total dietary protein has a more critical effect on drug metabolism than fat or carbohydrate. These findings indicate that many factors in each patient are capable of altering drug response. Assessment of these variables permits more rational prescribing practices. For example, most patients over age 70 or vegetarian OC users require half the usual dosage of most drugs, whereas smokers and industrial workers require higher than recommended doses. Plasma measurements are of value in such assessments. Developing countries are advised to encourage rational use of a restricted number of drugs through an understanding of the sources of variation in drug response. This requires communication between clinical pharmacologists, other clinicians, pharmacists, government agencies, and patients. A prescriber's formulary tailored to local needs is an essential component of any plan to improve drug therapy.

Simulated Driving Performance of Adults with ADHD: Comparisons with Alcohol Intoxication

PubMed Central

Weafer, Jessica; Camarillo, Daniel; Fillmore, Mark T.; Milich, Richard; Marczinski, Cecile A.

2015-01-01

Previous research has demonstrated that adults with ADHD are more likely to experience driving-related problems, which suggests that they may exhibit poorer driving performance. However, direct experimental evidence of this hypothesis is limited. The current study involved two experiments that evaluated driving performance in adults with ADHD in terms of the types of driving decrements typically associated with alcohol intoxication. Experiment 1 compared the simulated driving performance of 15 adults with ADHD to 23 adult control participants, who performed the task both while sober and intoxicated. Results showed that sober adults with ADHD exhibited decrements in driving performance compared to sober controls, and that the profile of impairment for the sober ADHD group did in fact resemble that of intoxicated drivers at the BAC level for legally impaired driving in the United States. Driving impairment of the intoxicated individuals was characterized by greater deviation of lane position, faster and more abrupt steering maneuvers, and increased speed variability. Experiment 2 was a dose-challenge study in which 8 adults with ADHD and 8 controls performed the driving simulation task under three doses of alcohol: 0.65 g/kg, 0.45 g/kg, and 0.0 g/kg (placebo). Results showed that driving performance in both groups was impaired in response to alcohol, and that individuals with ADHD exhibited generally poorer driving performance than did controls across all dose conditions. Together the findings provide compelling evidence to suggest that the cognitive and behavioral deficits associated with ADHD might impair driving performance in such a manner as to resemble that of an alcohol intoxicated driver. Moreover, alcohol might impair the performance of drivers with ADHD in an additive fashion that could considerably compromise their driving skill even at blood alcohol concentrations below the legal limit. PMID:18540785

Effect of sex on ethanol consumption and conditioned taste aversion in adolescent and adult rats.

PubMed

Schramm-Sapyta, Nicole L; Francis, Reynold; MacDonald, Andrea; Keistler, Colby; O'Neill, Lauren; Kuhn, Cynthia M

2014-04-01

Vulnerability to alcoholism is determined by many factors, including the balance of pleasurable vs. aversive alcohol-induced sensations: pleasurable sensations increase intake, while aversive sensations decrease it. Female sex and adolescent age are associated with lower sensitivity to intake-reducing effects and more rapid development of alcohol abuse. This study assessed voluntary drinking and the aversive effects of alcohol to determine whether these measures are inversely related across the sexes and development. Voluntary drinking of 20 % ethanol in an every-other-day (EOD) availability pattern and the dose-response relationship of ethanol conditioned taste aversion (CTA) were assessed in male and female adolescent and adult rats. CTA was sex specific in adult but not adolescent rats, with adult females exhibiting less aversion. Voluntary ethanol consumption varied according to age and individual differences but was not sex specific. Adolescents initially drank more than adults, exhibited greater day-to-day variation in consumption, were more susceptible to the alcohol deprivation effect, and took longer to establish individual differences in consumption patterns. These results show that the emergence of intake patterns differs between adolescents and adults. Adolescents as a group initiate drinking at high levels but decrease intake as they mature. A subset of adolescents maintained high drinking levels into adulthood. In contrast, most adults consumed at steady, low levels, but a small subset quickly established and maintained high-consumption patterns. Adolescents also showed marked deprivation-induced increases. Sex differences were not observed in EOD drinking during either adolescence or adulthood.

Radiolysis products and sensory properties of electron-beam-irradiated high-barrier food-packaging films containing a buried layer of recycled low-density polyethylene.

PubMed

Chytiri, S D; Badeka, A V; Riganakos, K A; Kontominas, M G

2010-04-01

The aim was to study the effect of electron-beam irradiation on the production of radiolysis products and sensory changes in experimental high-barrier packaging films composed of polyamide (PA), ethylene-vinyl alcohol (EVOH) and low-density polyethylene (LDPE). Films contained a middle buried layer of recycled LDPE, while films containing 100% virgin LDPE as the middle buried layer were taken as controls. Irradiation doses ranged between zero and 60 kGy. Generally, a large number of radiolysis products were produced during electron-beam irradiation, even at the lower absorbed doses of 5 and 10 kGy (approved doses for food 'cold pasteurization'). The quantity of radiolysis products increased with irradiation dose. There were no significant differences in radiolysis products identified between samples containing a recycled layer of LDPE and those containing virgin LDPE (all absorbed doses), indicating the 'functional barrier' properties of external virgin polymer layers. Sensory properties (mainly taste) of potable water were affected after contact with irradiated as low as 5 kGy packaging films. This effect increased with increasing irradiation dose.

5' UTR polymorphism of dopamine receptor D1 (DRD1) associated with severity and temperament of alcoholism.

PubMed

Kim, Dai-Jin; Park, Byung Lae; Yoon, Sujung; Lee, Hae-Kook; Joe, Keun-Ho; Cheon, Young-Hoon; Gwon, Do-Hoon; Cho, Sung-Nam; Lee, Hye Won; NamGung, Suk; Shin, Hyoung Doo

2007-06-15

Multiple dopamine receptors in the dopaminergic system may be prime candidates for genetic influence on alcohol abuse and dependence due to their involvement in reward and reinforcing mechanisms. Genetic polymorphisms in dopamine receptor genes are believed to influence the development and/or severity of alcoholism. To examine the genetic effects of the Dopamine Receptor D1 (DRD) gene family (DRD1-DRD5) in the Korean population, 11 polymorphisms in the DRD gene family were genotyped and analyzed in 535 alcohol-dependent subjects and 273 population controls. Although none of the polymorphisms of DRD1-5 genes were found to be associated with the risk of alcoholism, one 5' UTR polymorphism in the DRD1 (DRD1-48A>G) gene was significantly associated with severity of alcohol-related problem, as measured by the Alcohol Use Disorders Identification Test (AUDIT) in a gene dose-dependent manner, i.e., 24.37 (+/-8.19) among patients with -48A/A genotype, 22.37 (+/-9.49) among those with -48A/G genotype, and 17.38 (+/-8.28) among those with -48G/G genotype (P=0.002). The genetic effects of DRD1-48A>G were further analyzed with other phenotypes among alcohol-dependent subjects. Interestingly, the DRD1-48A>A genotype was also found to be associated with novelty seeking (NC), harm avoidance (HA), and persistence (P) (P =0.01, 0.02, and 0.003, respectively). The information derived from this study could be valuable for understanding the genetic factors involved in alcoholic phenotypes and genetic distribution of the DRD gene family, and could facilitate further investigation in other ethnic groups.

Effects of Extracts from Tiaozhi Granule and Its Components on Expression of Scavenger Receptor Class B Type I

PubMed Central

Yu, Xiao; Zhao, Xiao-Dong; Bao, Rong-Qi; Yu, Jia-Yu; Zhang, Guo-Xing

2016-01-01

Sera from the rats with different drug treatments (atorvastatin, Tiaozhi granule, or its extracts) were collected. LO-2 cells or HepG2 cells were pretreated with different sera as the following groups randomly: (1) blank control group, (2) positive control group (atorvastatin group), (3) Tiaozhi granule water extract groups, (4) Tiaozhi granule alcohol extract groups, and (5) alcohol extracts for each component: Pollen Typhae Angustifoliae, Curcuma longa L., and Rhizoma Alismatis. LO-2 cells were cotransfected with plasmid carrying SR-BI and pRL-TK promoter genes. Promoter activity was measured by the luciferase reporter gene assay. The mRNA and protein expressions of SR-BI were examined using real-time PCR and western blot analyses. Our results show that promoter activity and mRNA and protein expression levels of the SR-BI were significantly upregulated by Tiaozhi granules alcohol or water extracts in a dose-dependent manner. Pollen Typhae Angustifoliae alcohol extract with a high dosage could also increase SR-BI activity and expression, but not the extracts from Curcuma longa L. and Rhizoma Alismatis. Both Tiaozhi granule alcohol and water extracts can upregulate SR-BI gene expression. Among the components, Pollen Typhae Angustifoliae are important for the regulatory effect coordinating with Curcuma longa L. and Rhizoma Alismatis. PMID:28050195

Alcoholics Anonymous Effectiveness: Faith Meets Science

PubMed Central

Kaskutas, Lee Ann

2009-01-01

Research on the effectiveness of Alcoholics Anonymous (AA) is controversial and is subject to widely divergent interpretations. The goal of this paper is to provide a focused review of the literature on AA effectiveness that will allow readers to judge the evidence for AA effectiveness themselves. The review organizes the research on AA effectiveness according to six criterion required for establishing causation: (1) magnitude of effect; (2) dose response effect; (3) consistent effect; (4) temporally accurate effects; (5) specific effects; (6) plausibility. The evidence for criteria 1, 2, 3, 4 and 6 is very strong: Rates of abstinence are about twice as high among those who attend AA (criteria 1, magnitude); higher levels of attendance are related to higher rates of abstinence (criteria 2, dose-response); these relationships are found for different samples and follow-up periods (criteria 3, consistency); prior AA attendance is predictive of subsequent abstinence (criteria 4, temporal); and mechanisms of action predicted by theories of behavior change are present in AA (criteria 6, plausibility). However, rigorous experimental evidence establishing the specificity of an effect for AA or Twelve Step Facilitation/TSF (criteria 5) is mixed, with 2 trials finding a positive effect for AA, 1 trial finding a negative effect for AA, and 1 trial finding a null effect. Studies addressing specificity using statistical approaches have had two contradictory findings, and two that reported significant effects for AA after adjusting for potential confounders such as motivation to change. PMID:19340677

Rates of Ethanol Metabolism Decrease in Sons of Alcoholics Following a Priming Dose of Ethanol

PubMed Central

Bradford, Blair U.; Jackson, Jennifer K.; Powell, Linda L.; Garbutt, James C.

2007-01-01

Rapid changes in rates of ethanol metabolism in response to acute ethanol administration have been observed in animals and humans. To examine whether this phenomenon might vary by risk for alcoholism, 23 young men with a positive family history of alcoholism (FHP) were compared to 15 young men without a family history of alcoholism (FHN). Rates of ethanol metabolism were measured in all subjects first after an initial ethanol dose (0.85 g/kg) and then, several hours later, a second dose (0.3 g/kg), and the two rates were compared. The two groups of subjects were similar in their histories of ethanol consumption. FHP subjects demonstrated faster initial rates of ethanol metabolism, 148 ± 36 mg/kg/hr, compared to FHN subjects, 124 ± 18 mg/kg/hr, p=.01. However, FHN subjects increased their rate of metabolism by 10 ± 27 percent compared to a decrease of -15 ± 24 percent in FHP subjects, p =.007. Fifty-two percent of the FHP and none of the FHN subjects exhibited a decline in metabolic rate of 20% or more, p=.0008. Since a significant proportion of FHP subjects exhibited a decrease in the second rate of ethanol metabolism, these preliminary data might help to partly explain why FHP individuals differ in their sensitivity to ethanol and are more likely to develop alcohol dependence. PMID:17521843

Age-Dependent Effects of Acute Alcohol Administration in the Hippocampal Phosphoproteome.

PubMed

Contreras, Ana; Morales, Lidia; Tebourbi, Ali; Miguéns, Miguel; Olmo, Nuria Del; Pérez-García, Carmen

2017-12-18

Alcohol consumption during adolescence is deleterious to the developing brain and leads to persistent deficits in adulthood. Several results provide strong evidence for ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the hippocampus. Protein phosphorylation is a well-known and well-documented mechanism in memory processes, but information on phosphoprotein alterations in hippocampus after ethanol exposure is limited. This study focuses on age-related changes in the hippocampal phosphoproteome after acute alcohol administration. We have compared the phosphoprotein expression in the hippocampus of adult and adolescent Wistar rats treated with a single dose of ethanol (5 g/kg i.p.), using a proteomic approach including phosphoprotein enrichment by immobilized metal affinity chromatography (IMAC). Our proteomic analysis revealed that 13 proteins were differentially affected by age, ethanol administration, or both. Most of these proteins are involved in neuroprotection and are expressed less in young rats treated with ethanol. We conclude that acute alcohol induces important changes in the expression of phosphoproteins in the hippocampus that could increase the risk of neurodegenerative disorders, especially when the alcohol exposure begins in adolescence.

Implementing managed alcohol programs in hospital settings: A review of academic and grey literature.

PubMed

Brooks, Hannah L; Kassam, Shehzad; Salvalaggio, Ginetta; Hyshka, Elaine

2018-04-01

People with severe alcohol use disorders are at increased risk of poor acute-care outcomes, in part due to difficulties maintaining abstinence from alcohol while hospitalised. Managed alcohol programs (MAP), which administer controlled doses of beverage alcohol to prevent withdrawal and stabilise drinking patterns, are one strategy for increasing adherence to treatment, and improving health outcomes for hospital inpatients with severe alcohol use disorders. Minimal research has examined the implementation of MAPs in hospital settings. We conducted a scoping review to describe extant literature on MAPs in community settings, as well as the therapeutic provision of alcohol to hospital inpatients, to assess the feasibility of implementing formal MAPs in hospital settings and identify knowledge gaps requiring further study. Four academic and 10 grey literature databases were searched. Evidence was synthesised using quantitative and qualitative approaches. Forty-two studies met review inclusion criteria. Twenty-eight examined the administration of alcohol to hospital inpatients, with most reporting positive outcomes related to prevention or treatment of alcohol withdrawal. Fourteen studies examined MAPs in the community and reported that they help stabilise drinking patterns, reduce alcohol-related harms and facilitate non-judgemental health and social care. MAPs in the community have been well described and research has documented effective provision of alcohol in hospital settings for addressing withdrawal. Implementing MAPs as a harm reduction approach in hospital settings is potentially feasible. However, there remains a need to build off extant literature and develop and evaluate standardised MAP protocols tailored to acute-care settings. © 2018 Australasian Professional Society on Alcohol and other Drugs.

The effects of acute alcohol intoxication on the cognitive mechanisms underlying false facial recognition.

PubMed

Colloff, Melissa F; Flowe, Heather D

2016-06-01

False face recognition rates are sometimes higher when faces are learned while under the influence of alcohol. Alcohol myopia theory (AMT) proposes that acute alcohol intoxication during face learning causes people to attend to only the most salient features of a face, impairing the encoding of less salient facial features. Yet, there is currently no direct evidence to support this claim. Our objective was to test whether acute alcohol intoxication impairs face learning by causing subjects to attend to a salient (i.e., distinctive) facial feature over other facial features, as per AMT. We employed a balanced placebo design (N = 100). Subjects in the alcohol group were dosed to achieve a blood alcohol concentration (BAC) of 0.06 %, whereas the no alcohol group consumed tonic water. Alcohol expectancy was controlled. Subjects studied faces with or without a distinctive feature (e.g., scar, piercing). An old-new recognition test followed. Some of the test faces were "old" (i.e., previously studied), and some were "new" (i.e., not previously studied). We varied whether the new test faces had a previously studied distinctive feature versus other familiar characteristics. Intoxicated and sober recognition accuracy was comparable, but subjects in the alcohol group made more positive identifications overall compared to the no alcohol group. The results are not in keeping with AMT. Rather, a more general cognitive mechanism appears to underlie false face recognition in intoxicated subjects. Specifically, acute alcohol intoxication during face learning results in more liberal choosing, perhaps because of an increased reliance on familiarity.

Evaluation of the Anxiolytic Activity of NR-ANX-C (a Polyherbal Formulation) in Ethanol Withdrawal-Induced Anxiety Behavior in Rats.

PubMed

Mohan, L; Rao, U S C; Gopalakrishna, H N; Nair, V

2011-01-01

The present study investigates the anxiolytic activity of NR-ANX-C, a standardized polyherbal formulation containing the extracts of Withania somnifera, Ocimum sanctum, Camellia sinensis, Triphala, and Shilajit in ethanol withdrawal- (EW-) induced anxiety behavior in rats. Ethanol dependence in rats was produced by substitution of drinking water with 7.5% v/v alcohol for 10 days. Then, ethanol withdrawal was induced by replacing alcohol with drinking water, 12 hours prior to experimentation. After confirming induction of withdrawal symptoms in the alcohol deprived animals, the anxiolytic activity of the test compound in graded doses (10, 20, and 40 mg/kg) was compared to the standard drug alprazolam (0.08 mg/kg) in the elevated plus maze and bright and dark arena paradigms. In our study, single and repeated dose administration of NR-ANX-C reduced EW-induced anxiety in a dose-dependent manner. Even though the anxiolytic activity was not significant at lower doses, NR-ANX-C at the highest dose tested (40 mg/kg) produced significant anxiolytic activity that was comparable to the standard drug alprazolam. Based on our findings we believe that NR-ANX-C has the potential to be used as an alternative to benzodiazepines in the treatment of EW-induced anxiety.

Evaluation of the Anxiolytic Activity of NR-ANX-C (a Polyherbal Formulation) in Ethanol Withdrawal-Induced Anxiety Behavior in Rats

PubMed Central

Mohan, L.; Rao, U. S. C.; Gopalakrishna, H. N.; Nair, V.

2011-01-01

The present study investigates the anxiolytic activity of NR-ANX-C, a standardized polyherbal formulation containing the extracts of Withania somnifera, Ocimum sanctum, Camellia sinensis, Triphala, and Shilajit in ethanol withdrawal- (EW-) induced anxiety behavior in rats. Ethanol dependence in rats was produced by substitution of drinking water with 7.5% v/v alcohol for 10 days. Then, ethanol withdrawal was induced by replacing alcohol with drinking water, 12 hours prior to experimentation. After confirming induction of withdrawal symptoms in the alcohol deprived animals, the anxiolytic activity of the test compound in graded doses (10, 20, and 40 mg/kg) was compared to the standard drug alprazolam (0.08 mg/kg) in the elevated plus maze and bright and dark arena paradigms. In our study, single and repeated dose administration of NR-ANX-C reduced EW-induced anxiety in a dose-dependent manner. Even though the anxiolytic activity was not significant at lower doses, NR-ANX-C at the highest dose tested (40 mg/kg) produced significant anxiolytic activity that was comparable to the standard drug alprazolam. Based on our findings we believe that NR-ANX-C has the potential to be used as an alternative to benzodiazepines in the treatment of EW-induced anxiety. PMID:20953426

Dose-dependent alcohol-induced alterations in chromatin structure persist beyond the window of exposure and correlate with fetal alcohol syndrome birth defects.

PubMed

Veazey, Kylee J; Parnell, Scott E; Miranda, Rajesh C; Golding, Michael C

2015-01-01

In recent years, we have come to recognize that a multitude of in utero exposures have the capacity to induce the development of congenital and metabolic defects. As most of these encounters manifest their effects beyond the window of exposure, deciphering the mechanisms of teratogenesis is incredibly difficult. For many agents, altered epigenetic programming has become suspect in transmitting the lasting signature of exposure leading to dysgenesis. However, while several chemicals can perturb chromatin structure acutely, for many agents (particularly alcohol) it remains unclear if these modifications represent transient responses to exposure or heritable lesions leading to pathology. Here, we report that mice encountering an acute exposure to alcohol on gestational Day-7 exhibit significant alterations in chromatin structure (histone 3 lysine 9 dimethylation, lysine 9 acetylation, and lysine 27 trimethylation) at Day-17, and that these changes strongly correlate with the development of craniofacial and central nervous system defects. Using a neural cortical stem cell model, we find that the epigenetic changes arising as a consequence of alcohol exposure are heavily dependent on the gene under investigation, the dose of alcohol encountered, and that the signatures arising acutely differ significantly from those observed after a 4-day recovery period. Importantly, the changes observed post-recovery are consistent with those modeled in vivo, and associate with alterations in transcripts encoding multiple homeobox genes directing neurogenesis. Unexpectedly, we do not observe a correlation between alcohol-induced changes in chromatin structure and alterations in transcription. Interestingly, the majority of epigenetic changes observed occur in marks associated with repressive chromatin structure, and we identify correlative disruptions in transcripts encoding Dnmt1, Eed, Ehmt2 (G9a), EzH2, Kdm1a, Kdm4c, Setdb1, Sod3, Tet1 and Uhrf1. These observations suggest that the immediate and long-term impacts of alcohol exposure on chromatin structure are distinct, and hint at the existence of a possible coordinated epigenetic response to ethanol during development. Collectively, our results indicate that alcohol-induced modifications to chromatin structure persist beyond the window of exposure, and likely contribute to the development of fetal alcohol syndrome-associated congenital abnormalities.

Effects of Alcohol on the Pharmacokinetics of Blonanserin and N-Deethylated Blonanserin in Healthy Chinese Subjects.

PubMed

Deng, Shuhua; Ni, Xiaojia; Shang, Dewei; Wang, Zhanzhang; Zhang, Ming; Hu, Jinqing; Zhu, Xiuqing; Lu, Haoyang; Chen, Yuqing; Zhang, Yuefeng; Peng, Huan; Wen, Yuguan

2018-04-01

Blonanserin is a novel antipsychotic drug approved for the treatment of schizophrenia in East Asia. The main objective of the present study was to investigate the effect of alcohol on the pharmacokinetic properties of blonanserin and its metabolite N-deethyl blonanserin in healthy Chinese male subjects under fasting conditions. The study was designed as a randomized, open-label, crossover clinical investigation in 10 male volunteers, each of whom received 2 treatments under fasted conditions: treatment A, blonanserin (8 mg) with water, and treatment B, blonanserin (8 mg) with alcohol (1 mL/kg). The average values of areas under the curve (AUCs) and mean peak plasma concentrations (Cmax) were noticeably increased by alcohol consumption. In treatment A, average values of AUC0-24h, AUC0-∞, and Cmax were 3178 ng/h/L, 3879 ng/h/L, and 492 ng/L for blonanserin, and 1932 ng/h/L, 4208 ng/h/L, and 137 ng/L for N-deethylated blonanserin, respectively. In treatment B, AUC0-∞ and Cmax were both increased 2.4-fold for blonanserin and 1.4-fold and 1.7-fold, respectively, for N-deethylated blonanserin (P < 0.05). Compared with treatment A, clearance (Clz/F) of blonanserin and N-deethylated blonanserin decreased significantly (2.4-fold and 1.7-fold, respectively) in treatment B (P < 0.05). Alcohol delayed the absorption and reduced the clearance of blonanserin, leading to a 1.8-fold increase in the time to reach Cmax (Tmax) and half life time (t1/2) (P < 0.05). Alcohol increased the bioavailability of blonanserin and N-deethyl blonanserin in healthy subjects and the marked effect of alcohol on blonanserin bioavailability should be taken into consideration in deciding dosing schedules in clinical therapy.

Acute Alcohol Consumption Elevates Serum Bilirubin, an Endogenous Antioxidant

PubMed Central

O’Malley, Stephanie S.; Gueorguieva, Ralitza; Wu, Ran; Jatlow, Peter I.

2015-01-01

Background Moderate alcohol consumption has been associated with both negative and favorable effects on health. The mechanisms responsible for reported favorable effects remain unclear. Higher (not necessarily elevated) concentrations of serum bilirubin, an antioxidant, have also been associated with reduced risk of cardiovascular disease and all-cause mortality. This study tests the hypothesis that single dose alcohol consumption elevates bilirubin providing a potential link between these observations. Methods 18 healthy individuals (8 cigarette smokers) were administered alcohol, calibrated to achieve blood concentrations of 20, 80 and 120 mg/dL, in random order in 3 laboratory sessions separated by a week. Each session was preceded by and followed by 5–7 days of alcohol abstinence. Serum bilirubin was measured at 7:45 am prior to drinking, at 2 pm, and at 7:45 the next morning. Mixed effects regression models compared baseline and 24 hr. post-drinking bilirubin concentrations. Results Total serum bilirubin (sum of indirect and direct) concentration increased significantly after drinking from baseline to 24 hours in non-smokers (from Mean=0.38, SD=0.24 to Mean=0.51 SD=0.30, F(1, 32.2) =24.24, p<.0001) but not in smokers (from Mean=0.25, SD=0.12 to Mean=0.26, SD=0.15, F(1, 31.1) =0.04, p=0.84). In nonsmokers the indirect bilirubin concentration and the ratio of indirect (unconjugated) to direct (conjugated) bilirubin also increased significantly. Conclusions Alcohol consumption leads to increases in serum bilirubin in nonsmokers. Considering the antioxidant properties of bilirubin, our findings suggest one possible mechanism for the reported association between alcohol consumption and reduced risk of some disorders that could be tested in future longitudinal studies. PMID:25707709

Randomized, double-blind, placebo-controlled clinical trial of choline supplementation in school-aged children with fetal alcohol spectrum disorders.

PubMed

Nguyen, Tanya T; Risbud, Rashmi D; Mattson, Sarah N; Chambers, Christina D; Thomas, Jennifer D

2016-12-01

Prenatal alcohol exposure results in a broad range of cognitive and behavioral impairments. Because of the long-lasting problems that are associated with fetal alcohol spectrum disorders (FASDs), the development of effective treatment programs is critical. Preclinical animal studies have shown that choline, which is an essential nutrient, can attenuate the severity of alcohol-related cognitive impairments. We aimed to translate preclinical findings to a clinical population to investigate whether choline supplementation can ameliorate the severity of memory, executive function, and attention deficits in children with FASDs. In the current study, which was a randomized, double-blind, placebo-controlled clinical trial, we explored the effectiveness of a choline intervention for children with FASDs who were aged 5-10 y. Fifty-five children with confirmed histories of heavy prenatal alcohol exposure were randomly assigned to either the choline (n = 29) or placebo (n = 26) treatment arms. Participants in the choline group received 625 mg choline/d for 6 wk, whereas subjects in the placebo group received an equivalent dose of an inactive placebo treatment. Primary outcomes, including the performance on neuropsychological measures of memory, executive function, and attention and hyperactivity, were assessed at baseline and postintervention. Compared with the placebo group, participants in the choline group did not differentially improve in cognitive performance in any domain. Treatment compliance and mean dietary choline intake were not predictive of treatment outcomes. Findings of the current study do not support that choline, administered at a dose of 625 mg/d for 6 wk, is an effective intervention for school-aged (5-10 y old) children with FASDs. This research provides important information about choline's therapeutic window. Combined with other studies of choline and nutritional interventions in this population, this study emphasizes a further need for the continued study of the role of nutritional status and supplementation in children with FASDs and the contributions of nutrition to neurocognition. This trial was registered at clinicaltrials.gov as NCT01911299. © 2016 American Society for Nutrition.

Randomized, double-blind, placebo-controlled clinical trial of choline supplementation in school-aged children with fetal alcohol spectrum disorders1

PubMed Central

Risbud, Rashmi D; Mattson, Sarah N; Chambers, Christina D; Thomas, Jennifer D

2016-01-01

Background: Prenatal alcohol exposure results in a broad range of cognitive and behavioral impairments. Because of the long-lasting problems that are associated with fetal alcohol spectrum disorders (FASDs), the development of effective treatment programs is critical. Preclinical animal studies have shown that choline, which is an essential nutrient, can attenuate the severity of alcohol-related cognitive impairments. Objective: We aimed to translate preclinical findings to a clinical population to investigate whether choline supplementation can ameliorate the severity of memory, executive function, and attention deficits in children with FASDs. Design: In the current study, which was a randomized, double-blind, placebo-controlled clinical trial, we explored the effectiveness of a choline intervention for children with FASDs who were aged 5–10 y. Fifty-five children with confirmed histories of heavy prenatal alcohol exposure were randomly assigned to either the choline (n = 29) or placebo (n = 26) treatment arms. Participants in the choline group received 625 mg choline/d for 6 wk, whereas subjects in the placebo group received an equivalent dose of an inactive placebo treatment. Primary outcomes, including the performance on neuropsychological measures of memory, executive function, and attention and hyperactivity, were assessed at baseline and postintervention. Results: Compared with the placebo group, participants in the choline group did not differentially improve in cognitive performance in any domain. Treatment compliance and mean dietary choline intake were not predictive of treatment outcomes. Conclusions: Findings of the current study do not support that choline, administered at a dose of 625 mg/d for 6 wk, is an effective intervention for school-aged (5–10 y old) children with FASDs. This research provides important information about choline’s therapeutic window. Combined with other studies of choline and nutritional interventions in this population, this study emphasizes a further need for the continued study of the role of nutritional status and supplementation in children with FASDs and the contributions of nutrition to neurocognition. This trial was registered at clinicaltrials.gov as NCT01911299. PMID:27806977

Discriminative-stimulus effects of zolpidem, triazolam, pentobarbital, and caffeine in zolpidem-trained humans.

PubMed

Rush, C R; Baker, R W; Rowlett, J K

2000-02-01

Six non-drug-abusing humans were trained to discriminate 15 mg zolpidem in the present experiment. After participants acquired discrimination, a range of doses of zolpidem (2.5-15.0 mg), triazolam (0.0625-0.3750 mg), pentobarbital (25-150 mg), caffeine (100-600 mg), and placebo were tested to determine whether they shared discriminative-stimulus effects with 15 mg zolpidem. The participant-rated and performance-impairing effects of zolpidem, triazolam, pentobarbital, and caffeine were assessed concurrently. Triazolam and pentobarbital dose dependently increased zolpidem-appropriate responding. Caffeine occasioned low levels of zolpidem-appropriate responding. Zolpidem, triazolam, and pentobarbital, but not caffeine, generally produced a similar constellation of participant-rated drug effects (e.g., increased scores for the Pentobarbital, Chlorpromazine, and Alcohol Group subscale on the Addiction Research Center Inventory) and dose dependently impaired performance. These results suggest that humans can reliably discriminate zolpidem. Despite its unique benzodiazepine-receptor binding profile, the discriminative-stimulus, participant-rated, and performance-impairing effects of zolpidem are similar to those of the barbiturates and benzodiazepines.

Distraction produces over-additive increases in the degree to which alcohol impairs driving performance

PubMed Central

Van Dyke, Nicholas A.; Fillmore, Mark T.

2015-01-01

Rationale Research indicates that alcohol intoxication and increased demands on drivers’ attention from distractions (e.g. passengers and cell phones) contribute to poor driving performance and increased rates of traffic accidents and fatalities. Objectives The present study examined the separate and combined effects of alcohol and distraction on simulated driving performance at blood alcohol concentrations (BrACs) below the legal driving limit in the United States (i.e. 0.08%). Methods Fifty healthy adult drivers (36 men and 14 women) were tested in a driving simulator following a 0.65 g/kg dose of alcohol and a placebo. Drivers completed two drive tests; a distracted drive, which included a two-choice detection task, and an undistracted control drive. Multiple indicators of driving performance, such as drive speed, within-lane deviation, steering rate, and lane exceedances were measured. Results Alcohol and distraction each impaired measures of driving performance. Moreover, the magnitude of alcohol impairment was increased by at least two-fold when tested under the distracting versus the undistracted condition. Conclusions The findings highlight the need for a clearer understanding of how common distractions impact intoxicated drivers, especially at BrACs that are currently legal for driving in the United States. PMID:26349918

Effects of alcohol on automated and controlled driving performances.

PubMed

Berthelon, Catherine; Gineyt, Guy

2014-05-01

Alcohol is the most frequently detected substance in fatal automobile crashes, but its precise mode of action is not always clear. The present study was designed to establish the influence of blood alcohol concentration as a function of the complexity of the scenarios. Road scenarios implying automatic or controlled driving performances were manipulated in order to identify which behavioral parameters were deteriorated. A single blind counterbalanced experiment was conducted on a driving simulator. Sixteen experienced drivers (25.3 ± 2.9 years old, 8 men and 8 women) were tested with 0, 0.3, 0.5, and 0.8 g/l of alcohol. Driving scenarios varied: road tracking, car following, and an urban scenario including events inspired by real accidents. Statistical analyses were performed on driving parameters as a function of alcohol level. Automated driving parameters such as standard deviation of lateral position measured with the road tracking and car following scenarios were impaired by alcohol, notably with the highest dose. More controlled parameters such as response time to braking and number of crashes when confronted with specific events (urban scenario) were less affected by the alcohol level. Performance decrement was greater with driving scenarios involving automated processes than with scenarios involving controlled processes.

Ethanol suppresses carbamylcholine-induced intracellular calcium oscillation in mouse pancreatic acinar cells.

PubMed

Yoon, Mi Na; Kim, Min Jae; Koong, Hwa Soo; Kim, Dong Kwan; Kim, Se Hoon; Park, Hyung Seo

2017-09-01

Oscillation of intracellular calcium levels is closely linked to initiating secretion of digestive enzymes from pancreatic acinar cells. Excessive alcohol consumption is known to relate to a variety of disorders in the digestive system, including the exocrine pancreas. In this study, we have investigated the role and mechanism of ethanol on carbamylcholine (CCh)-induced intracellular calcium oscillation in murine pancreatic acinar cells. Ethanol at concentrations of 30 and 100 mM reversibly suppressed CCh-induced Ca 2+ oscillation in a dose-dependent manner. Pretreatment of ethanol has no effect on the store-operated calcium entry induced by 10 μM of CCh. Ethanol significantly reduced the initial calcium peak induced by low concentrations of CCh and therefore, the CCh-induced dose-response curve of the initial calcium peak was shifted to the right by ethanol pretreatment. Furthermore, ethanol significantly dose-dependently reduced inositol 1,4,5-trisphosphate-induced calcium release from the internal stores in permeabilized acinar cells. These results provide evidence that excessive alcohol intake could impair cytosolic calcium oscillation through inhibiting calcium release from intracellular stores in mouse pancreatic acinar cells. Copyright © 2017 Elsevier Inc. All rights reserved.

BENZYL ALCOHOL PROTECTS AGAINST ACETAMINOPHEN HEPATOTOXICITY BY INHIBITING CYTOCHROME P450 ENZYMES BUT CAUSES MITOCHONDRIAL DYSFUNCTION AND CELL DEATH AT HIGHER DOSES

PubMed Central

Du, Kuo; McGill, Mitchell R.; Xie, Yuchao; Jaeschke, Hartmut

2015-01-01

Acetaminophen (APAP) hepatotoxicity is a serious public health problem in western countries. Current treatment options for APAP poisoning are limited and novel therapeutic intervention strategies are needed. A recent publication suggested that benzyl alcohol (BA) protects against APAP hepatotoxicity and could serve as a promising antidote for APAP poisoning. To assess the protective mechanisms of BA, C56Bl/6J mice were treated with 400mg/kg APAP and/or 270mg/kg BA. APAP alone caused extensive liver injury at 6h and 24h post-APAP. This injury was attenuated by BA co-treatment. Assessment of protein adduct formation demonstrated that BA inhibits APAP metabolic activation. In support of this, in vitro experiments also showed that BA dose-dependently inhibits cytochrome P450 activities. Correlating with the hepatoprotection of BA, APAP-induced oxidant stress and mitochondrial dysfunction were reduced. Similar results were obtained in primary mouse hepatocytes. Interestingly, BA alone caused mitochondrial membrane potential loss and cell toxicity at high doses, and its protective effect could not be reproduced in primary human hepatocytes (PHH). We conclude that BA protects against APAP hepatotoxicity mainly by inhibiting cytochrome P450 enzymes in mice. Considering its toxic effect and the loss of protection in PHH, BA is not a clinically useful treatment option for APAP overdose patient. PMID:26522885

Regulation of Motivation to Self-Administer Ethanol by mGluR5 in Alcohol-Preferring (P) Rats

PubMed Central

Besheer, Joyce; Faccidomo, Sara; Grondin, Julie J. M.; Hodge, Clyde W.

2008-01-01

Background Emerging evidence indicates that Group I metabotropic glutamate receptors (mGluR1 and mGluR5) differentially regulates ethanol self-administration in several rodent behavioral models. The purpose of this work was to further characterize involvement of Group I mGluRs in the reinforcing effects of ethanol using a progressive ratio schedule of reinforcement. Methods Alcohol-preferring (P) rats were trained to self-administer ethanol (15% v/v) versus water on a concurrent schedule of reinforcement, and the effects of the Group I mGluR antagonists were evaluated on progressive ratio performance. The rats were then trained to self-administer sucrose (0.4% w/v) versus water, and the effects of the antagonists were tested on progressive ratio performance. Results The mGluR1 antagonist, 3,4-dihydro-2H-pyrano[2,3]b quinolin-7-yl (cis-4-methoxy-cyclohexyl) methanone (JNJ 16259685; 0 to 1 mg/kg) and the mGluR5 antagonist, 6-methyl-2-(phenylethynyl) pyridine (MPEP; 0 to 10 mg/kg) dose-dependently reduced ethanol break point. In separate locomotor activity assessments, the lowest effective dose of JNJ 16259685 (0.3 mg/kg) produced a motor impairment, whereas the lowest effective dose of MPEP (3 mg/kg) did not. Thus, the reduction in ethanol break point by mGluR1 antagonism was probably a result of a motor impairment. JNJ 16259685 (0.3 mg/kg) and MPEP (10 mg/kg) reduced sucrose break point and produced motor impairments. Thus, the reductions in sucrose break point produced by both Group I antagonists were probably because of nonspecific effects on motor activity. Conclusions Together, these results suggest that glutamate activity at mGluR5 regulates motivation to self-administer ethanol. PMID:18162077

Effects of Jasminum multiflorum leaf extract on rodent models of epilepsy, motor coordination and anxiety.

PubMed

Addae, Jonas I; Pingal, Ramish; Walkins, Kheston; Cruickshank, Renee; Youssef, Farid F; Nayak, Shivananda B

2017-03-01

Jasmine flowers and leaves are used extensively in folk medicine in different parts of the world to treat a variety of diseases. However, there are very few published reports on the neuropsychiatric effects of Jasmine extracts. Hence, the objectives of the present study were to examine the effects of an alcohol extract of Jasminum multiflorum leaves on topically-applied bicuculline (a model of acute simple partial epilepsy) and maximal electroshock (MES, a model of generalized tonic-clonic seizure) in male Sprague-Dawley rats. The objectives also included an examination of the anxiolytic properties of the extract using an elevated plus maze and the effect of the extract on motor coordination using a rotarod treadmill. Phytochemical analysis of the extract showed the presence of three flavonoids and four additional compounds belonging to the steroid, terpenoid, phenol or sugar classes of compounds. The Jasmine alcohol extract, diluted with water and given orally or intraperitoneally, reduced the number of bicuculline-induced epileptiform discharges in a dose-dependent manner. The extract did not cause a significant increase in the current needed to induce hind limb extension in MES experiments. The extract significantly affected motor coordination when injected at 500mg/kg but not at 200mg/kg. At the latter dose, the extract increased open-arm entries and duration in the elevated plus maze to a level comparable to that of diazepam at 2mg/kg. We conclude that Jasmine leaf extract has a beneficial effect against an animal model of acute partial complex epilepsy, and significant anxiolytic effect at a dose that does not affect motor co-ordination. Copyright © 2017 Elsevier B.V. All rights reserved.

Low Dose Ferrous Gluconate Supplement Fails to Alter the Iron Status of Female Officers-In-Training

DTIC Science & Technology

2005-07-01

guidelines are that total dietary fat intake should contribute no more than 28% of dietary energy with no more than 10% being from saturated fatty...13 3.4 Does alcohol, dietary iron intake , initial iron status or inflammation influence the effect of the supplement...13 3.4.2 Dietary iron intake

Caffeinated beverages and decreased fertility.

PubMed

Wilcox, A; Weinberg, C; Baird, D

104 healthy women who had been attempting to become pregnant for three months were interviewed about their use of caffeinated beverages, alcohol, and cigarettes. In their subsequent cycles, women who consumed more than the equivalent of one cup of coffee per day were half as likely to become pregnant, per cycle, as women who drank less. A dose-response effect was present.

Preservation of Intestinal Structural Integrity by Zinc Is Independent of Metallothionein in Alcohol-Intoxicated Mice

PubMed Central

Lambert, Jason C.; Zhou, Zhanxiang; Wang, Lipeng; Song, Zhenyuan; McClain, Craig J.; Kang, Y. James

2004-01-01

Intestinal-derived endotoxins are importantly involved in alcohol-induced liver injury. Disruption of intestinal barrier function and endotoxemia are common features associated with liver inflammation and injury due to acute ethanol exposure. Zinc has been shown to inhibit acute alcohol-induced liver injury. This study was designed to determine the inhibitory effect of zinc on alcohol-induced endotoxemia and whether the inhibition is mediated by metallothionein (MT) or is independent of MT. MT knockout (MT-KO) mice were administered three oral doses of zinc sulfate (2.5 mg zinc ion/kg body weight) every 12 hours before being administered a single dose of ethanol (6 g/kg body weight) by gavage. Ethanol administration caused liver injury as determined by increased serum transaminases, parenchymal fat accumulation, necrotic foci, and an elevation of tumor necrosis factor (TNF-α). Increased plasma endotoxin levels were detected in ethanol-treated animals whose small intestinal structural integrity was compromised as determined by microscopic examination. Zinc supplementation significantly inhibited acute ethanol-induced liver injury and suppressed hepatic TNF-α production in association with decreased circulating endotoxin levels and a significant protection of small intestine structure. As expected, MT levels remained undetectable in the MT-KO mice under the zinc treatment. These results thus demonstrate that zinc preservation of intestinal structural integrity is associated with suppression of endotoxemia and liver injury induced by acute exposure to ethanol and the zinc protection is independent of MT. PMID:15161632

A potentized homeopathic drug, Arsenicum Album 200, can ameliorate genotoxicity induced by repeated injections of arsenic trioxide in mice.

PubMed

Banerjee, P; Biswas, S J; Belon, P; Khuda-Bukhsh, A R

2007-09-01

Groundwater arsenic contamination has become a menacing global problem. No drug is available until now to combat chronic arsenic poisoning. To examine if a potentized homeopathic remedy, Arsenicum Album-200, can effectively combat chronic arsenic toxicity induced by repeated injections of Arsenic trioxide in mice, the following experimental design was adopted. Mice (Mus musculus) were injected subcutaneously with 0.016% arsenic trioxide at the rate of 1 ml/100 g body weight, at an interval of 7 days until they were killed at day 30, 60, 90 or 120 and were divided into three groups: (i) one receiving a daily dose of Arsenicum Album-200 through oral administration, (ii) one receiving the same dose of diluted succussed alcohol (Alcohol-200) and (iii) another receiving neither drug, nor succussed alcohol. The remedy or the placebo, as the case may be, was fed from the next day onwards after injection until the day before the next injection, and the cycle was repeated until the mice were killed. Two other control groups were also maintained: one receiving only normal diet, and the other receiving normal diet and succussed alcohol. Several toxicity assays, such as cytogenetical (chromosome aberrations, micronuclei, mitotic index, sperm head anomaly) and biochemical (acid and alkaline phosphatases, lipid peroxidation), were periodically made. Compared with controls, the drug fed mice showed reduced toxicity at statistically significant levels in respect of all the parameters studied, thereby indicating protective potentials of the homeopathic drug against chronic arsenic poisoning.

Interaction of alcoholic extracts of hops with cocaine and paracetamol in mice.

PubMed

Horvat, Olga; Raskovic, Aleksandar; Jakovljevic, Vida; Sabo, Jan; Berenji, Janos

2007-01-01

This work describes a study of the interaction in the mouse model of alcoholic extracts of hops of Magnum, Aroma and wild genotypes with drugs that have excitatory effect on the cerebral cortex (cocaine) and analgesic action (paracetamol). Hop drying and preparation of the extracts were carried out according to standard pharmacological procedures for preparing total alcoholic extracts of dry herbs, consisting of one part of dry drug and two parts of 70% alcohol. The mice received four doses i.p. of 0.5% aqueous solutions of the above-mentioned extracts (10 ml/kg) 24, 16, 4 and 0.5 h prior to receiving cocaine (25 mg/kg) or paracetamol (80 mg/kg). The parameter investigated was the change in spontaneous motility of mice after combined treatment with the extracts and cocaine/paracetamol compared to control animals that received the same dose of the drug after treatment with physiological solution. Only the ethanolic extract of Magnum hops increased the spontaneous motility of mice, while none of the extracts showed analgesic action as measured by the hot-plate method. In the interaction with cocaine, the extract of Magnum hops suppressed almost completely the action of cocaine compared to controls. Extracts of the other hops also decreased the cocaine-induced locomotor activity of mice, but to a lesser extent. Hop extracts exhibited a significant pharmacological interaction with paracetamol, with the most pronounced increase in analgesic action being found for the ethanolic extract of Aroma hops and the tert-butanolic extract of wild hops.

A controlled field trial of the effectiveness of phenol and alcohol typhoid vaccines*

PubMed Central

1962-01-01

In order to determine the effectiveness of anti-typhoid vaccines in man a controlled field trial, the first of its kind, was organized in 1954-60 in the town and district of Osijek, Yugoslavia. Heat-killed, phenol-preserved and alcohol-killed, alcohol-preserved anti-typhoid monovaccines were used, with phenolized dysentery vaccine as a control. Some 36000 volunteers were allocated at random into three comparable groups: a phenol-vaccine group, an alcohol-vaccine group and a control group. Immunization consisted of a primary course of two injections. A reinforcing dose was given a year later. The effectiveness of the vaccines was measured by comparing specific morbidity in the three groups, and for greater accuracy only bacteriologically proved typhoid cases were taken into consideration in the statistical analysis. In addition, some 11 000 persons were vaccinated in 1955; these were divided at random into two groups, which received phenolized and alcoholized vaccine respectively; there was no control group. It was found that phenolized vaccine gave relatively high protection while alcoholized vaccine was of little, if any, efficacy. The efficacy of phenolized vaccine was of rather long duration. These field results obtained on man are not in agreement with the results of laboratory tests known at present. Neither laboratory assays on mice nor serological tests on man could be correlated with the results of the field trial. For this reason further studies are necessary in order to determine the value of various other types of anti-typhoid vaccines and to develop reliable laboratory tests for the measurement of the potency of anti-typhoid vaccines. PMID:20604110

ROLES OF OPIOID RECEPTOR SUBTYPES IN MEDIATING ALCOHOL SEEKING INDUCED BY DISCRETE CUES AND CONTEXT

PubMed Central

Marinelli, Peter W.; Funk, Douglas; Harding, Stephen; Li, Zhaoxia; Juzytsch, Walter; Lê, A.D.

2009-01-01

The aim of this study was to assess the effects of selective blockade of the delta (DOP) or mu opioid (MOP) receptors on alcohol seeking induced by discrete cues and context. In Experiment 1, rats were trained to self-administer alcohol in an environment with distinct sensory properties. After extinction in a different context with separate sensory properties, rats were tested for context-induced renewal in the original context following treatment with the DOP receptor antagonist naltrindole (0 – 15-mg/kg, IP) or the MOP receptor antagonist CTOP (0 – 3-µg/kg ICV). In a separate set of experiments, reinstatement was tested with the presentation of a discrete light+tone cue previously associated with alcohol delivery, following extinction without the cue. In Experiment 2, the effects of naltrindole (0 – 5-mg/kg, IP) or CTOP (0 – 3-µg/kg µg ICV) were assessed. For context-induced renewal, 7.5-mg/kg naltrindole reduced responding without affecting locomotor activity. Both doses of CTOP attenuated responding in the first 15 min of the renewal test session; however, total responses did not differ at the end of the session. For discrete cue-induced reinstatement, 1 and 5-mg/kg naltrindole attenuated responding, but CTOP had no effect. We conclude that while DOP receptors mediate alcohol seeking induced by discrete cues and context, MOP receptors may play a modest role only in context-induced renewal. These findings point to a differential involvement of opioid receptor subtypes in the effects of different kinds of conditioned stimuli on alcohol seeking, and support a more prominent role for DOP receptors. PMID:19686472

Use of cough and cold preparations during breastfeeding.

PubMed

Mitchell, J L

1999-12-01

Adverse reactions in infants from maternal drug ingestion depend largely on the amount of milk consumed by the infant, timing of breastfeeding in relation to dosing, dose of the medication, dosing interval, and duration of therapy. When taking medications, breastfeeding mothers should be instructed to take their medication after breastfeeding, at the lowest effective dose and for the shortest duration. Overall, there are few data from human studies on the use of antihistamines, decongestants, and cough products during breastfeeding. Studies of pseudoephedrine, triprolidine, and loratadine in humans conclude that low levels of each drug would reach a breastfed infant. Since triprolidine and pseudoephedrine are also considered compatible with breastfeeding by the AAP, these 2 drugs should be the first-line choices. Codeine is considered compatible with breastfeeding by the AAP, and would be an acceptable choice for short-term use as a cough suppressant. It is important to note that many of the liquid cough and cold products contain alcohol. In addition, many of the combination products are a mixture of an antihistamine and a decongestant and may also contain aspirin, acetaminophen, ibuprofen, or caffeine. It is preferable for nursing mothers to only take medications that are necessary and to avoid such combination products. The AAP considers alcohol, acetaminophen, ibuprofen, and caffeine compatible with breastfeeding. Aspirin has been associated with significant negative effects on some nursing infants, and the AAP recommends giving aspirin to nursing mothers with caution. Mothers taking cough and cold products should watch for adverse events in their breastfed infants. Infants may experience paradoxical central nervous stimulation from antihistamines and irritability and insomnia from decongestants.

Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury

PubMed Central

Wang, Yuhua; Liu, Yanlong; Sidhu, Anju; Ma, Zhenhua; McClain, Craig

2012-01-01

Endotoxemia is a contributing cofactor to alcoholic liver disease (ALD), and alcohol-induced increased intestinal permeability is one of the mechanisms of endotoxin absorption. Probiotic bacteria have been shown to promote intestinal epithelial integrity and protect barrier function in inflammatory bowel disease (IBD) and in ALD. Although it is highly possible that some common molecules secreted by probiotics contribute to this action in IBD, the effect of probiotic culture supernatant has not yet been studied in ALD. We examined the effects of Lactobacillus rhamnosus GG culture supernatant (LGG-s) on the acute alcohol-induced intestinal integrity and liver injury in a mouse model. Mice on standard chow diet were supplemented with supernatant from LGG culture (109 colony-forming unit/mouse) for 5 days, and one dose of alcohol at 6 g/kg body wt was administered via gavage. Intestinal permeability was measured by FITC-FD-4 ex vivo. Alcohol-induced liver injury was examined by measuring the activity of alanine aminotransferase (ALT) in plasma, and liver steatosis was evaluated by triglyceride content and Oil Red O staining of the liver sections. LGG-s pretreatment restored alcohol-induced reduction in ileum mRNA levels of claudin-1, intestine trefoil factor (ITF), P-glycoprotein (P-gp), and cathelin-related antimicrobial peptide (CRAMP), which play important roles on intestinal barrier integrity. As a result, LGG-s pretreatment significantly inhibited the alcohol-induced intestinal permeability, endotoxemia and subsequently liver injury. Interestingly, LGG-s pretreatment increased ileum mRNA expression of hypoxia-inducible factor (HIF)-2α, an important transcription factor of ITF, P-gp, and CRAMP. These results suggest that LGG-s ameliorates the acute alcohol-induced liver injury by promoting HIF signaling, leading to the suppression of alcohol-induced increased intestinal permeability and endotoxemia. The use of bacteria-free LGG culture supernatant provides a novel strategy for prevention of acute alcohol-induced liver injury. PMID:22538402

Tiliacora triandra, an Anti-Intoxication Plant, Improves Memory Impairment, Neurodegeneration, Cholinergic Function, and Oxidative Stress in Hippocampus of Ethanol Dependence Rats.

PubMed

Phunchago, Nattaporn; Wattanathorn, Jintanaporn; Chaisiwamongkol, Kowit

2015-01-01

Oxidative stress plays an important role in brain dysfunctions induced by alcohol. Since less therapeutic agent against cognitive deficit and brain damage induced by chronic alcohol consumption is less available, we aimed to assess the effect of Tiliacora triandra extract, a plant possessing antioxidant activity, on memory impairment, neuron density, cholinergic function, and oxidative stress in hippocampus of alcoholic rats. Male Wistar rats were induced ethanol dependence condition by semivoluntary intake of alcohol for 15 weeks. Alcoholic rats were orally given T. triandra at doses of 100, 200, and 400 mg·kg(-1)BW for 14 days. Memory assessment was performed every 7 days while neuron density, activities of AChE, SOD, CAT, and GSH-Px and, MDA level in hippocampus were assessed at the end of study. Interestingly, the extract mitigated the increased escape latency, AChE and MDA level. The extract also mitigated the decreased retention time, SOD, CAT, and GSH-Px activities, and neurons density in hippocampus induced by alcohol. These data suggested that the extract improved memory deficit in alcoholic rats partly via the decreased oxidative stress and the suppression of AChE. Therefore, T. triandra is the potential reagent for treating brain dysfunction induced by alcohol. However, further researches are necessary to understand the detail mechanism and possible active ingredient.

Acetaldehyde reinforcement and motor reactivity in newborns with or without a prenatal history of alcohol exposure

PubMed Central

March, Samanta M.; Culleré, Marcela E.; Abate, Paula; Hernández, José I.; Spear, Norman E.; Molina, Juan C.

2013-01-01

Animal models have shown that early ontogeny seems to be a period of enhanced affinity to ethanol. Interestingly, the catalase system that transforms ethanol (EtOH) into acetaldehyde (ACD) in the brain, is more active in the perinatal rat compared to adults. ACD has been found to share EtOH's behavioral effects. The general purpose of the present study was to assess ACD motivational and motor effects in newborn rats as a function of prenatal exposure to EtOH. Experiment 1 evaluated if ACD (0.35 μmol) or EtOH (0.02 μmol) supported appetitive conditioning in newborn pups prenatally exposed to EtOH. Experiment 2 tested if prenatal alcohol exposure modulated neonatal susceptibility to ACD's motor effects (ACD dose: 0, 0.35 and 0.52 μmol). Experiment 1 showed that EtOH and ACD supported appetitive conditioning independently of prenatal treatments. In Experiment 2, latency to display motor activity was altered only in neonates prenatally treated with water and challenged with the highest ACD dose. Prenatal EtOH experience results in tolerance to ACD's motor activity effects. These results show early susceptibility to ACD's appetitive effects and attenuation of motor effects as a function of prenatal history with EtOH, within a stage in development where brain ACD production seems higher than later in life. PMID:23785319

Alcohol-Induced Impairment of Balance is Antagonized by Energy Drinks.

PubMed

Marczinski, Cecile A; Fillmore, Mark T; Stamates, Amy L; Maloney, Sarah F

2018-01-01

The acute administration of alcohol reliably impairs balance and motor coordination. While it is common for consumers to ingest alcohol with other stimulant drugs (e.g., caffeine, nicotine), little is known whether prototypical alcohol-induced balance impairments are altered by stimulant drugs. The purpose of this study was to examine whether the coadministration of a high-caffeine energy drink with alcohol can antagonize expected alcohol-induced increases in body sway. Sixteen social drinkers (of equal gender) participated in 4 separate double-blind dose administration sessions that involved consumption of alcohol and energy drinks, alone and in combination. Following dose administration, participants completed automated assessments of balance stability (both eyes open and eyes closed) measured using the Biosway Portable Balance System. Participants completed several subjective measures including self-reported ratings of sedation, stimulation, fatigue, and impairment. Blood pressure and pulse rate were recorded repeatedly. The acute administration of alcohol increased body sway, and the coadministration of energy drinks antagonized this impairment. When participants closed their eyes, alcohol-induced body sway was similar whether or not energy drinks were ingested. While alcohol administration increased ratings of sedation and fatigue, energy drink administration increased ratings of stimulation and reduced ratings of fatigue. Modest increases in systolic and diastolic blood pressure following energy drink administration were also observed. Visual assessment of balance impairment is frequently used to indicate that an individual has consumed too much alcohol (e.g., as part of police-standardized field sobriety testing or by a bartender assessing when someone should no longer be served more alcohol). The current findings suggest that energy drinks can antagonize alcohol-induced increases in body sway, indicating that future work is needed to determine whether this observation regarding neuromotor functioning applies to alcohol in combination with all types of stimulant drugs. Copyright © 2017 by the Research Society on Alcoholism.

Ethanol impairs activation of retinoic acid receptors in cerebellar granule cells in a rodent model of fetal alcohol spectrum disorders.

PubMed

Kumar, Ambrish; Singh, Chandra K; DiPette, Donald D; Singh, Ugra S

2010-05-01

Ethanol is the main addictive and neurotoxic constituent of alcohol. Ethanol exposure during embryonic development causes dysfunction of the central nervous system (CNS) and leads to fetal alcohol spectrum disorders. The cerebellum is one of the CNS regions that are particularly vulnerable to ethanol toxic effects. Retinoic acid (RA) is a physiologically active metabolite of vitamin A that is locally synthesized in the cerebellum. Studies have shown that RA is required for neuronal development, but it remains unknown if ethanol impairs RA signaling and thus induces neuronal malformations. In this study, we tested the hypothesis that ethanol impairs the expression and activation of RA receptors in cerebellum and in cerebellar granule cells. The cerebellum of ethanol unexposed and exposed pups was used to study the expression of retinoic acid receptors (RARs or RXRs) by immunohistochemistry and by Western blot analysis. We also studied the effect of ethanol on expression of RA receptors in the cerebellar granule cells. Activation of RA receptors (DNA-binding activities) in response to high-dose ethanol was determined by electrophoretic mobility shift and supershift assays. Findings from these studies demonstrated that ethanol exposure reduced the expression of RARalpha/gamma while it increased the expression of RXRalpha/gamma in the cerebellum and in cerebellar granule neurons. Immuno-histological studies further strengthened the expression pattern of RA receptors in response to ethanol. The DNA-binding activity of RARs was reduced, while DNA-binding activity of RXRs was increased in response to ethanol exposure. For the first time, our studies have demonstrated that high-dose ethanol affects the expression and activation of RA receptors, which could impair the signaling events and induce harmful effects on the survival and differentiation of cerebellar granule cells. Taken together, these findings could provide insight into the treatment options for brain defects caused by excessive ethanol exposure, such as in Fetal Alcohol Spectrum Disorders.

Pharmacotherapy for Alcohol Dependence: The 2015 Recommendations of the French Alcohol Society, Issued in Partnership with the European Federation of Addiction Societies.

PubMed

Rolland, Benjamin; Paille, François; Gillet, Claudine; Rigaud, Alain; Moirand, Romain; Dano, Corine; Dematteis, Maurice; Mann, Karl; Aubin, Henri-Jean

2016-01-01

The latest French good practice recommendations (GPRs) for the screening, prevention, and treatment of alcohol misuse were recently published in partnership with the European Federation of Addiction Societies (EUFAS). This article aims to synthesize the GPRs focused on the pharmacotherapy of alcohol dependence. A four-member European steering committee defined the questions that were addressed to an 18-member multiprofessional working group (WG). The WG developed the GPRs based on a systematic, hierarchical, and structured literature search and submitted the document to two review processes involving 37 French members from multiple disciplines and 5 non-French EUFAS members. The final GPRs were graded A, B, or C, or expert consensus (EC) using a reference recommendation grading system. The treatment of alcohol dependence consists of either alcohol detoxification or abstinence maintenance programs or drinking reduction programs. The therapeutic objective is the result of a decision made jointly by the physician and the patient. For alcohol detoxification, benzodiazepines (BZDs) are recommended in first-line (grade A). BZD dosing should be guided by regular clinical monitoring (grade B). Residential detoxification is more appropriate for patients with a history of seizures, delirium tremens, unstable psychiatric comorbidity, or another associated substance use disorder (grade B). BZDs are only justified beyond a 1-week period in the case of persistent withdrawal symptoms, withdrawal events or associated BZD dependence (grade B). BZDs should not be continued for more than 4 weeks (grade C). The dosing and duration of thiamine (vitamin B1) during detoxification should be adapted to nutritional status (EC). For relapse prevention, acamprosate and naltrexone are recommended as first-line medications (grade A). Disulfiram can be proposed as second-line option in patients with sufficient information and supervision (EC). For reducing alcohol consumption, nalmefene is indicated in first line (grade A). The second-line prescription of baclofen, up to 300 mg/day, to prevent relapse or reduce drinking should be carried out according to the "temporary recommendation for use" measure issued by the French Health Agency (EC). During pregnancy, abstinence is recommended (EC). If alcohol detoxification is conducted during pregnancy, BZD use is recommended (grade B). No medication other than those for alcohol detoxification should be initiated in pregnant or breastfeeding women (EC). In a stabilized pregnant patient taking medication to support abstinence, the continuation of the drug should be considered on a case-by-case basis, weighing the benefit/risk ratio. Only disulfiram should be always stopped, given the unknown risks of the antabuse effect on the fetus (EC). First-line treatments to help maintain abstinence or reduce drinking are off-label for people under 18 years of age and should thus be considered on a case-by-case basis after the repeated failure of psychosocial measures alone (EC). Short half-life BZDs should be preferred for the detoxification of elderly patients (grade B). The initial doses of BZDs should be reduced by 30 to 50% in elderly patients (EC). In patients with chronic alcohol-related physical disorders, abstinence is recommended (EC). Any antidepressant or anxiolytic medication should be introduced after a psychiatric reassessment after 2-4 weeks of alcohol abstinence or low-risk use (grade B). A smoking cessation program should be offered to any smokers involved in an alcohol treatment program (grade B). © 2015 John Wiley & Sons Ltd.

Treatment of the alcoholic organic brain syndrome: double-blind, placebo-controlled clinical, psychometric and electroencephalographic mapping studies with modafinil.

PubMed

Saletu, B; Saletu, M; Grünberger, J; Frey, R; Anderer, P; Mader, R

1993-01-01

In a double-blind study 40 abstinent hospitalized male patients with an alcoholic organic brain syndrome (OBS; ICD 9: 291.2) were treated for 6 weeks with either placebo or 200 mg modafinil b.i.d. Modafinil (CRL 40476) is a vigilance-promoting, putative central alpha 1-adrenergic agonist with a pharmacological profile quite different from that of amphetamine. Clinical investigations demonstrated that the spontaneous remission of the alcoholic OBS was augmented and accelerated by modafinil, which was found significant as compared with placebo by confirmatory statistics in the target variable, the Clinical Global Impression scale. The drug was well tolerated. Psychometric tests revealed significant improvement of the noopsyche after modafinil as compared with placebo, while the thymopsyche and psychophysiological measurements were not affected. Electroencephalographic mapping showed significant differences between the central effects of modafinil and placebo indicating an improvement of vigilance under modafinil. Typical vigilance-promoting properties were seen after acute drug administration, were less evident before the morning dose after chronic treatment but re-occurred after super-imposed daily drug administration. Thus, our clinical, psychometric and neurophysiological investigations in alcoholic OBS patients demonstrated a therapeutic effect of modafinil in the early phase of abstinence.

Low and moderate prenatal ethanol exposures of mice during gastrulation or neurulation delays neurobehavioral development.

PubMed

Schambra, Uta B; Goldsmith, Jeff; Nunley, Kevin; Liu, Yali; Harirforoosh, Sam; Schambra, Heidi M

2015-01-01

Human and animal studies show significant delays in neurobehavioral development in offspring after prolonged prenatal exposure to moderate and high ethanol doses resulting in high blood alcohol concentration (BECs). However, none have investigated the effects of lower ethanol doses given acutely during specific developmental time periods. Here, we sought to create a mouse model for modest and circumscribed human drinking during the 3rd and 4th weeks of pregnancy. We acutely treated mice during embryo gastrulation on gestational day (GD) 7 or neurulation on GD8 with a low or moderate ethanol dose given via gavage that resulted in BECs of 107 and 177 mg/dl, respectively. We assessed neonatal physical development (pinnae unfolding, and eye opening); weight gain from postnatal day (PD) 3-65; and neurobehavioral maturation (pivoting, walking, cliff aversion, surface righting, vertical screen grasp, and rope balance) from PD3 to 17. We used a multiple linear regression model to determine the effects of dose, sex, day of treatment and birth in animals dosed during gastrulation or neurulation, relative to their vehicle controls. We found that ethanol exposure during both time points (GD7 and GD8) resulted in some delays of physical development and significant sensorimotor delays of pivoting, walking, and thick rope balance, as well as additional significant delays in cliff aversion and surface righting after GD8 treatment. We also found that treatment with the low ethanol dose more frequently affected neurobehavioral development of the surviving pups than treatment with the moderate ethanol dose, possibly due to a loss of severely affected offspring. Finally, mice born prematurely were delayed in their physical and sensorimotor development. Importantly, we showed that brief exposure to low dose ethanol, if administered during vulnerable periods of neuroanatomical development, results in significant neurobehavioral delays in neonatal mice. We thus expand concerns about alcohol consumption during the 3rd and 4th weeks of human pregnancy to include occasional light to moderate drinking. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of electron beam irradiation on the structural properties of poly(vinyl alcohol) formulations with triphenyl tetrazolium chloride dye (TTC)

NASA Astrophysics Data System (ADS)

Ali, Z. I.; Said, Hossam M.; Ali, H. E.

2006-01-01

Films of poly(vinyl alcohol) (PVA) composites with triphenyl tetrazolium chloride (TTC) dye were prepared and exposed to various radiation doses delivered by accelerated electrons. The results showed that at a low dose of 50 kGy, the colour difference (Δ E*) of PVA/TTC films was increased by ˜10 times of the initial value. However, the change in colour differences did not go systematically with increasing the TTC content, in which the composite with 1.5 wt% displayed higher value than that with 3.5 wt%. The differential scanning calorimetry (DSC) showed that the presence of the TTC dye caused a depression in the melting point ( Tm) and heat of fusion (Δ Hf) of the PVA bulk polymer. However, the thermogravimetric analysis (TGA) showed that the presence of the TTC dye improved the thermal stability of PVA. Also, the tensile strength at break of PVA/TTC composites was improved after electron beam irradiation.

Rat strain differences in brain structure and neurochemistry in response to binge alcohol.

PubMed

Zahr, Natalie M; Mayer, Dirk; Rohlfing, Torsten; Hsu, Oliver; Vinco, Shara; Orduna, Juan; Luong, Richard; Bell, Richard L; Sullivan, Edith V; Pfefferbaum, Adolf

2014-01-01

Ventricular enlargement is a robust phenotype of the chronically dependent alcoholic human brain, yet the mechanism of ventriculomegaly is unestablished. Heterogeneous stock Wistar rats administered binge EtOH (3 g/kg intragastrically every 8 h for 4 days to average blood alcohol levels (BALs) of 250 mg/dL) demonstrate profound but reversible ventricular enlargement and changes in brain metabolites (e.g., N-acetylaspartate (NAA) and choline-containing compounds (Cho)). Here, alcohol-preferring (P) and alcohol-nonpreferring (NP) rats systematically bred from heterogeneous stock Wistar rats for differential alcohol drinking behavior were compared with Wistar rats to determine whether genetic divergence and consequent morphological and neurochemical variation affect the brain's response to binge EtOH treatment. The three rat lines were dosed equivalently and approached similar BALs. Magnetic resonance imaging and spectroscopy evaluated the effects of binge EtOH on brain. As observed in Wistar rats, P and NP rats showed decreases in NAA. Neither P nor NP rats, however, responded to EtOH intoxication with ventricular expansion or increases in Cho levels as previously noted in Wistar rats. Increases in ventricular volume correlated with increases in Cho in Wistar rats. The latter finding suggests that ventricular volume expansion is related to adaptive changes in brain cell membranes in response to binge EtOH. That P and NP rats responded differently to EtOH argues for intrinsic differences in their brain cell membrane composition. Further, differential metabolite responses to EtOH administration by rat strain implicate selective genetic variation as underlying heterogeneous effects of chronic alcoholism in the human condition.

The relationship between alcohol consumption and vascular complications and mortality in individuals with type 2 diabetes.

PubMed

Blomster, Juuso I; Zoungas, Sophia; Chalmers, John; Li, Qiang; Chow, Clara K; Woodward, Mark; Mancia, Giuseppe; Poulter, Neil; Williams, Bryan; Harrap, Stephen; Neal, Bruce; Patel, Anushka; Hillis, Graham S

2014-01-01

Moderate alcohol consumption has been associated with a reduced risk of mortality and coronary artery disease. The relationship between cardiovascular health and alcohol use in type 2 diabetes is less clear. The current study assesses the effects of alcohol use among participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial. The effects of alcohol use were explored using Cox regression models, adjusted for potential confounders. The study end points were cardiovascular events (cardiovascular death, myocardial infarction, and stroke), microvascular complications (new or worsening nephropathy or retinopathy), and all-cause mortality. During a median of 5 years of follow-up, 1,031 (9%) patients died, 1,147 (10%) experienced a cardiovascular event, and 1,136 (10%) experienced a microvascular complication. Compared with patients who reported no alcohol consumption, those who reported moderate consumption had fewer cardiovascular events (adjusted hazard ratio [aHR] 0.83; 95% CI 0.72-0.95; P = 0.008), less microvascular complications (aHR 0.85; 95% CI 0.73-0.99; P = 0.03), and lower all-cause mortality (aHR 0.87; 96% CI 0.75-1.00; P = 0.05). The benefits were particularly evident in participants who drank predominantly wine (cardiovascular events aHR 0.78, 95% CI 0.63-0.95, P = 0.01; all-cause mortality aHR 0.77, 95% CI 0.62-0.95, P = 0.02). Compared with patients who reported no alcohol consumption, those who reported heavy consumption had dose-dependent higher risks of cardiovascular events and all-cause mortality. In patients with type 2 diabetes, moderate alcohol use, particularly wine consumption, is associated with reduced risks of cardiovascular events and all-cause mortality.

Nalmefene for the management of alcohol dependence: review on its pharmacology, mechanism of action and meta-analysis on its clinical efficacy.

PubMed

Mann, Karl; Torup, Lars; Sørensen, Per; Gual, Antoni; Swift, Robert; Walker, Brendan; van den Brink, Wim

2016-12-01

Nalmefene, a mu- and delta-opioid receptor (MOR, DOR) antagonist and a partial kappa-opioid receptor (KOR) agonist, is approved in the European Union and other countries for the reduction of alcohol consumption in alcohol dependent patients with a high drinking risk level according to WHO ("target population"). This review presents an overview of nalmefene׳s pharmacology, its mechanisms of action and a meta-analysis on its efficacy in reducing alcohol consumption. The review was based on a systematic search of the literature. Random effects meta-analyses were performed on published and unpublished trials directed at drinking reduction using the changes in heavy drinking days (HDDs) and daily total alcohol consumption (TAC) from baseline to the primary endpoint. For each included study and each dose, Hedges' g was used as an unbiased estimator of the standardised mean differences between nalmefene and placebo. Preclinical data suggests that nalmefene counters alcohol-induced dysregulations of the MOR/endorphine and the KOR/dynorphin system. Evidence further suggests that reduced alcohol consumption is an effective treatment strategy that appeals to patients not ready for abstinence. Finally, meta-analyses confirmed the efficacy of 20mg nalmefene for reducing HDDs in the ITT population (Hedge׳s g=-0.20; 95% CI -0.30 to -0.09) and the target population (Hedge׳s g=-0.33; 95% CI -0.48 to -0.18). Similar results were seen for TAC. Several meta-analyses, including this new meta-analysis, support nalmefene׳s efficacy in reducing alcohol consumption. In conclusion, because it does not require abstinence, this treatment has the potential to motivate more patients for treatment and thus helps to address a major public health concern. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Effects of binge drinking and hangover on response selection sub-processes-a study using EEG and drift diffusion modeling.

PubMed

Stock, Ann-Kathrin; Hoffmann, Sven; Beste, Christian

2017-09-01

Effects of binge drinking on cognitive control and response selection are increasingly recognized in research on alcohol (ethanol) effects. Yet, little is known about how those processes are modulated by hangover effects. Given that acute intoxication and hangover seem to be characterized by partly divergent effects and mechanisms, further research on this topic is needed. In the current study, we hence investigated this with a special focus on potentially differential effects of alcohol intoxication and subsequent hangover on sub-processes involved in the decision to select a response. We do so combining drift diffusion modeling of behavioral data with neurophysiological (EEG) data. Opposed to common sense, the results do not show an impairment of all assessed measures. Instead, they show specific effects of high dose alcohol intoxication and hangover on selective drift diffusion model and EEG parameters (as compared to a sober state). While the acute intoxication induced by binge-drinking decreased the drift rate, it was increased by the subsequent hangover, indicating more efficient information accumulation during hangover. Further, the non-decisional processes of information encoding decreased with intoxication, but not during hangover. These effects were reflected in modulations of the N2, P1 and N1 event-related potentials, which reflect conflict monitoring, perceptual gating and attentional selection processes, respectively. As regards the functional neuroanatomical architecture, the anterior cingulate cortex (ACC) as well as occipital networks seem to be modulated. Even though alcohol is known to have broad neurobiological effects, its effects on cognitive processes are rather specific. © 2016 Society for the Study of Addiction.