Sample records for abuse including ethanol

  1. Intermittent ethanol access schedule in rats as a preclinical model of alcohol abuse

    PubMed Central

    Carnicella, Sebastien; Ron, Dorit; Barak, Segev

    2014-01-01

    One of the major challenges in preclinical studies of alcohol abuse and dependence remains the development of paradigms that will elicit high ethanol intake and mimic the progressive transition from low or moderate social drinking to excessive alcohol consumption. Exposure of outbred rats to repeated cycles of free-choice ethanol intake and withdrawal with the use of intermittent access to 20% ethanol in a 2-bottle choice procedure (IA2BC) has been shown to induce a gradual escalation of voluntary ethanol intake and preference, eventually reaching ethanol consumption levels of 5–6 g/kg/24 h, and inducing pharmacologically relevant blood ethanol concentrations (BECs). This procedure has recently been gaining popularity due to its simplicity, high validity, and reliable outcomes. Here we review experimental and methodological data related to IA2BC, and discuss the usefulness and advantages of this procedure as a valuable pre-training method for initiating operant ethanol self-administration of high ethanol intake, as well as conditioned place preference (CPP). Despite some limitations, we provide evidence that IA2BC and related operant procedures provide the possibility to operationalize multiple aspects of alcohol abuse and addiction in a rat model, including transition from social-like drinking to excessive alcohol consumption, binge drinking, alcohol seeking, relapse, and neuroadaptations related to excessive alcohol intake. Hence, IA2BC appears to be a useful and relevant procedure for preclinical evaluation of potential therapeutic approaches against alcohol abuse disorders. PMID:24721195

  2. Intermittent ethanol access schedule in rats as a preclinical model of alcohol abuse.

    PubMed

    Carnicella, Sebastien; Ron, Dorit; Barak, Segev

    2014-05-01

    One of the major challenges in preclinical studies of alcohol abuse and dependence remains the development of paradigms that will elicit high ethanol intake and mimic the progressive transition from low or moderate social drinking to excessive alcohol consumption. Exposure of outbred rats to repeated cycles of free-choice ethanol intake and withdrawal with the use of intermittent access to 20% ethanol in a 2-bottle choice procedure (IA2BC) has been shown to induce a gradual escalation of voluntary ethanol intake and preference, eventually reaching ethanol consumption levels of 5-6 g/kg/24 h, and inducing pharmacologically relevant blood ethanol concentrations (BECs). This procedure has recently been gaining popularity due to its simplicity, high validity, and reliable outcomes. Here we review experimental and methodological data related to IA2BC, and discuss the usefulness and advantages of this procedure as a valuable pre-training method for initiating operant ethanol self-administration of high ethanol intake, as well as conditioned place preference (CPP). Despite some limitations, we provide evidence that IA2BC and related operant procedures provide the possibility to operationalize multiple aspects of alcohol abuse and addiction in a rat model, including transition from social-like drinking to excessive alcohol consumption, binge drinking, alcohol seeking, relapse, and neuroadaptations related to excessive alcohol intake. Hence, IA2BC appears to be a useful and relevant procedure for preclinical evaluation of potential therapeutic approaches against alcohol abuse disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Decreased IGF-I bioavailability after ethanol abuse in alcoholics: partial restitution after short-term abstinence.

    PubMed

    Röjdmark, S; Brismar, K

    2001-01-01

    IGF-I stimulates protein synthesis, lowers blood glucose, and affects cell differentiation. The main production site of IGF-I is the liver. One of its binding proteins, IGFBP-1, is also produced by the liver. It is well known that ethanol affects the function of the human liver. Long-term alcohol abuse may therefore not only cause considerable IGF-I and IGFBP-1 production changes, but also changes in IGF-I bioavailability, which at least in part is determined by the IGF-I/IGFBP-1 ratio. Not much is known about how the bioavailability of IGF-I is changed in alcohol abusers. Therefore, the objective of this investigation was to study that matter, and to elucidate how abstinence affects IGF-I bioavailability in man. Three study groups were formed: group N including normal non-addicted subjects, group E ethanol abusers without gross liver insufficiency, and group C alcohol abusers with liver cirrhosis and ascites. Serum concentrations of insulin, GH, IGF-1, and IGFBP-1 were determined in the morning in all participants, and the IGF-I/IGFBP-1 ratios were calculated. These values were compared in the three study groups. In group E comparison was also made between values recorded in the ethanol intoxicated and in the detoxicated states. Patients in group C had low IGF-I levels, high IGFBP-1 levels, and low IGF-I bioavailability as reflected by the IGF-I/IGFBP-1 ratios, which were several-fold reduced compared with subjects in group N (0.6+/-0.2 vs 10.2+/-2.3; p<0.001). Patients in group E had also a low IGF-I/IGFBP-1 ratio in the acute ethanol intoxicated state, which increased after detoxication (from 1.5+/-0.4 to 5.6+/-1.2; p<0.01). It is concluded that alcohol abuse lowers the hepatic production of IGF-I and increases the production of IGFBP-1. This results in a reduced IGF-I bioavailability. However, in patients with not yet clinically apparent liver damage the IGF-I bioavailability increases if the alcohol abuse is stopped. These findings could reflect an important

  4. Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol.

    PubMed

    Morais-Silva, G; Fernandes-Santos, J; Moreira-Silva, D; Marin, M T

    2016-01-01

    Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30-35 g, 8-10 per group) were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a "three-bottle choice" paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

  5. Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure.

    PubMed

    Barbier, Estelle; Pierrefiche, Olivier; Vaudry, David; Vaudry, Hubert; Daoust, Martine; Naassila, Mickaël

    2008-12-01

    Exposure to ethanol early in life can have long-lasting implications on brain function and drug of abuse response later in life. The present study investigated in rats, the long-term consequences of pre- and postnatal (early life) ethanol exposure on drug consumption/reward and the molecular targets potentially associated with these behavioral alterations. Since a relationship has been demonstrated between heightened drugs intake and susceptibility to drugs-induced locomotor activity/sensitization, anxiolysis, we tested these behavioral responses, depending on the drug, in control and early life ethanol-exposed animals. Our results show that progeny exposed to early life ethanol displayed increased consumption of ethanol solutions and increased sensitivity to cocaine rewarding effects assessed in the conditioned place preference test. Offspring exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and the increased sensitivity could, at least in part, explain the alteration in the consumption of ethanol for its anxiolytic effects. In addition, the sensitivity to hypothermic effects of ethanol and ethanol metabolism were not altered by early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and, could partly explain, an increase in the rewarding properties of psychostimulants. Gene expression analysis revealed that expression of a large number of genes was altered in brain regions involved in the reinforcing effects of drugs of abuse. Dopaminergic receptors and transporter binding sites were also down-regulated in the striatum of ethanol-exposed offspring. Such long-term neurochemical alterations in transmitter systems and in the behavioral responses to ethanol and other drugs of abuse may confer an increased liability for addiction in exposed offspring.

  6. Using in vitro models for expression profiling studies on ethanol and drugs of abuse.

    PubMed

    Thibault, Christelle; Hassan, Sajida; Miles, Michael

    2005-03-01

    The use of expression profiling with microarrays offers great potential for studying the mechanisms of action of drugs of abuse. Studies with the intact nervous system seem likely to be most relevant to understanding the mechanisms of drug abuse-related behaviours. However, the use of expression profiling with in vitro culture models offers significant advantages for identifying details of cellular signalling actions and toxicity for drugs of abuse. This study discusses general issues of the use of microarrays and cell culture models for studies on drugs of abuse. Specific results from existing studies are also discussed, providing clear examples of relevance for in vitro studies on ethanol, nicotine, opiates, cannabinoids and hallucinogens such as LSD. In addition to providing details on signalling mechanisms relevant to the neurobiology of drugs of abuse, microarray studies on a variety of cell culture systems have also provided important information on mechanisms of cellular/organ toxicity with drugs of abuse. Efforts to integrate genomic studies on drugs of abuse with both in vivo and in vitro models offer the potential for novel mechanistic rigor and physiological relevance.

  7. Food deprivation increases the low-dose locomotor stimulant response to ethanol in Drosophila melanogaster.

    PubMed

    Kliethermes, Christopher L

    2013-10-01

    Acute and chronic states of food deprivation result in increased sensitivity to a variety of natural reinforcers as well as to drugs of abuse. Food deprived animals show increased locomotor activity during periods of food deprivation, as well as increased locomotor stimulant responses to drugs of abuse, including cocaine, amphetamine, morphine, and ethanol, implying that drugs of abuse act in part on neural systems that underlie responses towards food. To determine whether this effect extends to an invertebrate, highly genetically tractable animal, the locomotor stimulant effects of low dose ethanol were assessed under a variety of feeding conditions in the fruit fly, Drosophila melanogaster. Food deprivation resulted in strain specific increases in ethanol-stimulated locomotor activity in most strains tested, although elevated baseline activity confounded interpretation in some strains. Experiments conducted with Canton S flies found that the effects of food deprivation on the locomotor stimulant response to ethanol increased with the duration of deprivation, and could be blocked by refeeding the flies with standard food or sucrose, but not yeast, immediately prior to the ethanol exposure. Life-span extending dietary depletion procedures or previous periods of food deprivation did not affect the response to ethanol, indicating that only animals in an acutely food deprived state are more sensitive to the stimulant effects of ethanol. These results suggest that increased sensitivity to the stimulant effects of some drugs of abuse might reflect an evolutionarily conserved neural mechanism that underlies behavioral responses to natural reinforcers and drugs of abuse. The identification of this mechanism, and the genes that underlie its development and function, will constitute a novel approach towards the study of alcohol abuse and dependence. © 2013.

  8. The effects of continuous and intermittent ethanol exposure in adolesence on the aversive properties of ethanol during adulthood.

    PubMed

    Diaz-Granados, Jaime L; Graham, Danielle L

    2007-12-01

    Alcohol abuse among adolescents is prevalent. Epidemiological studies suggest that alcohol abuse during the adolescent developmental period may result in long-term changes such as an increased susceptibility to alcohol-related problems in adulthood. Laboratory findings suggest that alcohol exposure during the adolescent developmental period, as compared with adulthood, may differentially impact subsequent neurobehavioral responses to alcohol. The present study was designed to examine whether ethanol exposure, continuous versus intermittent, during the adolescent developmental period would alter the aversive properties of ethanol in adult C3H mice. Periadolescent (PD28) male C3H mice were exposed to 64 hours of continuous or intermittent ethanol vapor. As a comparison, adult (PD70) C3H mice were also exposed to 64 hours of continuous or intermittent ethanol vapor. Six weeks after ethanol exposure, taste aversion conditioning was carried out on both ethanol pre-exposed and ethanol-naive animals using a 1-trial, 1-flavor taste-conditioning procedure. Ethanol exposure during the periadolescent period significantly attenuated a subsequent ethanol-induced conditioned taste aversion, as compared with control animals. Adult animals exposed to chronic ethanol vapor during adolescence showed less of an aversion to an ethanol-paired flavor than ethanol-naive adults. Intermittent exposure to ethanol vapor during periadolescence produced a greater attenuation. It is suggested that ethanol exposure during the periadolescent period results in long-term neurobehavioral changes, which lessen a conditioned aversion to ethanol in adulthood. It is suggested that this age-related effect may underlie the increased susceptibility to alcohol-related problems which is negatively correlated with the age of onset for alcohol abuse.

  9. Time-Course of the Ethanol-like Discriminative Stimulus Effects of Abused Inhalants in Mice

    PubMed Central

    Bowen, Scott E.

    2009-01-01

    Abused solvents have effects similar to those of abused depressant drugs. This experiment evaluated the time course of the discriminative stimulus effects of toluene and 1,1,1-trichloroethane (TRI). Mice were trained to discriminate between i.p. injections of ethanol (EtOH;1.25 g/kg) and saline in a two-lever operant task in which responding was under the control of a fixed-ratio 20 schedule. After 20-min inhalation exposures to toluene (500–6000 ppm) or TRI (1,000–12,000 ppm), stimulus generalization was examined at 0, 5, 10, 20, and 40 min post-exposure. Ethanol doses ≥ 0.25 g/kg produced increases in EtOH-lever responding with full substitution occurring immediately after testing for doses between 1.25 and 2.5 g/kg. Toluene and TRI produced increased EtOH-lever responding at 0–10 min post exposure with some EtOH-lever responding occurring up to 20-min post exposure. Response rates were not decreased for any concentration of toluene or TRI immediately following inhalant exposure but several concentrations elevated rates from 5–40 min post exposure. These results confirm and extend previous studies and show these solvents produce similar effects in EtOH-lever responding but with potency differences. The time-dependent differences in EtOH-lever responding suggest that as solvents are cleared from the body, the EtOH-like subjective effects also fade. PMID:18722399

  10. Lesions of the Lateral Habenula Increase Voluntary Ethanol Consumption and Operant Self-Administration, Block Yohimbine-Induced Reinstatement of Ethanol Seeking, and Attenuate Ethanol-Induced Conditioned Taste Aversion

    PubMed Central

    Schwager, Andrea L.; Sinclair, Michael S.; Tandon, Shashank; Taha, Sharif A.

    2014-01-01

    The lateral habenula (LHb) plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug. PMID:24695107

  11. Lesions of the lateral habenula increase voluntary ethanol consumption and operant self-administration, block yohimbine-induced reinstatement of ethanol seeking, and attenuate ethanol-induced conditioned taste aversion.

    PubMed

    Haack, Andrew K; Sheth, Chandni; Schwager, Andrea L; Sinclair, Michael S; Tandon, Shashank; Taha, Sharif A

    2014-01-01

    The lateral habenula (LHb) plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug.

  12. Characteristics of ethanol-induced behavioral sensitization in rats: Molecular mediators and cross-sensitization between ethanol and cocaine.

    PubMed

    Xu, Shijie; Kang, Ung Gu

    2017-09-01

    Repeated exposure to drugs of abuse can induce a progressive increase in locomotor activity, known as behavioral sensitization. However, little is known about behavioral sensitization to ethanol. We examined whether ethanol could induce behavioral sensitization and investigated several molecular changes accompanying sensitization. We also assessed whether "cross-sensitization" occurred between ethanol and cocaine, another abused drug. Ethanol-induced sensitization was examined in rats after ethanol treatment (0.5 or 2g/kg) for 15days. The biochemical effects of low- or high-dose ethanol were examined in terms of N-methyl-d-aspartate (NMDA) receptor subunit phosphorylation or expression. Neuronal activity after ethanol treatment was assessed by measuring the level of early growth response (Egr-1) expression. Ethanol-induced behavioral sensitization was observed at the low dose (0.5g/kg) but not the high dose (2g/kg). Although acute treatment with the sensitizing dose of ethanol robustly increased Egr-1 protein and mRNA levels, the expression and phosphorylation of NMDA receptor subunits were not affected. The biochemical responses to ethanol seemed to be enhanced in ethanol-sensitized animals. Cross-sensitization between ethanol and cocaine was observed, which supports the hypothesis that there are commonalities among substances in the pathophysiology of substance dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Vitamin B6 metabolism in chronic alcohol abuse The effect of ethanol oxidation on hepatic pyridoxal 5'-phosphate metabolism.

    PubMed Central

    Vech, R L; Lumeng, L; Li, T K

    1975-01-01

    Individuals with chronic alcohol abuse frequently exhibit lowered plasma levels of pyridoxal 5'-phosphate, the coenzyme form of vitamin B6. Because the liver is the primary source of this coenzyme in plasma and also the principal organ that oxidizes ethanol, the effect of ethanol on hepatic pyridoxal phosphate metabolism was studied in the rat. The chronic feeding of ethanol (36 percent of the total dietary calories) for 6 wk significantly decreased the hepatic pyridoxal phosphate content both in animals given a sufficient amount of vitamin B6 in their diet and in those rendered vitamin B6 deficient. In isolated perfused livers, the addition of 18 mM ethanol lowered the pyridoxal phosphate content of livers from vitamin B6-sufficient animals and deceased the net synthesis of pyridoxal phosphate from pyridoxine by the livers of vitamin B6-deficient animals. Ethanol also diminished the rate of release of pyridoxal phosphate into the perfusate by the livers of vitamin B6-deficient rats. These effects of ethanol, in vitro, were abolished by 4-methyl pyrazole, an inhibitor of alcohol dehydrogenase. Thus the derangement of pyridoxal phosphate metabolism produced by ethanol is dependt upon its oxidation. These data support previous findings whic indicate that acetaldehyde is the responsible agent which acts by accelerating the degradation of intracellular pyridoxal phosphate. Images PMID:1168205

  14. Ethanol Administration Impairs Pancreatic Repair Following Injury

    PubMed Central

    Mahan Schneider, Katrina J.; Scheer, Marc; Suhr, Mallory; Clemens, Dahn L.

    2012-01-01

    Objectives Alcohol abuse is one of the most common factors associated with acute and chronic pancreatitis. Although it is evident that alcohol abuse can have an important role in the development of pancreatitis, it does not appear that alcohol abuse alone is responsible for this disease. We investigated the involvement of ethanol in impairment of pancreatic repair after induction of pancreatitis. Methods A biologically relevant mouse model of alcoholic pancreatitis, combining chronic ethanol consumption and coxsackievirus infection, was used to investigate the effects of ethanol on pancreatic regeneration. Tissues were harvested and analyzed by RT-PCR and immunoblot. Results These studies demonstrate that chronic ethanol consumption impairs the structural repair of the exocrine pancreas. This is accompanied by a delay in the restitution of lipase expression. Additionally, impaired expression of the critical pancreatic transcription factors, PDX1 and PTF1, and the mediator of Notch signaling, HES1, were observed. Conclusions Chronic ethanol consumption impairs the structural repair and functional restitution of the pancreas after severe injury. These impairments may, in part, be explained by impaired expression of factors important in the development and maintenance of the exocrine pancreas. Impaired pancreatic regeneration may have a role in the pathogenesis of alcoholic pancreatitis. PMID:22617711

  15. Accentuating effects of nicotine on ethanol response in mice with high genetic predisposition to ethanol-induced locomotor stimulation.

    PubMed

    Gubner, N R; McKinnon, C S; Reed, C; Phillips, T J

    2013-01-01

    Co-morbid use of nicotine-containing tobacco products and alcohol is prevalent in alcohol dependent individuals. Common genetic factors could influence initial sensitivity to the independent or interactive effects of these drugs and play a role in their co-abuse. Locomotor sensitivity to nicotine and ethanol, alone and in combination, was assessed in mice bred for high (FAST) and low (SLOW) sensitivity to the locomotor stimulant effects of ethanol and in an inbred strain of mouse (DBA/2J) that has been shown to have extreme sensitivity to ethanol-induced stimulation in comparison to other strains. The effects of nicotine and ethanol, alone and in combination, were dependent on genotype. In FAST and DBA/2J mice that show high sensitivity to ethanol-induced stimulation, nicotine accentuated the locomotor stimulant response to ethanol. This effect was not found in SLOW mice that are not stimulated by ethanol alone. These data indicate that genes underlying differential sensitivity to the stimulant effects of ethanol alone also influence sensitivity to nicotine in combination with ethanol. Sensitivity to the stimulant effects of nicotine alone does not appear to predict the response to the drug combination, as FAST mice are sensitive to nicotine-induced stimulation, whereas SLOW and DBA/2J mice are not. The combination of nicotine and ethanol may have genotype-dependent effects that could impact co-abuse liability. Published by Elsevier Ireland Ltd.

  16. Ethylphenidate as a selective dopaminergic agonist and methylphenidate-ethanol transesterification biomarker

    PubMed Central

    Patrick, Kennerly S.; Corbin, Timothy R.; Murphy, Cristina E.

    2014-01-01

    We review the pharmaceutical science of ethylphenidate (EPH) in the contexts of drug discovery; drug interactions; biomarker for dl-methylphenidate (MPH)-ethanol exposure; potentiation of dl-MPH abuse liability; contemporary “designer drug”; pertinence to the newer transdermal and chiral switch MPH formulations; as well as problematic internal standard. d-EPH selectively targets the dopamine transporter while d-MPH exhibits equipotent actions at dopamine and norepinephrine transporters. This selectivity carries implications for the advancement of tailored attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in the era of genome-based diagnostics. Abuse of dl-MPH often involves ethanol co-abuse. Carboxylesterase 1 enantioselectively transesterifies l-MPH with ethanol to yield l-EPH accompanied by significantly increased early exposure to d-MPH and rapid potentiation of euphoria. The pharmacokinetic component of this drug interaction can largely be avoided using dexmethylphenidate (dexMPH). This notwithstanding, maximal potentiated euphoria occurs following dexMPH-ethanol. C57BL/6 mice model dl-MPH-ethanol interactions: An otherwise depressive dose of ethanol synergistically increases dl-MPH stimulation; A sub-stimulatory dose of dl-MPH potentiates a low, stimulatory dose of ethanol; Ethanol elevates blood, brain and urinary d-MPH concentrations while forming l-EPH. Integration of EPH preclinical neuropharmacology with clinical studies of MPH-ethanol interactions provides a translational approach toward advancement of ADHD personalized medicine and management of comorbid alcohol use disorder. PMID:25303048

  17. Interaction of biogenic amines with ethanol.

    PubMed

    Smith, A A

    1975-01-01

    Ethanol through its primary catabolite, acetaldehyde, competitively inhibits oxidation of aldehyde dehydrogenase substrates. As a consequence biogenic amines form increased quantities of alcohols rather than the corresponding acids. During this biotransformation, condensation reactions between deaminated and intact amines may occur which can yield tetrahydropapaverolines. These compounds are closely related to precursors of opioids which is cause to link ethanol abuse to morphine addiction. There is, however, no pharmacological or clinical evidence suggesting similarities between ethanol dependence or opiod addiction. Acetaldehyde plays an additional role in alkaloidal formation in vitro. Biogenic amines may react with acetaldehyde to form isoquinoline or carboline compounds. Some of these substances have significant pharmacological activity. Furthermore, they may enter neural stores and displace the natural neurotransmitter. Thus, they can act as false neurotransmitters. Some investigators believe that chronic ethanol ingestion leads to significant formation of such aberrant compounds which may then upset autonomic nervous system balance. This disturbance may explain the abnormal sympathetic activity seen in withdrawal. While these ideas about the etiology of alcohol abuse have a definite appeal, they are naturally based on in vitro preliminary work. Much study of the quantitative pharmacology of these compounds in animals is required before judgement can be made as to the merits of the proposed hypotheses. In the meantime, pharmacological studies on the ability of ethanol to depress respiration in the mouse has revealed that unlike opioids or barbituates, respiratory depression induced by ethanol requires the presence in brain of serotonin. This neurotransmitter also mediates the respiratory effects of several other alcohols but curiously, not chloral hydrate, yet this compound is purported to alter biogenic amine metabolism much like ethanol. Thus, the response

  18. ACUTE ETHANOL MODULATES GLUTAMATERGIC AND SEROTONERGIC PHASE SHIFTS OF THE MOUSE CIRCADIAN LOCK IN VITRO

    PubMed Central

    Prosser, Rebecca A.; Mangrum, Charles A.; Glass, J. David

    2008-01-01

    Alcohol abuse is associated with sleep problems, which are often linked to circadian rhythm disturbances. However, there is no information on the direct effects of ethanol on the mammalian circadian clock. Acute ethanol inhibits glutamate signaling, which is the primary mechanism through which light resets the mammalian clock in the suprachiasmatic nucleus (SCN). Glutamate and light also inhibit circadian clock resetting induced by non-photic signals, including serotonin. Thus, we investigated the effects of acute ethanol on both glutamatergic and serotoninergic resetting of the SCN clock in vitro. We show that ethanol dose-dependently inhibits glutamate-induced phase shifts and enhances serotonergic phase shifts. The inhibition of glutamate-induced phase shifts is not affected by excess glutamate, glycine or D-serine, but is prevented by excess brain-derived neurotrophic factor (BDNF). BDNF is known to augment glutamate signaling in the SCN and to be necessary for glutamate/light-induced phase shifts. Thus, ethanol may inhibit glutamate-induced clock resetting at least in part by blocking BDNF enhancement of glutamate signaling. Ethanol enhancement of serotonergic phase shifts is mimicked by treatments that suppress glutamate signaling in the SCN, including antagonists of glutamate receptors, BDNF signaling and nitric oxide synthase. The combined effect of ethanol with these treatments is not additive, suggesting they act through a common pathway. Our data indicate further that the interaction between serotonin and glutamate in the SCN may occur downstream from nitric oxide synthase activation. Thus, acute ethanol disrupts normal circadian clock phase regulation, which could contribute to the physiological and psychological problems associated with alcohol abuse. PMID:18313227

  19. Conditioned effects of ethanol on the immune system.

    PubMed

    Gano, Anny; Pautassi, Ricardo Marcos; Doremus-Fitzwater, Tamara L; Deak, Terrence

    2017-04-01

    Several studies indicate that the immune system can be subjected to classical conditioning. Acute ethanol intoxication significantly modulates several pro-inflammatory cytokines (e.g. interleukins-1 and 6 [IL-1β and IL-6, respectively] and tumor necrosis factor alpha [TNFα])) in several brain areas, including amygdala (AMG), paraventricular nucleus (PVN), and hippocampus (HPC). It is unknown, however, whether cues associated with ethanol can elicit conditioned alterations in cytokine expression. The present study analyzed, in male Sprague-Dawley rats, whether ethanol-induced changes in the central cytokine response may be amenable to conditioning. In Experiments 1 and 2, the rats were given one or two pairings between a distinctive odor (conditional stimulus, CS) and the post-absorptive effects of a high (3.0 or 4.0 g/kg, Experiments 1 and 2, respectively) ethanol dose. Neither of these experiments revealed conditioning of IL-6, IL-1β, or TNFα, as measured via mRNA levels. Yet, re-exposure to the lemon-odor CS in Experiment 1 significantly increased C-Fos levels in the PVN. In Experiment 3, the rats were given four pairings between an odor CS and a moderate ethanol dose (2.0 g/kg), delivered intraperitoneally (i.p.) or intragastrically (i.g.). Re-exposure to the odor CS significantly increased IL-6 levels in HPC and AMG, an effect only evident in paired rats administered ethanol i.p. Overall, this study suggests that ethanol exposure can regulate the levels of IL-6 at HPC and AMG via classical conditioning mechanisms. These ethanol-induced, conditioned alterations in cytokine levels may ultimately affect the intake and motivational effects of ethanol. Impact statement This study examines, across three experiments, whether odor cues associated with ethanol exposure can condition changes in cytokine expression. The analysis of ethanol-induced conditioning of immune responses is a novel niche that can help understand the transition from social drinking to

  20. Fetal ethanol exposure increases ethanol intake by making it smell and taste better

    PubMed Central

    Youngentob, Steven L.; Glendinning, John I.

    2009-01-01

    Human epidemiologic studies reveal that fetal ethanol exposure is highly predictive of adolescent ethanol avidity and abuse. Little is known about how fetal exposure produces these effects. It is hypothesized that fetal ethanol exposure results in stimulus-induced chemosensory plasticity. Here, we asked whether gestational ethanol exposure increases postnatal ethanol avidity in rats by altering its taste and odor. Experimental rats were exposed to ethanol in utero via the dam's diet, whereas control rats were either pair-fed an iso-caloric diet or given food ad libitum. We found that fetal ethanol exposure increased the taste-mediated acceptability of both ethanol and quinine hydrochloride (bitter), but not sucrose (sweet). Importantly, a significant proportion of the increased ethanol acceptability could be attributed directly to the attenuated aversion to ethanol's quinine-like taste quality. Fetal ethanol exposure also enhanced ethanol intake and the behavioral response to ethanol odor. Notably, the elevated intake of ethanol was also causally linked to the enhanced odor response. Our results demonstrate that fetal exposure specifically increases ethanol avidity by, in part, making it taste and smell better. More generally, they establish an epigenetic chemosensory mechanism by which maternal patterns of drug use can be transferred to offspring. Given that many licit (e.g., tobacco products) and illicit (e.g., marijuana) drugs have noteworthy chemosensory components, our findings have broad implications for the relationship between maternal patterns of drug use, child development, and postnatal vulnerability. PMID:19273846

  1. Fetal ethanol exposure increases ethanol intake by making it smell and taste better.

    PubMed

    Youngentob, Steven L; Glendinning, John I

    2009-03-31

    Human epidemiologic studies reveal that fetal ethanol exposure is highly predictive of adolescent ethanol avidity and abuse. Little is known about how fetal exposure produces these effects. It is hypothesized that fetal ethanol exposure results in stimulus-induced chemosensory plasticity. Here, we asked whether gestational ethanol exposure increases postnatal ethanol avidity in rats by altering its taste and odor. Experimental rats were exposed to ethanol in utero via the dam's diet, whereas control rats were either pair-fed an iso-caloric diet or given food ad libitum. We found that fetal ethanol exposure increased the taste-mediated acceptability of both ethanol and quinine hydrochloride (bitter), but not sucrose (sweet). Importantly, a significant proportion of the increased ethanol acceptability could be attributed directly to the attenuated aversion to ethanol's quinine-like taste quality. Fetal ethanol exposure also enhanced ethanol intake and the behavioral response to ethanol odor. Notably, the elevated intake of ethanol was also causally linked to the enhanced odor response. Our results demonstrate that fetal exposure specifically increases ethanol avidity by, in part, making it taste and smell better. More generally, they establish an epigenetic chemosensory mechanism by which maternal patterns of drug use can be transferred to offspring. Given that many licit (e.g., tobacco products) and illicit (e.g., marijuana) drugs have noteworthy chemosensory components, our findings have broad implications for the relationship between maternal patterns of drug use, child development, and postnatal vulnerability.

  2. 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

  3. Oral and transdermal DL-methylphenidate-ethanol interactions in C57BL/6J mice: potentiation of locomotor activity with oral delivery.

    PubMed

    Bell, Guinevere H; Griffin, William C; Patrick, Kennerly S

    2011-12-01

    Many abusers of dl-methylphenidate co-abuse ethanol. The present animal study examined behavioral effects of oral or transdermal DL-methylphenidate in combination with a high, depressive dose of ethanol to model co-abuse. Locomotor activity of C57BL/6J mice was recorded for 3 h following dosing with either oral DL-methylphenidate (7.5 mg/kg) or transdermal DL-methylphenidate (Daytrana®;1/4 of a 12.5 cm(2) patch; mean dose 7.5 mg/kg), with or without oral ethanol (3 g/kg). Brains were enantiospecifically analyzed for the isomers of methylphenidate and the transesterification metabolite ethylphenidate. An otherwise depressive dose of ethanol significantly potentiated oral DL-methylphenidate induced increases in total distance traveled for the first 100 min (p<0.05). Transdermal DL-methylphenidate increased total distance traveled after a latency of 80 min, though this effect was not potentiated by concomitant ethanol. Mean 3 h brain D-methylphenidate concentrations were significantly elevated by ethanol in both the oral (65% increase) and transdermal (88% increase) groups. The corresponding L-ethylphenidate concentrations were 10 ng/g and 130 ng/g. Stimulant induced motor activity in rodents may correlate with abuse liability. Potentiation of DL-methylphenidate motor effects by concomitant ethanol carries implications regarding increased abuse potential of DL-methylphenidate when combined with ethanol. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Conditioned effects of ethanol on the immune system

    PubMed Central

    Gano, Anny; Doremus-Fitzwater, Tamara L; Deak, Terrence

    2017-01-01

    Several studies indicate that the immune system can be subjected to classical conditioning. Acute ethanol intoxication significantly modulates several pro-inflammatory cytokines (e.g. interleukins-1 and 6 [IL-1β and IL-6, respectively] and tumor necrosis factor alpha [TNFα])) in several brain areas, including amygdala (AMG), paraventricular nucleus (PVN), and hippocampus (HPC). It is unknown, however, whether cues associated with ethanol can elicit conditioned alterations in cytokine expression. The present study analyzed, in male Sprague-Dawley rats, whether ethanol-induced changes in the central cytokine response may be amenable to conditioning. In Experiments 1 and 2, the rats were given one or two pairings between a distinctive odor (conditional stimulus, CS) and the post-absorptive effects of a high (3.0 or 4.0 g/kg, Experiments 1 and 2, respectively) ethanol dose. Neither of these experiments revealed conditioning of IL-6, IL-1β, or TNFα, as measured via mRNA levels. Yet, re-exposure to the lemon-odor CS in Experiment 1 significantly increased C-Fos levels in the PVN. In Experiment 3, the rats were given four pairings between an odor CS and a moderate ethanol dose (2.0 g/kg), delivered intraperitoneally (i.p.) or intragastrically (i.g.). Re-exposure to the odor CS significantly increased IL-6 levels in HPC and AMG, an effect only evident in paired rats administered ethanol i.p. Overall, this study suggests that ethanol exposure can regulate the levels of IL-6 at HPC and AMG via classical conditioning mechanisms. These ethanol-induced, conditioned alterations in cytokine levels may ultimately affect the intake and motivational effects of ethanol. Impact statement This study examines, across three experiments, whether odor cues associated with ethanol exposure can condition changes in cytokine expression. The analysis of ethanol-induced conditioning of immune responses is a novel niche that can help understand the transition from social drinking to

  5. Common genes regulate food and ethanol intake in Drosophila.

    PubMed

    Sekhon, Morgan L; Lamina, Omoteniola; Hogan, Kerry E; Kliethermes, Christopher L

    2016-06-01

    The abuse liability of alcohol (ethanol) is believed to result in part from its actions on neurobiological substrates that underlie the motivation toward food and other natural reinforcers, and a growing body of evidence indicates that these substrates are broadly conserved among animal phyla. Understanding the extent to which the substrates regulating ethanol and food intake overlap is an important step toward developing therapeutics that selectively reduce ethanol intake. In the current experiments, we measured food and ethanol intake in Recombinant Inbred (RI) lines of Drosophila melanogaster using several assays, and then calculated genetic correlations to estimate the degree to which common genes might underlie behavior in these assays. We found that food intake and ethanol intake as measured in the capillary assay are genetically correlated traits in D. melanogaster, as well as in a panel of 11 Drosophila species that we tested subsequently. RI line differences in food intake in a dyed food assay were genetically unrelated to ethanol intake in the capillary assay or to ethanol preference measured using an olfactory trap apparatus. Using publicly available gene expression data, we found that expression profiles across the RI lines of a number of genes (including the D2-like dopamine receptor, DOPA decarboxylase, and fruitless) correlated with the RI line differences in food and ethanol intake we measured, while the expression profiles of other genes, including NPF, and the NPF and 5-HT2 receptors, correlated only with ethanol intake or preference. Our results suggest that food and ethanol intake are regulated by some common genes in Drosophila, but that other genes regulate ethanol intake independently of food intake. These results have implications toward the development of therapeutics that preferentially reduce ethanol intake. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. 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

  7. 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.

  8. Aversive effects of ethanol in adolescent versus adult rats: potential causes and implication for future drinking.

    PubMed

    Schramm-Sapyta, Nicole L; DiFeliceantonio, Alexandra G; Foscue, Ethan; Glowacz, Susan; Haseeb, Naadeyah; Wang, Nancy; Zhou, Cathy; Kuhn, Cynthia M

    2010-12-01

    Many people experiment with alcohol and other drugs of abuse during their teenage years. Epidemiological evidence suggests that younger initiates into drug taking are more likely to develop problematic drug seeking behavior, including binge and other high-intake behaviors. The level of drug intake for any individual depends on the balance of rewarding and aversive effects of the drug in that individual. Multiple rodent studies have demonstrated that aversive effects of drugs of abuse are reduced in adolescent compared to adult animals. In this study, we addressed 2 key questions: First, do reduced aversive effects of ethanol in younger rats correlate with increased ethanol consumption? Second, are the reduced aversive effects in adolescents attributable to reduced sensitivity to ethanol's physiologic effects? Adolescent and adult rats were tested for ethanol conditioned taste aversion (CTA) followed by a voluntary drinking period, including postdeprivation consumption. Multivariate regression was used to assess correlations. In separate experiments, adolescent and adult rats were tested for their sensitivity to the hypothermic and sedative effects of ethanol, and for blood ethanol concentrations (BECs). We observed that in adolescent rats but not adults, taste aversion was inversely correlated with postdeprivation consumption. Adolescents also exhibited a greater increase in consumption after deprivation than adults. Furthermore, the age difference in ethanol CTA was not attributable to differences in hypothermia, sedation, or BECs. These results suggest that during adolescence, individuals that are insensitive to aversive effects are most likely to develop problem drinking behaviors. These results underscore the importance of the interaction between developmental stage and individual variation in sensitivity to alcohol. Copyright © 2010 by the Research Society on Alcoholism.

  9. 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

  10. Rsu1 regulates ethanol consumption in Drosophila and humans.

    PubMed

    Ojelade, Shamsideen A; Jia, Tianye; Rodan, Aylin R; Chenyang, Tao; Kadrmas, Julie L; Cattrell, Anna; Ruggeri, Barbara; Charoen, Pimphen; Lemaitre, Hervé; Banaschewski, Tobias; Büchel, Christian; Bokde, Arun L W; Carvalho, Fabiana; Conrod, Patricia J; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny A; Heinz, Andreas; Ittermann, Bernd; Lathrop, Mark; Lubbe, Steven; Martinot, Jean-Luc; Paus, Tomás; Smolka, Michael N; Spanagel, Rainer; O'Reilly, Paul F; Laitinen, Jaana; Veijola, Juha M; Feng, Jianfeng; Desrivières, Sylvane; Jarvelin, Marjo-Riitta; Schumann, Gunter; Rothenfluh, Adrian

    2015-07-28

    Alcohol abuse is highly prevalent, but little is understood about the molecular causes. Here, we report that Ras suppressor 1 (Rsu1) affects ethanol consumption in flies and humans. Drosophila lacking Rsu1 show reduced sensitivity to ethanol-induced sedation. We show that Rsu1 is required in the adult nervous system for normal sensitivity and that it acts downstream of the integrin cell adhesion molecule and upstream of the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase to regulate the actin cytoskeleton. In an ethanol preference assay, global loss of Rsu1 causes high naïve preference. In contrast, flies lacking Rsu1 only in the mushroom bodies of the brain show normal naïve preference but then fail to acquire ethanol preference like normal flies. Rsu1 is, thus, required in distinct neurons to modulate naïve and acquired ethanol preference. In humans, we find that polymorphisms in RSU1 are associated with brain activation in the ventral striatum during reward anticipation in adolescents and alcohol consumption in both adolescents and adults. Together, these data suggest a conserved role for integrin/Rsu1/Rac1/actin signaling in modulating reward-related phenotypes, including ethanol consumption, across phyla.

  11. Ethylphenidate as a selective dopaminergic agonist and methylphenidate-ethanol transesterification biomarker.

    PubMed

    Patrick, Kennerly S; Corbin, Timothy R; Murphy, Cristina E

    2014-12-01

    We review the pharmaceutical science of ethylphenidate (EPH) in the contexts of drug discovery, drug interactions, biomarker for dl-methylphenidate (MPH)-ethanol exposure, potentiation of dl-MPH abuse liability, contemporary "designer drug," pertinence to the newer transdermal and chiral switch MPH formulations, as well as problematic internal standard. d-EPH selectively targets the dopamine transporter, whereas d-MPH exhibits equipotent actions at dopamine and norepinephrine transporters. This selectivity carries implications for the advancement of tailored attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in the era of genome-based diagnostics. Abuse of dl-MPH often involves ethanol coabuse. Carboxylesterase 1 enantioselectively transesterifies l-MPH with ethanol to yield l-EPH accompanied by significantly increased early exposure to d-MPH and rapid potentiation of euphoria. The pharmacokinetic component of this drug interaction can largely be avoided using dexmethylphenidate (dexMPH). This notwithstanding, maximal potentiated euphoria occurs following dexMPH-ethanol. C57BL/6 mice model dl-MPH-ethanol interactions: an otherwise depressive dose of ethanol synergistically increases dl-MPH stimulation; a substimulatory dose of dl-MPH potentiates a low, stimulatory dose of ethanol; ethanol elevates blood, brain, and urinary d-MPH concentrations while forming l-EPH. Integration of EPH preclinical neuropharmacology with clinical studies of MPH-ethanol interactions provides a translational approach toward advancement of ADHD personalized medicine and management of comorbid alcohol use disorder. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  12. Environmental enrichment reduces the impact of novelty and motivational properties of ethanol in spontaneously hypertensive rats.

    PubMed

    de Carvalho, Cristiane Ribeiro; Pandolfo, Pablo; Pamplona, Fabrício Alano; Takahashi, Reinaldo Naoto

    2010-03-17

    The present study investigated the consequences of environmental enrichment on the impact of novelty and motivational properties of ethanol in spontaneously hypertensive rats (SHR), a validated model of attention deficit hyperactivity disorder (ADHD). This rat strain displays increased sensitivity to distinct classes of abused drugs, which makes it an interesting model for the study of the association between ADHD and drug abuse. Female SHR reared from weaning to adulthood in standard (SE) or enriched (EE) environment were tested on novelty-induced locomotion, saccharin consumption, ethanol consumption (forced and free-choice schedules) and ethanol-induced conditioned place preference (CPP). SHR reared in an EE showed reduced novelty-induced locomotion, consumed less saccharin and ethanol in a forced schedule and showed less ethanol preference in a free-choice schedule compared to SE rats. Moreover, EE rats did not develop CPP, whereas SE rats developed preference for ethanol (1.2g/kg). These results show that exposure to stimuli mimicking positive life experiences (environmental enrichment) induces persistent changes in the reward/motivational system of female SHR, suggesting an important role of the familiar environment during early stages of the neurodevelopment on the co-morbidity of ADHD and drug abuse. Copyright 2009 Elsevier B.V. All rights reserved.

  13. Ethanol-BDNF interactions: Still More Questions than Answers

    PubMed Central

    Davis, Margaret I.

    2008-01-01

    Brain Derived Neurotrophic Factor (BDNF) has emerged as a regulator of development, plasticity and, recently, addiction. Decreased neurotrophic activity may be involved in ethanol-induced neurodegeneration in the adult brain and in the etiology of alcohol-related neurodevelopmental disorders. This can occur through decreased expression of BDNF or through inability of the receptor to transduce signals in the presence of ethanol. In contrast, recent studies implicate region-specific up-regulation of BDNF and associated signaling pathways in anxiety, addiction and homeostasis after ethanol exposure. Anxiety and depression are precipitating factors for substance abuse and these disorders also involve region-specific changes in BDNF in both pathogenesis and response to pharmacotherapy. Polymorphisms in the genes coding for BDNF and its receptor TrkB are linked to affective, substance abuse and appetitive disorders and therefore may play a role in the development of alcoholism. This review summarizes historical and pre-clinical data on BDNF and TrkB as it relates to ethanol toxicity and addiction. Many unresolved questions about region-specific changes in BDNF expression and the precise role of BDNF in neuropsychiatric disorders and addiction remain to be elucidated. Resolution of these questions will require significant integration of the literature on addiction and comorbid psychiatric disorders that contribute to the development of alcoholism. PMID:18394710

  14. A mouse model for chronic pain-induced increase in ethanol consumption.

    PubMed

    Butler, Ryan K; Knapp, Darin J; Ulici, Veronica; Longobardi, Lara; Loeser, Richard F; Breese, George R

    2017-03-01

    Chronic pain conditions are often comorbid with alcohol abuse. "Self-medication" with alcohol introduces a host of problems associated with the abuse of alcohol which over time has the potential of exacerbating the painful condition. Despite the prevalence of chronic pain being associated with alcohol abuse, rodent models which mimic the comorbid conditions are lacking. In this study, we model osteoarthritis (OA) in C57BL/6J mice by surgically destabilizing the medial meniscus (DMM). Sham-operated mice served as controls. Thirteen weeks after surgery, DMM but not sham-operated mice exhibited pronounced incapacitance of the surgically manipulated hind limb compared with the nonsurgically manipulated hind limb. At this time, the mice were exposed to the 2-bottle ethanol choice, beginning with 2.5% with a gradual increasing to 20%. Compared with sham controls, DMM mice consumed more EtOH and preferred EtOH over water at the 20% EtOH concentration. Histological analysis verified that the DMM mice exhibited significant damage to the articular cartilage and osteophyte growth compared with sham controls and these measures of the severity of OA correlated with the amount of ethanol intake. Thus, the combination of the DMM model of OA with the enhanced two-bottle ethanol choice is a potential preclinical approach in mice by which the basis of the comorbid association of alcohol abuse and chronic pain conditions can be explored.

  15. Abuse liability assessment of tobacco products including potential reduced exposure products.

    PubMed

    Carter, Lawrence P; Stitzer, Maxine L; Henningfield, Jack E; O'Connor, Rich J; Cummings, K Michael; Hatsukami, Dorothy K

    2009-12-01

    The harm produced by tobacco products is a result of frequent use of a highly toxic product. Reducing the adverse public health impact of tobacco products might be most effectively achieved by reducing the likelihood of their use and the toxicity of the products. Products that retain some characteristics of cigarettes but have been altered with the intention of reducing toxicity have been referred to as modified risk tobacco products or potential reduced exposure products (MRTP/PREP). Evaluation of their content, emission, and toxicity is discussed in other articles in this special issue. Here, we discuss the methodology that has been used to examine the likelihood of abuse or addiction. Abuse liability assessment (ALA) methodology has been used by the Food and Drug Administration (FDA) and other drug regulatory agencies world-wide for decades to assess the risks posed by a wide variety of pharmacologically active substances. ALA is routinely required among other evaluations of safety during the pre-market assessment of new drugs, and is continually adapted to meet the challenges posed by new drug classes and drug formulations. In the 2009 law giving FDA regulation over tobacco products, FDA is now required to evaluate new tobacco products including MRTP/PREPs to determine their risk for abuse and toxicity at the population level. This article describes the traditional tools and methods of ALA that can be used to evaluate new tobacco and nicotine products including MRTP/PREPs. Such ALA data could contribute to the scientific foundation on which future public policy decisions are based.

  16. [An integrated approach including paediatric and forensic medical expertise on suspicion of child abuse].

    PubMed

    Schouten, M C M; Karst, W A; van der Stel, H F; Teeuw, A H; van de Putte, E M

    2016-01-01

    A false accusation of child abuse has a major impact on child and family. Conversely, a missed diagnosis of child abuse may have significant and lifelong consequences for the child. For health professionals the assessment of the nature of the injury and differentiating between accidental and inflicted injury, disease manifestation or a physiological phenomenon can be challenging. For adequate determination of the cause of injury, an integrated approach including paediatric knowledge and forensic medical expertise is essential. Therefore, a national expertise centre for child abuse (LECK) was established in the Netherlands in 2014. The first results of this integrated approach are described and illustrated with three case reports. Case A, a 7-month-old boy with an accidental humerus fracture. Case B, an 8-year-old boy with a false positive suspicion of child abuse who was eventually diagnosed with Henoch-Schönlein syndrome. Case C, boy of 3 months with bruises and a metaphyseal fracture of the femur, both highly suspected of being inflicted injury.

  17. Acetaldehyde involvement in ethanol's postabsortive effects during early ontogeny.

    PubMed

    March, Samanta M; Abate, P; Molina, Juan C

    2013-01-01

    Clinical and biomedical studies sustains the notion that early ontogeny is a vulnerable window to the impact of alcohol. Experiences with the drug during these stages increase latter disposition to prefer, use or abuse ethanol. This period of enhanced sensitivity to ethanol is accompanied by a high rate of activity in the central catalase system, which metabolizes ethanol in the brain. Acetaldehyde (ACD), the first oxidation product of ethanol, has been found to share many neurobehavioral effects with the drug. Cumulative evidence supports this notion in models employing adults. Nevertheless very few studies have been conducted to analyze the role of ACD in ethanol postabsorptive effects, in newborns or infant rats. In this work we review recent experimental literature that syndicates ACD as a mediator agent of reinforcing aspects of ethanol, during early ontogenetic stages. We also show a meta-analytical correlational approach that proposes how differences in the activity of brain catalase across ontogeny, could be modulating patterns of ethanol consumption.

  18. Gestational naltrexone ameliorates fetal ethanol exposures enhancing effect on the postnatal behavioral and neural response to ethanol

    PubMed Central

    Youngentob, Steven L; Kent, Paul F; Youngentob, Lisa M

    2012-01-01

    The association between gestational exposure to ethanol and adolescent ethanol abuse is well established. Recent animal studies support the role of fetal ethanol experience-induced chemosensory plasticity as contributing to this observation. Previously, we established that fetal ethanol exposure, delivered through a dam’s diet throughout gestation, tuned the neural response of the peripheral olfactory system of early postnatal rats to the odor of ethanol. This occurred in conjunction with a loss of responsiveness to other odorants. The instinctive behavioral response to the odor of ethanol was also enhanced. Importantly, there was a significant contributory link between the altered response to the odor of ethanol and increased ethanol avidity when assessed in the same animals. Here, we tested whether the neural and behavioral olfactory plasticity, and their relationship to enhanced ethanol intake, is a result of the mere exposure to ethanol or whether it requires the animal to associate ethanol’s reinforcing properties with its odor attributes. In this later respect, the opioid system is important in the mediation (or modulation) of the reinforcing aspects of ethanol. To block endogenous opiates during prenatal life, pregnant rats received daily intraperitoneal administration of the opiate antagonist naltrexone from gestational day 6–21 jointly with ethanol delivered via diet. Relative to control progeny, we found that gestational exposure to naltrexone ameliorated the enhanced postnatal behavioral response to the odor of ethanol and postnatal drug avidity. Our findings support the proposition that in utero ethanol-induced olfactory plasticity (and its relationship to postnatal intake) requires, at least in part, the associative pairing between ethanol’s odor quality and its reinforcing aspects. We also found suggestive evidence that fetal naltrexone ameliorated the untoward effects of gestational ethanol exposure on the neural response to non

  19. Glycine and GABAA Ultra-Sensitive Ethanol Receptors as Novel Tools for Alcohol and Brain Research

    PubMed Central

    Naito, Anna; Muchhala, Karan H.; Asatryan, Liana; Trudell, James R.; Homanics, Gregg E.; Perkins, Daya I.; Alkana, Ronald L.

    2014-01-01

    A critical obstacle to developing effective medications to prevent and/or treat alcohol use disorders is the lack of specific knowledge regarding the plethora of molecular targets and mechanisms underlying alcohol (ethanol) action in the brain. To identify the role of individual receptor subunits in ethanol-induced behaviors, we developed a novel class of ultra-sensitive ethanol receptors (USERs) that allow activation of a single receptor subunit population sensitized to extremely low ethanol concentrations. USERs were created by mutating as few as four residues in the extracellular loop 2 region of glycine receptors (GlyRs) or γ-aminobutyric acid type A receptors (GABAARs), which are implicated in causing many behavioral effects linked to ethanol abuse. USERs, expressed in Xenopus oocytes and tested using two-electrode voltage clamp, demonstrated an increase in ethanol sensitivity of 100-fold over wild-type receptors by significantly decreasing the threshold and increasing the magnitude of ethanol response, without altering general receptor properties including sensitivity to the neurosteroid, allopregnanolone. These profound changes in ethanol sensitivity were observed across multiple subunits of GlyRs and GABAARs. Collectively, our studies set the stage for using USER technology in genetically engineered animals as a unique tool to increase understanding of the neurobiological basis of the behavioral effects of ethanol. PMID:25245406

  20. Abuse Liability Assessment of Tobacco Products Including Potential Reduced Exposure Products (PREPs)

    PubMed Central

    Carter, Lawrence P.; Stitzer, Maxine L.; Henningfield, Jack E.; O'Connor, Rich J.; Cummings, K. Michael; Hatsukami, Dorothy K.

    2009-01-01

    The harm produced by tobacco products is a result of frequent use of a highly toxic product. Reducing the adverse public health impact of tobacco products might be most effectively achieved by reducing the likelihood of their use and the toxicity of the products. Products that retain some characteristics of cigarettes, but have been altered with the intention of reducing toxicity have been referred to as modified risk tobacco products or potential reduced exposure products (MRTP/PREPS). Evaluation of their content, emission, and toxicity is discussed in other articles in this special issue. Here, we discuss the methodology that has been used to examine the likelihood of abuse or addiction. Abuse liability assessment (ALA) methodology has been used by the Food and Drug Administration (FDA) and other drug regulatory agencies world-wide for decades to assess the risks posed by a wide variety of pharmacologically active substances. ALA is routinely required among other evaluations of safety during the premarket assessment of new drugs, and is continually adapted to meet the challenges posed by new drug classes and drug formulations. In the 2009 law giving FDA regulation over tobacco products, FDA is now required to evaluate new tobacco products including MRTP/PREPs to determine their risk for abuse and toxicity at the population level. This paper describes the traditional tools and methods of ALA that can be used to evaluate new tobacco and nicotine products including MRTP/PREPs. Such ALA data could contribute to the scientific foundation on which future public policy decisions are based. PMID:19959676

  1. JNK pathway activation is controlled by Tao/TAOK3 to modulate ethanol sensitivity.

    PubMed

    Kapfhamer, David; King, Ian; Zou, Mimi E; Lim, Jana P; Heberlein, Ulrike; Wolf, Fred W

    2012-01-01

    Neuronal signal transduction by the JNK MAP kinase pathway is altered by a broad array of stimuli including exposure to the widely abused drug ethanol, but the behavioral relevance and the regulation of JNK signaling is unclear. Here we demonstrate that JNK signaling functions downstream of the Sterile20 kinase family gene tao/Taok3 to regulate the behavioral effects of acute ethanol exposure in both the fruit fly Drosophila and mice. In flies tao is required in neurons to promote sensitivity to the locomotor stimulant effects of acute ethanol exposure and to establish specific brain structures. Reduced expression of key JNK pathway genes substantially rescued the structural and behavioral phenotypes of tao mutants. Decreasing and increasing JNK pathway activity resulted in increased and decreased sensitivity to the locomotor stimulant properties of acute ethanol exposure, respectively. Further, JNK expression in a limited pattern of neurons that included brain regions implicated in ethanol responses was sufficient to restore normal behavior. Mice heterozygous for a disrupted allele of the homologous Taok3 gene (Taok3Gt) were resistant to the acute sedative effects of ethanol. JNK activity was constitutively increased in brains of Taok3Gt/+ mice, and acute induction of phospho-JNK in brain tissue by ethanol was occluded in Taok3Gt/+ mice. Finally, acute administration of a JNK inhibitor conferred resistance to the sedative effects of ethanol in wild-type but not Taok3Gt/+ mice. Taken together, these data support a role of a TAO/TAOK3-JNK neuronal signaling pathway in regulating sensitivity to acute ethanol exposure in flies and in mice.

  2. 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.

  3. Autoshaping of ethanol drinking: an animal model of binge drinking.

    PubMed

    Tomie, Arthur; di Poce, Jason; Derenzo, Christopher C; Pohorecky, Larissa A

    2002-01-01

    To examine the hypothesis that Pavlovian autoshaping provides an animal learning model of drug abuse, two studies evaluated the induction of ethanol drinking by autoshaping procedures. In Experiment 1, the sipper tube conditioned stimulus (CS) contained saccharin/ethanol solution and was repeatedly paired with food as an unconditioned stimulus (US). The CS-US paired group consumed more of the 0.1% saccharin-6% ethanol solution than did the CS-US random group, revealing that autoshaping conditioned responses (CR) induce ethanol drinking not attributable to pseudo-conditioning. Experiment 2 employed saccharin-fading procedures and showed that the paired vs random group differences in ethanol drinking were maintained, even as the saccharin was eliminated from the solution. The results show that Pavlovian autoshaping procedures induce high volumes of ethanol drinking when the presentation of a sipper tube containing an ethanol solution precedes the response-independent delivery of food. The high volume of ethanol consumed in a brief period of time suggests that Pavlovian autoshaping may be a model of binge drinking.

  4. Sex differences in adult Wistar rats in the voluntary consumption of ethanol after pre-exposure to ethanol-induced flavor avoidance learning.

    PubMed

    de la Torre, M Lourdes; Escarabajal, M Dolores; Agüero, Ángeles

    2015-10-01

    Vulnerability to ethanol abuse may be a function of the balance between the opposing (aversive and rewarding) motivational effects of the drug. The study of these effects is particularly important for understanding alcohol addiction. Research in this field seems to point out that ethanol effects are determined by a set of internal factors (sex, ethanol intake history, etc.), as well as by environmental conditions surrounding the individual (i.e., stress) and, of course, the interactions between all these factors. This work explores sex differences in sensitivity to aversive effects of ethanol using the procedure of flavor avoidance learning (FAL), as well as the effect of this learning experience on subsequent voluntary ethanol consumption, in adult rats. The results obtained indicated a slight sex based difference in the amount of FAL acquired in that females acquisition was weaker (experiment 1), and a differing influence of previous experience with the aversive effects of ethanol on the voluntary consumption of the drug for each sex (experiment 2). In particular, it was observed that female ethanol-naive rats showed a higher intake level and preference for ethanol than both ethanol-experienced female rats and ethanol-naive male rats. In contrast, the ethanol-experienced male rats showed a greater consumption of and preference for ethanol than ethanol-naive male rats and ethanol-experienced female rats. These data are discussed noting a range of possible explicative factors (sex hormones, hedonic processing, etc.), but further studies are warranted to elucidate the mechanisms by which ethanol pre-exposure influences the subsequent intake of ethanol differently by sex. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Distinct molecular targets including SLO-1 and gap junctions are engaged across a continuum of ethanol concentrations in Caenorhabditis elegans

    PubMed Central

    Dillon, James; Andrianakis, Ioannis; Mould, Richard; Ient, Ben; Liu, Wei; James, Christopher; O'Connor, Vincent; Holden-Dye, Lindy

    2013-01-01

    Ethanol (alcohol) interacts with diverse molecular effectors across a range of concentrations in the brain, eliciting intoxication through to sedation. Invertebrate models including the nematode worm Caenorhabditis elegans have been deployed for molecular genetic studies to inform on key components of these alcohol signaling pathways. C. elegans studies have typically employed external dosing with high (>250 mM) ethanol concentrations: A careful analysis of responses to low concentrations is lacking. Using the C. elegans pharyngeal system as a paradigm, we report a previously uncharacterized continuum of cellular and behavioral responses to ethanol from low (10 mM) to high (300 mM) concentrations. The complexity of these responses indicates that the pleiotropic action of ethanol observed in mammalian brain is conserved in this invertebrate model. We investigated two candidate ethanol effectors, the calcium-activated K+ channel SLO-1 and gap junctions, and show that they contribute to, but are not sole determinants of, the low- and high-concentration effects, respectively. Notably, this study shows cellular and whole organismal behavioral responses to ethanol in C. elegans that directly equate to intoxicating through to supralethal blood alcohol concentrations in humans and provides an important benchmark for interpretation of paradigms that seek to inform on human alcohol use disorders.—Dillon, J., Andrianakis, I., Mould, R., Ient, B., Liu, W., James, C., O'Connor, V., Holden-Dye, L. Distinct molecular targets including SLO-1 and gap junctions are engaged across a continuum of ethanol concentrations in Caenorhabditis elegans. PMID:23882127

  6. Effects of drugs of abuse on the central neuropeptide Y system.

    PubMed

    Gonçalves, Joana; Martins, João; Baptista, Sofia; Ambrósio, António Francisco; Silva, Ana Paula

    2016-07-01

    Neuropeptide Y (NPY), which is widely expressed in the central nervous system is involved in several neuropathologies including addiction. Here we comprehensively and systematically review alterations on the central NPY system induced by several drugs. We report on the effects of psychostimulants [cocaine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and nicotine], ethanol, and opioids on NPY protein levels and expression of different NPY receptors. Overall, expression and function of NPY and its receptors are changed under conditions of drug exposure, thus affecting several physiologic behaviors, such as feeding, stress and anxiety. Drugs of abuse differentially affect the components of the NPY system. For example methamphetamine and nicotine lead to a consistent increase in NPY mRNA and protein levels in different brain sites whereas ethanol and opioids decrease NPY mRNA and protein expression. Drug-induced alterations on the different NPY receptors show more complex regulation pattern. Manipulation of the NPY system can have opposing effects on reinforcing and addictive properties of drugs of abuse. NPY can produce pro-addictive effects (nicotine and heroin), but can also exert inhibitory effects on addictive behavior (AMPH, ethanol). Furthermore, NPY can act as a neuroprotective agent in chronically methamphetamine and MDMA-treated rodents. In conclusion, manipulation of the NPY system seems to be a potential target to counteract neural alterations, addiction-related behaviors and cognitive deficits induced by these drugs. © 2015 Society for the Study of Addiction.

  7. Repeated Cycles of Binge-Like Ethanol Drinking in Male C57BL/6J Mice Augments Subsequent Voluntary Ethanol Intake But Not Other Dependence-Like Phenotypes

    PubMed Central

    Cox, Benjamin R.; Olney, Jeffrey J.; Lowery-Gionta, Emily G.; Sprow, Gretchen M.; Rinker, Jennifer A.; Navarro, Montserrat; Kash, Thomas L.; Thiele, Todd E.

    2013-01-01

    Background Recently, procedures have been developed to model specific facets of human alcohol abuse disorders, including those that model excessive binge-like drinking (i.e., “drinking in the dark”, or DID procedures) and excessive dependence-like drinking (i.e., intermittent ethanol vapor exposure). Similar neuropeptide systems modulate excessive ethanol drinking stemming from both procedures, raising the possibility that both paradigms are actually modeling the same phenotypes and triggering the same central neuroplasticity. Therefore, the goal of the present project was to study the effects of a history of binge-like ethanol drinking, using DID procedures, on phenotypes that have previously been described with procedures to model dependence-like drinking. Methods Male C57BL/6J mice first experienced 0 to 10 4-day binge-like drinking episodes (3 days of rest between episodes). Beginning 24-h after the final binge-like drinking session, mice were tested for anxiety-like behaviors (with elevated plus maze (EPM) and open-field locomotor activity tests), ataxia with the rotarod test, and sensitivity to handling-induced convulsions (HICs). One week later, mice began a 40-day 2-bottle (water versus ethanol) voluntary consumption test with concentration ranging from 10 to 20% (v/v) ethanol. Results A prior history of binge-like ethanol drinking significantly increased subsequent voluntary ethanol consumption and preference, effects most robust in groups that initially experienced 6 or 10 binge-like drinking episodes and completely absent in mice that experienced 1 binge-like drinking episode. Conversely, a history of binge-like ethanol drinking did not influence anxiety-like behaviors, ataxia, or HICs. Conclusions Excessive ethanol drinking stemming from DID procedures does not initially induce phenotypes consistent with a dependence-like state. However, the subsequent increases of voluntary ethanol consumption and preference that become more robust following

  8. Increased ethanol consumption after interruption of fat bingeing.

    PubMed

    Blanco-Gandía, M Carmen; Miñarro, José; Aguilar, Maria Asuncion; Rodríguez-Arias, Marta

    2018-01-01

    There is a marked comorbidity between alcohol abuse and eating disorders, especially in the young population. We have previously reported that bingeing on fat during adolescence increases the rewarding effects of ethanol (EtOH). The aim of the present work was to study if vulnerability to EtOH persists after cessation of binge eating. OF1 mice binged on fat (HFB: high-fat binge) during adolescence (PND 25-43) and were tested for 15 days after the last access to HFB (on PND 59) using the self-administration paradigm, the conditioned place preference (CPP) and locomotor sensitization to ethanol. Our results showed that after 15 days of cessation of fat ingestion, mice increased their consumption of ethanol and showed greater motivation to obtain ethanol. On the other hand, no effects were observed in the CPP, while an increased locomotor response to ethanol was detected. The present results confirm and extend our previous study demonstrating that the compulsive intake of fat induces long-lasting effects on the reward system that lead to an increased consumption of EtOH.

  9. Increased ethanol consumption after interruption of fat bingeing

    PubMed Central

    Blanco-Gandía, M. Carmen; Miñarro, José; Aguilar, Maria Asuncion

    2018-01-01

    There is a marked comorbidity between alcohol abuse and eating disorders, especially in the young population. We have previously reported that bingeing on fat during adolescence increases the rewarding effects of ethanol (EtOH). The aim of the present work was to study if vulnerability to EtOH persists after cessation of binge eating. OF1 mice binged on fat (HFB: high-fat binge) during adolescence (PND 25–43) and were tested for 15 days after the last access to HFB (on PND 59) using the self-administration paradigm, the conditioned place preference (CPP) and locomotor sensitization to ethanol. Our results showed that after 15 days of cessation of fat ingestion, mice increased their consumption of ethanol and showed greater motivation to obtain ethanol. On the other hand, no effects were observed in the CPP, while an increased locomotor response to ethanol was detected. The present results confirm and extend our previous study demonstrating that the compulsive intake of fat induces long-lasting effects on the reward system that lead to an increased consumption of EtOH. PMID:29590149

  10. Model of voluntary ethanol intake in zebrafish: Effect on behavior and hypothalamic orexigenic peptides

    PubMed Central

    Sterling, M.E.; Karatayev, O.; Chang, G.-Q.; Algava, D.B.; Leibowitz, S.F

    2014-01-01

    Recent studies in zebrafish have shown that exposure to ethanol in tank water affects various behaviors, including locomotion, anxiety and aggression, and produces changes in brain neurotransmitters, such as serotonin and dopamine. Building on these investigations, the present study had two goals: first, to develop a method for inducing voluntary ethanol intake in individual zebrafish, which can be used as a model in future studies to examine how this behavior is affected by various manipulations, and second, to characterize the effects of this ethanol intake on different behaviors and the expression of hypothalamic orexigenic peptides, galanin (GAL) and orexin (OX), which are known in rodents to stimulate consumption of ethanol and alter behaviors associated with alcohol abuse. Thus, we first developed a new model of voluntary intake of ethanol in fish by presenting this ethanol mixed with gelatin, which they readily consume. Using this model, we found that individual zebrafish can be trained in a short period of time to consume stable levels of 10% or 20% ethanol (v/v) mixed with gelatin and that their intake of this ethanol-gelatin mixture leads to pharmacologically-relevant blood ethanol concentrations which are strongly, positively correlated with the amount ingested. Intake of this ethanol-gelatin mixture increased locomotion, reduced anxiety, and stimulated aggressive behavior, while increasing expression of GAL and OX in specific hypothalamic areas. These findings, confirming results in rats, provide a method in zebrafish for investigating with forward genetics and pharmacological techniques the role of different brain mechanisms in controlling ethanol intake. PMID:25257106

  11. Helplessness in the tail suspension test is associated with an increase in ethanol intake and its rewarding effect in female mice.

    PubMed

    Pelloux, Yann; Hagues, Guillaume; Costentin, Jean; Duterte-Boucher, Dominique

    2005-03-01

    Depression is frequently observed in drug abusers. However, depression may be a primary factor of predisposition to drug abuse or a consequence of drug abuse. The aim of this study was to analyze the influence of a preexisting depressive-like state/helplessness on subsequent alcohol responsiveness in mice. Male and female CD1 mice were selected according to their immobility time in the tail suspension test, and only mice with "high immobility" and "low immobility" time were retained. Using a two-bottle free-choice paradigm, these mice were given continuous access to tap water or solutions of ethanol (3-20% v/v), quinine (12.5-50 mg/liter), or sucrose (1-4% w/v). In female mice, rewarding and aversive effects of ethanol (1.5 and 3 g/kg, intraperitoneally) were also investigated using the conditioned place preference and the conditioned taste aversion paradigms. Female mice were more immobile and drank more ethanol than male mice. No striking sex difference was observed in quinine consumption. Sucrose intake was higher in female than in male mice, whatever the solution concentration. At the 4% concentrated solution, a sucrose-induced increase in daily fluid intake was observed only in female mice. Female mice with high immobility time (HI) consumed more ethanol at the highest concentration than female mice with low immobility time (LI), whereas no difference was observed between HI and LI male mice. Moreover, whereas LI female mice failed to express place conditioning induced by the 3-g/kg dose of ethanol, HI female mice were strongly responsive to the rewarding effect of this high ethanol dose. Ethanol dose-dependently induced a conditioned taste aversion with a similar magnitude in both LI and HI female mice. The findings indicate that female CD1 mice tend to drink greater amounts of ethanol or sucrose solutions than male CD1 mice, suggesting that female mice may be a better model of excessive alcohol intake. Furthermore, no relationship was found between

  12. Chronobiology of ethanol: animal models.

    PubMed

    Rosenwasser, Alan M

    2015-06-01

    Clinical and epidemiological observations have revealed that alcohol abuse and alcoholism are associated with widespread disruptions in sleep and other circadian biological rhythms. As with other psychiatric disorders, animal models have been very useful in efforts to better understand the cause and effect relationships underlying the largely correlative human data. This review summarizes the experimental findings indicating bidirectional interactions between alcohol (ethanol) consumption and the circadian timing system, emphasizing behavioral studies conducted in the author's laboratory. Together with convergent evidence from multiple laboratories, the work summarized here establishes that ethanol intake (or administration) alters fundamental properties of the underlying circadian pacemaker. In turn, circadian disruption induced by either environmental or genetic manipulations can alter voluntary ethanol intake. These reciprocal interactions may create a vicious cycle that contributes to the downward spiral of alcohol and drug addiction. In the future, such studies may lead to the development of chronobiologically based interventions to prevent relapse and effectively mitigate some of the societal burden associated with such disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Increased ethanol self-administration after a period of imposed ethanol deprivation in rats trained in a limited access paradigm.

    PubMed

    Heyser, C J; Schulteis, G; Koob, G F

    1997-08-01

    A predominant feature in human alcohol abuse is the reported desire or "craving" to consume ethanol along with frequent episodes of drinking after periods of abstinence. These and other factors may be responsible for relapse to uncontrolled ethanol drinking. When relapse occurs after a period of abstinence, ethanol drinking has been shown to be temporarily increased. Two aspects of drug dependence could contribute to these increases. One may be the development of a need state; the other may involve changes in the perception of the positive reinforcing effects of ethanol when reinforcer access is limited. To investigate this phenomenon further, the present study was conducted to examine in nondependent rats the effect of forced time-off on oral ethanol self-administration in a limited access paradigm (30 min/day). Male Wistar rats were trained to respond for ethanol (10% w/v) or water in a two-lever, free-choice condition using a saccharin fading procedure. After the establishment of stable baseline responding for ethanol, various ethanol deprivation periods (3, 5, 7, 14, or 28 days) were imposed, during which no ethanol was available. Responding for ethanol increased as a function of the duration of the deprivation period when compared with baseline levels. This increase was temporary and returned to baseline levels within 2 to 3 days. Given that the shortest time-off period was 5 days and the rats showed no signs of withdrawal, this transient increase in ethanol responding does not seem to be related to the manifestation of dependence and withdrawal, and may be related to changes in ethanol's reinforcement properties. These results with rats may provide a useful tool to elucidate mechanisms underlying human alcohol seeking behavior and relapse.

  14. Drug Abuse Education Program. Drug Abuse Education, Grades 5,7,9. Bibliography Included.

    ERIC Educational Resources Information Center

    Baltimore City Public Schools, MD.

    A drug abuse education program was implemented in grades five, seven, and nine in the Baltimore City Public Schools. Unit plans outline the curriculum content and learning activities for each of the three grades. The major objective in grade five is to familiarize pupils with various medically used drugs and to develop an understanding that they…

  15. Chronic intermittent ethanol exposure selectively alters the expression of Gα subunit isoforms and RGS subtypes in rat prefrontal cortex.

    PubMed

    Luessen, D J; Sun, H; McGinnis, M M; McCool, B A; Chen, R

    2017-10-01

    Chronic alcohol exposure induces pronounced changes in GPCR-mediated G-protein signaling. Recent microarray and RNA-seq analyses suggest associations between alcohol abuse and the expression of genes involved in G-protein signaling. The activity of G-proteins (e.g. Gαi/o and Gαq) is negatively modulated by regulator of G-protein signaling (RGS) proteins which are implicated in drugs of abuse including alcohol. The present study used 7days of chronic intermittent ethanol exposure followed by 24h withdrawal (CIE) to investigate changes in mRNA and protein levels of G-protein subunit isoforms and RGS protein subtypes in rat prefrontal cortex, a region associated with cognitive deficit attributed to excessive alcohol drinking. We found that this ethanol paradigm induced differential expression of Gα subunits and RGS subtypes. For example, there were increased mRNA and protein levels of Gαi1/3 subunits and no changes in the expression of Gαs and Gαq subunits in ethanol-treated animals. Moreover, CIE increased the mRNA but not the protein levels of Gαo. Additionally, a modest increase in Gαi2 mRNA level by CIE was accompanied by a pronounced increase in its protein level. Interestingly, we found that CIE increased mRNA and protein levels of RGS2, RGS4, RGS7 and RGS19 but had no effect on the expression of RGS5, RGS6, RGS8, RGS12 or RGS17. Changes in the expression of Gα subunits and RGS subtypes could contribute to the functional alterations of certain GPCRs following chronic ethanol exposure. The present study suggests that RGS proteins may be potential new targets for intervention of alcohol abuse via modification of Gα-mediated GPCR function. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. New, previously unreported correlations between latent Toxoplasma gondii infection and excessive ethanol consumption.

    PubMed

    Samojłowicz, Dorota; Borowska-Solonynko, Aleksandra; Kruczyk, Marcin

    2017-11-01

    A number of world literature reports indicate that a latent Toxoplasma gondii infection leads to development of central nervous system disorders, which in turn may lead to altered behavior in the affected individuals. T. gondii infection has been observed to play the greatest role in drivers, suicides, and psychiatric patients. Studies conducted for this manuscript involve a different, never before really reported correlation between latent T. gondii infection and ethanol abuse. A total of 538 decedents with a known cause of death were included in the study. These individuals were divided into three groups: the risky behavior group, inconclusively risky behavior group, and control group. The criterion for this division was the likely effect of the individual's behavior on the mechanism and cause of his/her death. The material used for analyses were blood samples collected during routine medico-legal examinations in these cases. The blood samples were used to measure anti-T. gondii IgG antibodies with an enzyme-linked immunosorbent assay (ELISA). Moreover, the following data were recorded for each decedent: sex, age, circumstances of death, cause of death, time from death to autopsy, and (if provided) substance abuse status (alcohol, illicit drugs). In those cases where blood alcohol level or toxicology tests were requested by the Prosecutor's Office, their results were also included in our analysis. Test results demonstrated a strong correlation between latent T. gondii infection and engaging in risky behaviors leading to death. Moreover, analyses demonstrated a positive correlation between the presence of anti-T. gondii IgG antibodies and psychoactive substance (especially ethanol) abuse, however, the causal relationship remains unclear. Due to the fact that alcohol abuse constitutes a significant social problem, searching for eliminable risk factors for addiction is extremely important. Our analyses provided new important information on the possible effects of

  17. Assessing appetitive, aversive, and negative ethanol-mediated reinforcement through an immature rat model.

    PubMed

    Pautassi, Ricardo M; Nizhnikov, Michael E; Spear, Norman E

    2009-06-01

    The motivational effects of drugs play a key role during the transition from casual use to abuse and dependence. Ethanol reinforcement has been successfully studied through Pavlovian and operant conditioning in adult rats and mice genetically selected for their ready acceptance of ethanol. Another model for studying ethanol reinforcement is the immature (preweanling) rat, which consumes ethanol and exhibits the capacity to process tactile, odor and taste cues and transfer information between different sensorial modalities. This review describes the motivational effects of ethanol in preweanling, heterogeneous non-selected rats. Preweanlings exhibit ethanol-mediated conditioned taste avoidance and conditioned place aversion. Ethanol's appetitive effects, however, are evident when using first- and second-order conditioning and operant procedures. Ethanol also devalues the motivational representation of aversive stimuli, suggesting early negative reinforcement. It seems that preweanlings are highly sensitive not only to the aversive motivational effects of ethanol but also to its positive and negative (anti-anxiety) reinforcement potential. The review underscores the advantages of using a developing rat to evaluate alcohol's motivational effects.

  18. Assessing appetitive, aversive, and negative ethanol-mediated reinforcement through an immature rat model

    PubMed Central

    Pautassi, Ricardo M.; Nizhnikov, Michael E.; Spear, Norman E.

    2009-01-01

    The motivational effects of drugs play a key role during the transition from casual use to abuse and dependence. Ethanol reinforcement has been successfully studied through Pavlovian and operant conditioning in adult rats and mice genetically selected for their ready acceptance of ethanol. Another model for studying ethanol reinforcement is the immature (preweanling) rat, which consumes ethanol and exhibits the capacity to process tactile, odor and taste cues and transfer information between different sensorial modalities. This review describes the motivational effects of ethanol in preweanling, heterogeneous non-selected rats. Preweanlings exhibit ethanol-mediated conditioned taste avoidance and conditioned place aversion. Ethanol's appetitive effects, however, are evident when using first- and second-order conditioning and operant procedures. Ethanol also devalues the motivational representation of aversive stimuli, suggesting early negative reinforcement. It seems that preweanlings are highly sensitive not only to the aversive motivational effects of ethanol but also to its positive and negative (anti-anxiety) reinforcement potential. The review underscores the advantages of using a developing rat to evaluate alcohol's motivational effects. PMID:19428502

  19. Role of Adrenal Glucocorticoid Signaling in Prefrontal Cortex Gene Expression and Acute Behavioral Responses to Ethanol

    PubMed Central

    Costin, Blair N.; Wolen, Aaron R.; Fitting, Sylvia; Shelton, Keith L.; Miles, Michael F.

    2012-01-01

    Background Glucocorticoid hormones modulate acute and chronic behavioral and molecular responses to drugs of abuse including psychostimulants and opioids. There is growing evidence that glucocorticoids might also modulate behavioral responses to ethanol. Acute ethanol activates the HPA axis, causing release of adrenal glucocorticoid hormones. Our prior genomic studies suggest glucocorticoids play a role in regulating gene expression in the prefrontal cortex (PFC) of DBA2/J (D2) mice following acute ethanol administration. However, few studies have analyzed the role of glucocorticoid signaling in behavioral responses to acute ethanol. Such work could be significant, given the predictive value for level of response to acute ethanol in the risk for alcoholism. Methods We studied whether the glucocorticoid receptor (GR) antagonist, RU-486, or adrenalectomy (ADX) altered male D2 mouse behavioral responses to acute (locomotor activation, anxiolysis or loss-of-righting reflex (LORR)) or repeated (sensitization) ethanol treatment. Whole genome microarray analysis and bioinformatics approaches were used to identify PFC candidate genes possibly responsible for altered behavioral responses to ethanol following ADX. Results ADX and RU-486 both impaired acute ethanol (2 g/kg) induced locomotor activation in D2 mice without affecting basal locomotor activity. However, neither ADX nor RU-486 altered initiation of ethanol sensitization (locomotor activation or jump counts), ethanol-induced anxiolysis or LORR. ADX mice showed microarray gene expression changes in PFC that significantly overlapped with acute ethanol-responsive gene sets derived by our prior microarray studies. Q-rtPCR analysis verified that ADX decreased PFC expression of Fkbp5 while significantly increasing Gpr6 expression. In addition, high dose RU-486 pre-treatment blunted ethanol-induced Fkbp5 expression. Conclusions Our studies suggest that ethanol’s activation of adrenal glucocorticoid release and subsequent

  20. The economics of alcohol abuse and alcohol-control policies.

    PubMed

    Cook, Philip J; Moore, Michael J

    2002-01-01

    Economic research has contributed to the evaluation of alcohol policy through empirical analysis of the effects of alcohol-control measures on alcohol consumption and its consequences. It has also provided an accounting framework for defining and comparing costs and benefits of alcohol consumption and related policy interventions, including excise taxes. The most important finding from the economics literature is that consumers tend to drink less ethanol, and have fewer alcohol-related problems, when alcoholic beverage prices are increased or alcohol availability is restricted. That set of findings is relevant for policy purposes because alcohol abuse imposes large "external" costs on others. Important challenges remain, including developing a better understanding of the effects of drinking on labor-market productivity.

  1. Effects of adolescent onset voluntary drinking followed by ethanol vapor exposure on subsequent ethanol consumption during protracted withdrawal in adult Wistar rats.

    PubMed

    Criado, Jose R; Ehlers, Cindy L

    2013-01-01

    Epidemiological studies have demonstrated that heavy drinking and alcohol abuse and dependence peak during the transition between late adolescence and early adulthood. The objective of the present study was to determine whether a model of early onset adolescent ethanol drinking exposure that is followed by an ethanol vapor regimen during late adolescence and young adulthood leads to an increase in drinking in adulthood. In this model, initiation of voluntary ethanol drinking in adolescence, using a sweetened solution, was followed by an 8-wk intermittent ethanol vapor regimen in Wistar rats. A limited-access two-bottle choice paradigm was then used to measure intake of a 10% (w/v) ethanol solution. No differences in water intake (g/kg), total fluid intake (ml/kg) and body weight (g) were observed between air-exposed and ethanol-vapor exposed groups during the pre-vapor and post-vapor phases. The 8 weeks of ethanol vapor exposure was found to produce only a modest, but statistically significant, elevation of ethanol intake during the protracted withdrawal period, compared to air-exposed rats. A significant increase in ethanol preference ratio was also observed in ethanol-vapor exposed rats during the sucrose-fading phase, but not during the protracted withdrawal period. The findings from the present study suggest that in addition to alcohol exposure, environmental variables that impact appetitive as well as consumptive behaviors may be important in developing robust drinking effects that model, in animals, the increased risk for alcohol dependence seen in some human adolescents who begin drinking at an early age. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Effects of adolescent onset voluntary drinking followed by ethanol vapor exposure on subsequent ethanol consumption during protracted withdrawal in adult Wistar rats

    PubMed Central

    Criado, Jose R.; Ehlers, Cindy L.

    2012-01-01

    Epidemiological studies have demonstrated that heavy drinking and alcohol abuse and dependence peak during the transition between late adolescence and early adulthood. The objective of the present study was to determine whether a model of early onset adolescent ethanol drinking exposure that is followed by an ethanol vapor regimen during late adolescence and young adulthood leads to an increase in drinking in adulthood. In this model, initiation of voluntary ethanol drinking in adolescence, using a sweetened solution, was followed by an 8-wk intermittent ethanol vapor regimen in Wistar rats. A limited-access two-bottle choice paradigm was then used to measure intake of a 10% (w/v) ethanol solution. No differences in water intake (g/kg), total fluid intake (ml/kg) and body weight (g) were observed between air-exposed and ethanol-vapor exposed groups during the pre-vapor and post-vapor phases. The eight wks of ethanol vapor exposure was found to produce only a modest, but statistically significant, elevation of ethanol intake during the protracted withdrawal period, compared to air-exposed rats. A significant increase in ethanol preference ratio was also observed in ethanol-vapor exposed rats during the sucrose-fading phase, but not during the protracted withdrawal period. The findings from the present study suggest that in addition to alcohol exposure, environmental variables that impact appetitive as well as consumptive behaviors may be important in developing robust drinking effects that model, in animals, the increased risk for alcohol dependence seen in some human adolescents who begin drinking at an early age. PMID:23128022

  3. Forced swim stress increases ethanol consumption in C57BL/6J mice with a history of chronic intermittent ethanol exposure.

    PubMed

    Anderson, Rachel I; Lopez, Marcelo F; Becker, Howard C

    2016-06-01

    Stress exposure has been identified as one risk factor for alcohol abuse that may facilitate the transition from social or regulated alcohol use to the development of alcohol dependence. Additionally, stress is a common trigger for relapse and subsequent loss of control of drinking in alcohol-dependent individuals. The present study was designed to characterize effects of repeated forced swim stress (FSS) on ethanol consumption in three rodent drinking models that engender high levels of ethanol consumption. Adult male C57BL/6J mice were exposed to 10-min FSS 4 h prior to each drinking session in three different models of high ethanol consumption: chronic intermittent ethanol (CIE) drinking (a model of dependence-like drinking), drinking-in-the-dark (DID; a model of binge-like drinking), and intermittent vs. continuous access (a model of escalated drinking). In the CIE drinking paradigm, daily FSS facilitated the escalation of ethanol intake that is typically seen in CIE-exposed mice without altering ethanol consumption in control mice exposed to FSS. FSS prior to drinking sessions did not alter ethanol consumption in the DID or intermittent access paradigms, whereas stressed mice in the continuous access procedure consumed less ethanol than their nonstressed counterparts. The CIE drinking paradigm may provide a helpful preclinical model of stress-induced transition to ethanol dependence that can be used to (1) identify underlying neural mechanisms that facilitate this transition and (2) evaluate the therapeutic potential of various pharmacological agents hypothesized to alleviate stress-induced drinking.

  4. Toxicology and the biological role of methanol and ethanol: Current view.

    PubMed

    Pohanka, Miroslav

    2016-03-01

    Alcohol variants such as ethanol and methanol are simple organic compounds widely used in foods, pharmaceuticals, chemical synthesis, etc. Both are becoming an emerging health problem; abuse of ethanol containing beverages can lead to disparate health problems and methanol is highly toxic and unfit for consumption. This review summarizes the basic knowledge about ethanol and methanol toxicity, the effect mechanism on the body, the current care of poisoned individuals and the implication of alcohols in the development of diseases. Alcohol related dementia, stroke, metabolic syndrome and hepatitis are discussed as well. Besides ethanol, methanol toxicity and its biodegradation pathways are addressed. The impact of ethanol and methanol on the body is shown as case reports, along with a discussion on the possible implication of alcohol in Alzheimer's disease and antidotal therapy for methanol poisoning. The role of ethanol in cancer and degenerative disorders seems to be underestimated given the current knowledge. Treatment in case of poisoning is another issue that remains unresolved even though effective protocols and drugs exist.

  5. Adenosine signaling contributes to ethanol-induced fatty liver in mice

    PubMed Central

    Peng, Zhongsheng; Borea, Pier Andrea; Wilder, Tuere; Yee, Herman; Chiriboga, Luis; Blackburn, Michael R.; Azzena, Gianfranco; Resta, Giuseppe; Cronstein, Bruce N.

    2009-01-01

    Fatty liver is commonly associated with alcohol ingestion and abuse. While the molecular pathogenesis of these fatty changes is well understood, the biochemical and pharmacological mechanisms by which ethanol stimulates these molecular changes remain unknown. During ethanol metabolism, adenosine is generated by the enzyme ecto-5′-nucleotidase, and adenosine production and adenosine receptor activation are known to play critical roles in the development of hepatic fibrosis. We therefore investigated whether adenosine and its receptors play a role in the development of alcohol-induced fatty liver. WT mice fed ethanol on the Lieber-DeCarli diet developed hepatic steatosis, including increased hepatic triglyceride content, while mice lacking ecto-5′-nucleotidase or adenosine A1 or A2B receptors were protected from developing fatty liver. Similar protection was also seen in WT mice treated with either an adenosine A1 or A2B receptor antagonist. Steatotic livers demonstrated increased expression of genes involved in fatty acid synthesis, which was prevented by blockade of adenosine A1 receptors, and decreased expression of genes involved in fatty acid metabolism, which was prevented by blockade of adenosine A2B receptors. In vitro studies supported roles for adenosine A1 receptors in promoting fatty acid synthesis and for A2B receptors in decreasing fatty acid metabolism. These results indicate that adenosine generated by ethanol metabolism plays an important role in ethanol-induced hepatic steatosis via both A1 and A2B receptors and suggest that targeting adenosine receptors may be effective in the prevention of alcohol-induced fatty liver. PMID:19221436

  6. Activation of cardiac fibroblasts by ethanol is blocked by TGF-β inhibition

    PubMed Central

    Law, Brittany A.; Carver, Wayne E.

    2013-01-01

    Background Alcohol abuse is the second leading cause of dilated cardiomyopathy, a disorder specifically referred to as Alcoholic Cardiomyopathy (ACM). Rodent and human studies have revealed cardiac fibrosis to be a consequence of ACM and prior studies by this lab have associated this occurrence with elevated transforming growth factor-beta (TGF-β) and activated fibroblasts (myofibroblasts). To date there have been no other studies to investigate the direct effect of alcohol on the cardiac fibroblast. Methods Primary rat cardiac fibroblasts were cultured in the presence of ethanol and assayed for fibroblast activation by collagen gel contraction, alpha smooth muscle- actin (α-SMA) expression, migration, proliferation, apoptosis, collagen I & III and TGF-β expression. The TGF-β receptor type 1 inhibitor compound SB 431542 and a soluble recombinant TGF-βII receptor (RbII) were used to assess the role of of TGF-β in the response of cardiac fibroblasts to ethanol. Results Treatment of cardiac fibroblasts with ethanol at concentrations of 100 mg/dl or higher resulted in fibroblast activation and fibrogenic activity after 24 hours including an increase in contraction, α-SMA expression, migration, and expression of collagen I and TGF-β. No changes in fibroblast proliferation or apoptosis were observed. Inhibition of TGF-β by SB 431542 and RbII attenuated the ethanol-induced fibroblast activation. Conclusions Ethanol treatment directly promotes cardiac fibroblast activation by stimulating TGF-β release from fibroblasts. Inhibiting the action of TGF-β decreases the fibrogenic effect induced by ethanol treatment. The results of this study support TGF-β to be an important component in cardiac fibrosis induced by exposure to ethanol. PMID:23528014

  7. Ethanol Effects on Dopaminergic Ventral Tegmental Area Neurons During Block of Ih: Involvement of Barium-Sensitive Potassium Currents

    PubMed Central

    McDaid, John; McElvain, Maureen A.; Brodie, Mark S.

    2008-01-01

    The dopaminergic neurons of the ventral tegmental area (DA VTA neurons) are important for the rewarding and reinforcing properties of drugs of abuse, including ethanol. Ethanol increases the firing frequency of DA VTA neurons from rats and mice. Because of a recent report on block of ethanol excitation in mouse DA VTA neurons with ZD7288, a selective blocker of the hyperpolarization-activated cationic current Ih, we examined the effect of ZD7288 on ethanol excitation in DA VTA neurons from C57Bl/6J and DBA/2J mice and Fisher 344 rats. Ethanol (80 mM) caused only increases in firing rate in mouse DA VTA neurons in the absence of ZD7288, but in the presence of ZD7288 (30 μM), ethanol produced a more transient excitation followed by a decrease of firing. This same biphasic phenomenon was observed in DA VTA neurons from rats in the presence of ZD7288 only at very high ethanol concentrations (160–240 mM) but not at lower pharmacologically relevant concentrations. The longer latency ethanol-induced inhibition was not observed in DA VTA neurons from mice or rats in the presence of barium (100 μM), which blocks G protein–linked potassium channels (GIRKs) and other inwardly rectifying potassium channels. Ethanol may have a direct effect to increase an inhibitory potassium conductance, but this effect of ethanol can only decrease the firing rate if Ih is blocked. PMID:18614756

  8. Effects of Ethanol on the Cerebellum: Advances and Prospects.

    PubMed

    Luo, Jia

    2015-08-01

    Alcohol abuse causes cerebellar dysfunction and cerebellar ataxia is a common feature in alcoholics. Alcohol exposure during development also impacts the cerebellum. Children with fetal alcohol spectrum disorder (FASD) show many symptoms associated specifically with cerebellar deficits. However, the cellular and molecular mechanisms are unclear. This special issue discusses the most recent advances in the study of mechanisms underlying alcoholinduced cerebellar deficits. The alteration in GABAA receptor-dependent neurotransmission is a potential mechanism for ethanol-induced cerebellar dysfunction. Recent advances indicate ethanol-induced increases in GABA release are not only in Purkinje cells (PCs), but also in molecular layer interneurons and granule cells. Ethanol is shown to disrupt the molecular events at the mossy fiber - granule cell - Golgi cell (MGG) synaptic site and granule cell parallel fibers - PCs (GPP) synaptic site, which may be responsible for ethanol-induced cerebellar ataxia. Aging and ethanol may affect the smooth endoplasmic reticulum (SER) of PC dendrites and cause dendritic regression. Ethanol withdrawal causes mitochondrial damage and aberrant gene modifications in the cerebellum. The interaction between these events may result in neuronal degeneration, thereby contributing to motoric deficit. Ethanol activates doublestranded RNA (dsRNA)-activated protein kinase (PKR) and PKR activation is involved ethanolinduced neuroinflammation and neurotoxicity in the developing cerebellum. Ethanol alters the development of cerebellar circuitry following the loss of PCs, which could result in modifications of the structure and function of other brain regions that receive cerebellar inputs. Lastly, choline, an essential nutrient is evaluated for its potential protection against ethanol-induced cerebellar damages. Choline is shown to ameliorate ethanol-induced cerebellar dysfunction when given before ethanol exposure.

  9. Cilnidipine, an L/N-type calcium channel blocker prevents acquisition and expression of ethanol-induced locomotor sensitization in mice.

    PubMed

    Bhutada, Pravinkumar; Mundhada, Yogita; Patil, Jayshree; Rahigude, Anand; Zambare, Krushna; Deshmukh, Prashant; Tanwar, Dhanshree; Jain, Kishor

    2012-04-11

    Several evidences indicated the involvement of L- and N-type calcium channels in behavioral effects of drugs of abuse, including ethanol. Calcium channels are implicated in ethanol-induced behaviors and neurochemical responses. Calcium channel antagonists block the psychostimulants induced behavioral sensitization. Recently, it is demonstrated that L-, N- and T-type calcium channel blockers attenuate the acute locomotor stimulant effects of ethanol. However, no evidence indicated the role of calcium channels in ethanol-induced psychomotor sensitization. Therefore, present study evaluated the influence of cilnidipine, an L/N-type calcium channel blocker on acquisition and expression of ethanol-induced locomotor sensitization. The results revealed that cilnidipine (0.1 and 1.0μg/mouse, i.c.v.) attenuates the expression of sensitization to locomotor stimulant effect of ethanol (2.0g/kg, i.p.), whereas pre- treatment of cilnidipine (0.1 and 1.0μg/mouse, i.c.v.) during development of sensitization blocks acquisition and attenuates expression of sensitization to locomotor stimulant effect of ethanol. Cilnidipine per se did not influence locomotor activity in tested doses. Further, cilnidipine had no influence on effect of ethanol on rotarod performance. These results support the hypothesis that neuroadaptive changes in calcium channels participate in the acquisition and the expression of ethanol-induced locomotor sensitization. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. Elder Abuse

    MedlinePlus

    ... homes. The mistreatment may be Physical, sexual, or emotional abuse Neglect or abandonment Financial abuse - stealing of money or belongings Possible signs of elder abuse include unexplained bruises, burns, and injuries. There ...

  11. Comparative Ethanol-Induced Potentiation of Stimulatory Responses to Dexmethylphenidate Versus Methylphenidate.

    PubMed

    Patrick, Kennerly S; Straughn, Arthur B; Reeves, Owen T; Bernstein, Hilary; Malcolm, Robert

    2015-08-01

    The potentiation of positive subjective responses to immediate-release dexmethylphenidate (d-MPH) or dl-methylphenidate (dl-MPH) by ethanol was investigated over the time course of maximal drug exposure after a single dose. In a 4-way, randomized, crossover study design, 12 men and 12 women normal volunteers received d-MPH (0.15 mg/kg) or dl-MPH (0.3 mg/kg) with or without ethanol (0.6 g/kg). Serial visual analog scales were used as surrogates for drug abuse liability ("high," "good," "like," "stimulated," and "any drug effect"). Combining pure d-MPH with ethanol significantly (P < 0.005) increased the area under the effect curves (AUC(0-5.25h)) of all 5 subscales. The dl-MPH-ethanol combination significantly (P < 0.05) increased these AUCs with the exception of like (P = 0.08). Effects of the pure d-MPH-ethanol combination exhibited delayed potentiation relative to dl-MPH-ethanol. A pharmacokinetic interaction between the l-isomer of dl-MPH and ethanol has previously been shown to increase early exposure to d-MPH. Administration of the pure isomer d-MPH precludes this absorption phase pharmacokinetic interaction with ethanol. This notwithstanding, the pure d-MPH-ethanol combination resulted in comparable, if not greater, cumulative stimulant potentiation than the dl-MPH-ethanol combination. These findings provide evidence of a pharmacodynamic component to d-MPH-ethanol synergistic interactions and carry implications for the rational drug individualization in the treatment of attention-deficit/hyperactivity disorder.

  12. Ethanol Seeking by Long Evans Rats Is Not Always a Goal-Directed Behavior

    PubMed Central

    Mangieri, Regina A.; Cofresí, Roberto U.; Gonzales, Rueben A.

    2012-01-01

    Background Two parallel and interacting processes are said to underlie animal behavior, whereby learning and performance of a behavior is at first via conscious and deliberate (goal-directed) processes, but after initial acquisition, the behavior can become automatic and stimulus-elicited (habitual). With respect to instrumental behaviors, animal learning studies suggest that the duration of training and the action-outcome contingency are two factors involved in the emergence of habitual seeking of “natural” reinforcers (e.g., sweet solutions, food or sucrose pellets). To rigorously test whether behaviors reinforced by abused substances such as ethanol, in particular, similarly become habitual was the primary aim of this study. Methodology/Principal Findings Male Long Evans rats underwent extended or limited operant lever press training with 10% sucrose/10% ethanol (10S10E) reinforcement (variable interval (VI) or (VR) ratio schedule of reinforcement), or with 10% sucrose (10S) reinforcement (VI schedule only). Once training and pretesting were complete, the impact of outcome devaluation on operant behavior was evaluated after lithium chloride injections were paired with the reinforcer, or unpaired 24 hours later. After limited, but not extended instrumental training, lever pressing by groups trained under VR with 10S10E and under VI with 10S was sensitive to outcome devaluation. In contrast, responding by both the extended and limited training 10S10E VI groups was not sensitive to ethanol devaluation during the test for habitual behavior. Conclusions/Significance Operant behavior by rats trained to self-administer an ethanol-sucrose solution showed variable sensitivity to a change in the value of ethanol, with relative insensitivity developing sooner in animals that received time-variable ethanol reinforcement during training sessions. One important implication, with respect to substance abuse in humans, is that initial learning about the relationship between

  13. Consistent, high-level ethanol consumption in pig-tailed macaques via a multiple-session, limited-intake, oral self-dosing procedure.

    PubMed

    Weed, Michael R; Wilcox, Kristin M; Ator, Nancy A; Hienz, Robert D

    2008-06-01

    Alcohol abuse is a major public health burden that can lead to many adverse health effects such as impaired hepatic, gastrointestinal, central nervous system and immune system function. Preclinical animal models of alcohol abuse allow for experimental control over variables often difficult to control in human clinical studies (e.g., ethanol exposure before or during the study, history of other drug use, access to medical care, nutritional status, etc). Nonhuman primate models in particular provide increased genetic, anatomic and physiologic similarity to humans, relative to rodent models. A small percentage of macaques will spontaneously consume large quantities of ethanol; however, most nonhuman primate models of "voluntary" ethanol intake produce relatively low daily ethanol intake in the majority of monkeys. To facilitate study of chronic exposure to high levels of ethanol intake, a macaque model has been developed that induces consistent, daily high-level ethanol consumption. This multiple-session procedure employed 4 drinking sessions per day, with sessions occurring once every 6 hours. The group average alcohol consumption was 4.6 g/kg/d (SEM 0.4), roughly twice the group average consumption of previous reports. Ethanol drinking sessions produced group mean blood ethanol levels of 95 mg/dl after 60 minutes, and fine motor control was impaired up to 90 minutes after a drinking session. This model of multiple-session, limited access, oral ethanol self-dosing produced consistent, high-level ethanol consumption with each session qualifying as a "binge" drinking session using the definition of "binge" provided by the NIAAA (>80 mg/dl/session). This model of ethanol drinking in macaques will be of great utility in the study of immunological, physiological and behavioral effects of ethanol in nonhuman primates.

  14. Brain damage in a large cohort of solvent abusers.

    PubMed

    Al-Hajri, Zahra; Del Bigio, Marc R

    2010-04-01

    The neuropathology of solvent inhalation consists of patchy myelin loss with white matter macrophages that contain granular inclusions. It has been described only in a small number of cases. We sought to characterize the abnormalities in greater detail. In a retrospective study from 1995 to 2009, we encountered 88 autopsy cases with documented history of solvent abuse by inhalation and 1 with industrial exposure. Among these are 6 fetuses and infants with maternal exposure, 23 children (12-17 years), and 60 adults (18-66 years). Available brain samples from 75 cases were stained with solochrome cyanein (to demonstrate myelin) and periodic acid-Schiff (PAS) (to highlight the inclusions). Forty brains of ethanol and/or illicit drug exposed individuals and ten cases of multiple sclerosis were examined as controls. We found that 16 cases (age 23-49, median 37 years) had well-established leukoencephalopathy with multifocal myelin loss and abundant macrophages that stain with PAS and which contain birefringent inclusions. Six cases (age 15-55, median 27 years) had early leukoencephalopathy with scattered macrophages but no obvious myelin changes. Clusters of PAS-staining but non-birefringent macrophages were seen in 2/10 cases of (active) multiple sclerosis and in none of the ethanol/drug exposed brains. Ultrastructurally, inclusions from solvent cases differed from multiple sclerosis cases. Although exposure to solvents is impossible to quantify, there appears to be a duration-dependent effect. Brain damage related to solvent abuse can begin within only a few years of the onset. In the context of substance abuse, the changes are relatively specific for solvent inhalation and do not appear to result from demyelination alone. Interaction with ethanol cannot be excluded as a compounding risk factor.

  15. A pair of dopamine neurons target the D1-like dopamine receptor DopR in the central complex to promote ethanol-stimulated locomotion in Drosophila.

    PubMed

    Kong, Eric C; Woo, Katherine; Li, Haiyan; Lebestky, Tim; Mayer, Nasima; Sniffen, Melissa R; Heberlein, Ulrike; Bainton, Roland J; Hirsh, Jay; Wolf, Fred W

    2010-04-01

    Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol.

  16. Developmental Ethanol Exposure Causes Reduced Feeding and Reveals a Critical Role for Neuropeptide F in Survival

    PubMed Central

    Guevara, Amanda; Gates, Hillary; Urbina, Brianna; French, Rachael

    2018-01-01

    Food intake is necessary for survival, and natural reward circuitry has evolved to help ensure that animals ingest sufficient food to maintain development, growth, and survival. Drugs of abuse, including alcohol, co-opt the natural reward circuitry in the brain, and this is a major factor in the reinforcement of drug behaviors leading to addiction. At the junction of these two aspects of reward are alterations in feeding behavior due to alcohol consumption. In particular, developmental alcohol exposure (DAE) results in a collection of physical and neurobehavioral disorders collectively referred to as Fetal Alcohol Spectrum Disorder (FASD). The deleterious effects of DAE include intellectual disabilities and other neurobehavioral changes, including altered feeding behaviors. Here we use Drosophila melanogaster as a genetic model organism to study the effects of DAE on feeding behavior and the expression and function of Neuropeptide F. We show that addition of a defined concentration of ethanol to food leads to reduced feeding at all stages of development. Further, genetic conditions that reduce or eliminate NPF signaling combine with ethanol exposure to further reduce feeding, and the distribution of NPF is altered in the brains of ethanol-supplemented larvae. Most strikingly, we find that the vast majority of flies with a null mutation in the NPF receptor die early in larval development when reared in ethanol, and provide evidence that this lethality is due to voluntary starvation. Collectively, we find a critical role for NPF signaling in protecting against altered feeding behavior induced by developmental ethanol exposure. PMID:29623043

  17. Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation.

    PubMed

    Ren, Zhenhua; Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2016-10-01

    Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5g/kg, 25% ethanol w/v) daily for 3days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Drug Abuse

    MedlinePlus

    ... drugs, including opioids Drug abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms ...

  19. Long-lasting reductions of ethanol drinking, enhanced ethanol-induced sedation, and decreased c-fos expression in the Edinger-Westphal nucleus in Wistar rats exposed to the organophosphate chlorpyrifos.

    PubMed

    Carvajal, Francisca; López-Grancha, Matilde; Navarro, Montserrat; Sánchez-Amate, Maria del Carmen; Cubero, Inmaculada

    2007-04-01

    Intermittent or continuous exposure to a wide variety of chemically unrelated environmental pollutants might result in the development of multiple chemical intolerance and increased sensitivity to drugs of abuse. Interestingly, clinical evidence suggests that exposure to organophosphates might be linked to increased ethanol sensitivity and reduced voluntary consumption of ethanol-containing beverages in humans. The growing body of clinical and experimental evidence emerging in this new scientific field that bridges environmental health sciences, toxicology, and drug research calls for well-controlled studies aimed to analyze the nature of the neurobiological interactions of drugs and pollutants. Present study specifically evaluated neurobiological and behavioral responses to ethanol in Wistar rats that were previously exposed to the pesticide organophosphate chlorpyrifos (CPF). In agreement with clinical data, animals pretreated with a single injection of CPF showed long-lasting ethanol avoidance that was not secondary to altered gustatory processing or enhancement of the aversive properties of ethanol. Furthermore, CPF pretreatment increased ethanol-induced sedation without altering blood ethanol levels. An immunocytochemical assay revealed reduced c-fos expression in the Edinger-Westphal nucleus following CPF treatment, a critical brain area that has been implicated in ethanol intake and sedation. We hypothesize that CPF might modulate cellular mechanisms (decreased intracellular cAMP signaling, alpha-7-nicotinic receptors, and/or cerebral acetylcholinesterase inhibition) in neuronal pathways critically involved in neurobiological responses to ethanol.

  20. Ayahuasca and Its DMT- and β-carbolines - Containing Ingredients Block the Expression of Ethanol-Induced Conditioned Place Preference in Mice: Role of the Treatment Environment.

    PubMed

    Cata-Preta, Elisangela G; Serra, Yasmim A; Moreira-Junior, Eliseu da C; Reis, Henrique S; Kisaki, Natali D; Libarino-Santos, Matheus; Silva, Raiany R R; Barros-Santos, Thaísa; Santos, Lucas C; Barbosa, Paulo C R; Costa, José L; Oliveira-Lima, Alexandre J; Berro, Lais F; Marinho, Eduardo A V

    2018-01-01

    Ayahuasca is a hallucinogenic beverage produced from the decoction of Banisteriopsis caapi (Bc) and Psychotria viridis (Pv), β-carboline- and N,N -dimethyltryptamine(DMT)-containing plants, respectively. Accumulating evidence suggests that ayahuasca may have therapeutic effects on ethanol abuse. It is not known, however, whether its effects are dependent on the presence of DMT or if non-DMT-containing components would have therapeutic effects. The aim of the present study was to investigate the rewarding properties of ayahuasca (30, 100, and 300 mg/kg, orally), Bc (132, 440, and 1320 mg/kg, orally) and Pv (3.75, 12.5 and 37.5 mg/kg, i.p.) extracts and their effects on ethanol (1.8 g/kg, i.p.) reward using the conditioned place preference (CPP) paradigm in male mice. Animals were conditioned with ayahuasca, Bc or Pv extracts during 8 sessions. An intermediate, but not a high, dose of ayahuasca induced CPP in mice. Bc and Pv did not induce CPP. Subsequently, the effects of those extracts were tested on the development of ethanol-induced CPP. Ayahuasca, Bc or Pv were administered before ethanol injections during conditioning sessions. While Bc and Pv exerted no effects on ethanol-induced CPP, pretreatment with ayahuasca blocked the development of CPP to ethanol. Finally, the effects of a post-ethanol-conditioning treatment with ayahuasca, Bc or Pv on the expression of ethanol-induced CPP were tested. Animals were conditioned with ethanol, and subsequently treated with either ayahuasca, Bc or Pv in the CPP environment previously associated with saline or ethanol for 6 days. Animals were then reexposed to ethanol and ethanol-induced CPP was quantified on the following day. Treatment with all compounds in the ethanol-paired environment blocked the expression of ethanol-induced CPP. Administration of an intermediate, but not a high, dose of ayahuasca and Bc, as well as Pv administration, in the saline-paired compartment blocked the expression of ethanol-induced CPP. The

  1. Dopamine modulates acute responses to cocaine, nicotine and ethanol in Drosophila.

    PubMed

    Bainton, R J; Tsai, L T; Singh, C M; Moore, M S; Neckameyer, W S; Heberlein, U

    2000-02-24

    Drugs of abuse have a common property in mammals, which is their ability to facilitate the release of the neurotransmitter and neuromodulator dopamine in specific brain regions involved in reward and motivation. This increase in synaptic dopamine levels is believed to act as a positive reinforcer and to mediate some of the acute responses to drugs. The mechanisms by which dopamine regulates acute drug responses and addiction remain unknown. We present evidence that dopamine plays a role in the responses of Drosophila to cocaine, nicotine or ethanol. We used a startle-induced negative geotaxis assay and a locomotor tracking system to measure the effect of psychostimulants on fly behavior. Using these assays, we show that acute responses to cocaine and nicotine are blunted by pharmacologically induced reductions in dopamine levels. Cocaine and nicotine showed a high degree of synergy in their effects, which is consistent with an action through convergent pathways. In addition, we found that dopamine is involved in the acute locomotor-activating effect, but not the sedating effect, of ethanol. We show that in Drosophila, as in mammals, dopaminergic pathways play a role in modulating specific behavioral responses to cocaine, nicotine or ethanol. We therefore suggest that Drosophila can be used as a genetically tractable model system in which to study the mechanisms underlying behavioral responses to multiple drugs of abuse.

  2. Effects of ethanol on Pavlovian autoshaping in rats.

    PubMed

    Tomie, A; Cunha, C; Mosakowski, E M; Quartarolo, N M; Pohorecky, L A; Benjamin, D

    1998-09-01

    Approach responses, consummatory behaviors, and directed motor responses maintained by food reward resemble autoshaping CRs and are increased by lower doses of ethanol. This study evaluated the effects of presession i.p. injections of ethanol doses (0.00, 0.25, 0.50, 0.70. or 1.00 g/kg) on the acquisition of lever-press autoshaping CR performance in groups of male Long-Evans hooded rats. Paired groups received 15 daily sessions of Pavlovian autoshaping procedures, wherein the insertion of a retractable lever for 5 s (CS) was followed by the response-independent presentation of food (US). Ethanol facilitated lever-press autoshaping CR acquisition, as revealed by dose-related increases in the number of trials on which CRs were performed. The form of the dose-effect curve was inverted U-shaped with maximal responding induced during sessions 1-5 by the 0.70 g/kg ethanol dose. A similar dose-effect curve was observed during sessions 11-15, revealing that the effects of ethanol on autoshaping CR performance were relatively stable. A pseudoconditioning control group injected presession with 0.50 g/kg ethanol received training wherein the food US was presented randomly with respect to the lever CS. Few lever-presses were performed by the Random 0.50 group, indicating that ethanol's effects on autoshaping CR acquisition and maintenance observed in the Paired 0.50 group were not due to its psychomotor activating effects. A non-injection control group performed more autoshaping CRs than did the control group injected presession with saline, indicating that daily presession i.p. injections per se suppress autoshaping CR performance. Results reveal that low doses of ethanol enhance Pavlovian conditioning of directed motor and consummatory-like responding maintained by food reward. Implications for autoshaping accounts of impulsivity and drug abuse are considered.

  3. In vivo wireless ethanol vapor detection in the Wistar rat

    PubMed Central

    Cheney, C. Parks; Srijanto, B.; Hedden, D. L.; Gehl, A.; Ferrell, T. L.; Schultz, J.; Engleman, E. A.; McBride, W. J.; O'Connor, S.

    2009-01-01

    Traditional alcohol studies measure blood alcohol concentration to elucidate the biomedical factors that contribute to alcohol abuse and alcoholism. These measurements require large and expensive equipment, are labor intensive, and are disruptive to the subject. To alleviate these problems, we have developed an implantable, wireless biosensor that is capable of measuring alcohol levels for up to six weeks. Ethanol levels were measured in vivo in the interstitial fluid of a Wistar rat after administering 1 g/kg and 2 g/kg ethanol by intraperitoneal (IP) injection. The data were transmitted wirelessly using a biosensor selective for alcohol detection. A low-power piezoresistive microcantilever sensor array was used with a polymer coating suitable for measuring ethanol concentrations at 100% humidity over several hours. A hydrophobic, vapor permeable nanopore membrane was used to screen liquid and ions while allowing vapor to pass to the sensor from the subcutaneous interstitial fluid. PMID:20161283

  4. Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation

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

    Ren, Zhenhua

    Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanolmore » by gavage (5 g/kg, 25% ethanol w/v) daily for 3 days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3 days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas. - Highlights: • Chronic plus binge alcohol drinking causes more pancreatic injury. • Chronic plus binge alcohol drinking induces more pancreatic inflammation. • Chronic plus binge alcohol causes more endoplasmic reticulum stress and oxidative stress.« less

  5. The propensity for consuming ethanol in Drosophila requires rutabaga adenylyl cyclase expression within mushroom body neurons

    PubMed Central

    Xu, Shiyu; Chan, Tammy; Shah, Vruntant; Zhang, Shixing; Pletcher, Scott D.; Roman, Gregg

    2012-01-01

    Alcohol activates reward systems through an unknown mechanism, in some cases leading to alcohol abuse and dependence. Herein, we utilized a two-choice Capillary Feeding assay to address the neural and molecular basis for ethanol self-administration in Drosophila melanogaster. Wild-type Drosophila demonstrates a significant preference for food containing between 5 and 15% ethanol. Preferred ethanol self-administration does not appear to be due to caloric advantage, nor due to perceptual biases, suggesting a hedonic bias for ethanol exists in Drosophila. Interestingly, rutabaga adenylyl cyclase expression within intrinsic mushroom body neurons is necessary for robust ethanol self-administration. The expression of rutabaga in mushroom bodies is also required for both appetitive and aversive olfactory associative memories, suggesting that reinforced behavior has an important role in the ethanol self-administration in Drosophila. However, rutabaga expression is required more broadly within the mushroom bodies for the preference for ethanol-containing food than for olfactory memories reinforced by sugar reward. Together these data implicate cAMP signaling and behavioral reinforcement for preferred ethanol self-administration in Drosophila melanogaster. PMID:22624869

  6. Junk food diet-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking.

    PubMed

    Cook, Jason B; Hendrickson, Linzy M; Garwood, Grant M; Toungate, Kelsey M; Nania, Christina V; Morikawa, Hitoshi

    2017-01-01

    Similar to drugs of abuse, the hedonic value of food is mediated, at least in part, by the mesostriatal dopamine (DA) system. Prolonged intake of either high calorie diets or drugs of abuse both lead to a blunting of the DA system. Most studies have focused on DAergic alterations in the striatum, but little is known about the effects of high calorie diets on ventral tegmental area (VTA) DA neurons. Since high calorie diets produce addictive-like DAergic adaptations, it is possible these diets may increase addiction susceptibility. However, high calorie diets consistently reduce psychostimulant intake and conditioned place preference in rodents. In contrast, high calorie diets can increase or decrease ethanol drinking, but it is not known how a junk food diet (cafeteria diet) affects ethanol drinking. In the current study, we administered a cafeteria diet consisting of bacon, potato chips, cheesecake, cookies, breakfast cereals, marshmallows, and chocolate candies to male Wistar rats for 3-4 weeks, producing an obese phenotype. Prior cafeteria diet feeding reduced homecage ethanol drinking over 2 weeks of testing, and transiently reduced sucrose and chow intake. Importantly, cafeteria diet had no effect on ethanol metabolism rate or blood ethanol concentrations following 2g/kg ethanol administration. In midbrain slices, we showed that cafeteria diet feeding enhances DA D2 receptor (D2R) autoinhibition in VTA DA neurons. These results show that junk food diet-induced obesity reduces ethanol drinking, and suggest that increased D2R autoinhibition in the VTA may contribute to deficits in DAergic signaling and reward hypofunction observed with obesity.

  7. GABA(A) receptor modulation during adolescence alters adult ethanol intake and preference in rats.

    PubMed

    Hulin, Mary W; Amato, Russell J; Winsauer, Peter J

    2012-02-01

    To address the hypothesis that GABA(A) receptor modulation during adolescence may alter the abuse liability of ethanol during adulthood, the effects of adolescent administration of both a positive and negative GABA(A) receptor modulator on adult alcohol intake and preference were assessed. Three groups of adolescent male rats received 12 injections of lorazepam (3.2 mg/kg), dehydroepiandrosterone (DHEA, 56 mg/kg), or vehicle on alternate days starting on postnatal day (PD) 35. After this time, the doses were increased to 5.6 and 100 mg/kg, respectively, for 3 more injections on alternate days. Subjects had access to 25 to 30 g of food daily, during the period of the first 6 injections, and 18 to 20 g thereafter. Food intake of each group was measured 60 minutes after food presentation, which occurred immediately after drug administration on injection days or at the same time of day on noninjection days. When subjects reached adulthood (PD 88), ethanol preference was determined on 2 separate occasions, an initial 3-day period and a 12-day period, in which increasing concentrations of ethanol were presented. During each preference test, intake of water, saccharin, and an ethanol/saccharin solution was measured after each 23-hour access period. During adolescence, lorazepam increased 60-minute food intake, and this effect was enhanced under the more restrictive feeding schedule. DHEA had the opposite effect on injection days, decreasing food intake compared with noninjection days. In adulthood, the lorazepam-treated group preferred the 2 lowest concentrations of ethanol/saccharin more than saccharin alone compared with vehicle-treated subjects, which showed no preference for any concentration of ethanol/saccharin over saccharin. DHEA-treated subjects showed no preference among the 3 solutions. These data demonstrate that GABA(A) receptor modulation during adolescence can alter intake and preference for ethanol in adulthood and highlights the importance of drug history

  8. Ethanol activates Midkine and Anaplastic lymphoma kinase signaling in neuroblastoma cells and in the brain

    PubMed Central

    He, Donghong; Chen, Hu; Muramatsu, Hisako; Lasek, Amy W.

    2015-01-01

    Alcohol engages signaling pathways in the brain. Midkine (MDK) is a neurotrophic factor that is overexpressed in the prefrontal cortex of alcoholics. MDK and one of its receptors, anaplastic lymphoma kinase (ALK), also regulate behavioral responses to ethanol in mice. The goal of this study was to determine whether MDK and ALK expression and signaling are activated by ethanol. We found that ethanol treatment of neuroblastoma cells increased MDK and ALK expression. We also assessed activation of ALK by ethanol in cells and found that ALK and ALK-dependent extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3) phosphorylation increased rapidly with ethanol exposure. Similarly, treatment of cells with recombinant MDK protein increased ALK, ERK and STAT3 phosphorylation, suggesting that ethanol may utilize MDK to activate ALK signaling. In support of this, transfection of cells with MDK siRNAs attenuated ALK signaling in response to ethanol. Ethanol also activates ERK signaling in the brain. We found that inhibition of ALK or knockout of MDK attenuated ethanol-induced ERK phosphorylation in mouse amygdala. These results demonstrate that ethanol engages MDK and ALK signaling, which has important consequences for alcohol-induced neurotoxicity and the regulation of behaviors related to alcohol abuse. PMID:26206265

  9. Consumption of Substances of Abuse during Pregnancy Increases Consumption in Offspring: Possible Underlying Mechanisms

    PubMed Central

    Poon, Kinning; Leibowitz, Sarah F.

    2016-01-01

    Correlative human observational studies on substances of abuse have been highly dependent on the use of rodent models to determine the neuronal and molecular mechanisms that control behavioral outcomes. This is particularly true for gestational exposure to non-illicit substances of abuse, such as excessive dietary fat, ethanol, and nicotine, which are commonly consumed in our society. Exposure to these substances during the prenatal period has been shown in offspring to increase their intake of these substances, induce other behavioral changes, and affect neurochemical systems in several brain areas that are known to control behavior. More importantly, emerging studies are linking the function of the immune system to these neurochemicals and ingestion of these abused substances. This review article will summarize the prenatal rodent models used to study developmental changes in offspring caused by prenatal exposure to dietary fat, ethanol, or nicotine. We will discuss the various techniques used for the administration of these substances into rodents and summarize the published outcomes induced by prenatal exposure to these substances. Finally, this review will cover some of the recent evidence for the role of immune factors in causing these behavioral and neuronal changes. PMID:27148536

  10. Child Sexual Abuse

    MedlinePlus

    Sexual abuse is one form of child abuse. It includes a wide range of actions between a child ... to children or pressuring them for sex is sexual abuse. Using a child for pornography is also sexual ...

  11. Ethanol-related behaviors in mice lacking the sigma-1 receptor.

    PubMed

    Valenza, Marta; DiLeo, Alyssa; Steardo, Luca; Cottone, Pietro; Sabino, Valentina

    2016-01-15

    The Sigma-1 receptor (Sig-1R) is a chaperone protein that has been implicated in drug abuse and addiction. Multiple studies have characterized the role the Sig-1R plays in psychostimulant addiction; however, fewer studies have specifically investigated its role in alcohol addiction. We have previously shown that antagonism of the Sig-1R reduces excessive drinking and motivation to drink, whereas agonism induces binge-like drinking in rodents. The objectives of these studies were to investigate the impact of Sig-1R gene deletion in C57Bl/6J mice on ethanol drinking and other ethanol-related behaviors. We used an extensive panel of behavioral tests to examine ethanol actions in male, adult mice lacking Oprs1, the gene encoding the Sig-1R. To compare ethanol drinking behavior, Sig-1 knockout (KO) and wild type (WT) mice were subject to a two-bottle choice, continuous access paradigm with different concentrations of ethanol (3-20% v/v) vs. water. Consumption of sweet and bitter solutions was also assessed in Sig-1R KO and WT mice. Finally, motor stimulant sensitivity, taste aversion and ataxic effects of ethanol were assessed. Sig-1R KO mice displayed higher ethanol intake compared to WT mice; the two genotypes did not differ in their sweet or bitter taste perception. Sig-1R KO mice showed lower sensitivity to ethanol stimulant effects, but greater sensitivity to its taste aversive effects. Ethanol-induced sedation was instead unaltered in the mutants. Our results prove that the deletion of the Sig-1R increases ethanol consumption, likely by decreasing its rewarding effects, and therefore indicating that the Sig-1R is involved in modulation of the reinforcing effects of alcohol. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Ethanol-related behaviors in mice lacking the sigma-1 receptor

    PubMed Central

    Valenza, Marta; DiLeo, Alyssa; Steardo, Luca; Cottone, Pietro; Sabino, Valentina

    2015-01-01

    Rationale The Sigma-1 receptor (Sig-1R) is a chaperone protein that has been implicated in drug abuse and addiction. Multiple studies have characterized the role the Sig-1R plays in psychostimulants addiction, but fewer studies have specifically investigated its role in alcohol addiction. We have previously shown that antagonism of the Sig-1R reduces excessive drinking and motivation to drink, whereas agonism induces binge-like drinking in rodents. Objectives The objectives of these studies were to investigate the impact of Sig-1R gene deletion in C57Bl/6J mice on ethanol drinking and other ethanol-related behaviors. Methods We used an extensive panel of behavioral tests to examine ethanol actions in male, adult mice lacking Oprs1, the gene encoding the Sig-1R. To compare ethanol drinking behavior, Sig-1 knockout (KO) and wild type (WT) mice were subject to a two-bottle choice, continuous access paradigm with different concentrations of ethanol (3%–20% v/v) vs. water. Consumption of sweet and bitter solutions was also assessed in Sig-1R KO and WT mice. Finally, motor stimulant sensitivity, taste aversion and ataxic effects of ethanol were assessed. Results Sig-1R KO mice displayed higher ethanol intake compared to WT mice; the two genotypes did not differ in their sweet or bitter taste perception. Sig-1R KO mice showed lower sensitivity to ethanol stimulant effects, but greater sensitivity to its taste aversive effects. Ethanol-induced sedation was unaltered in the mutants. Conclusions Our results suggest that the deletion of the Sig-1R increases ethanol consumption, likely by decreasing its rewarding effects, and therefore indicating that the Sig-1R is involved in modulation of the reinforcing effects of alcohol. PMID:26462569

  13. Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes

    PubMed Central

    Oppermann, Elsie; Jobin, Christian; Schleucher, Elke; Marzi, Ingo

    2014-01-01

    Chronic ethanol abuse is known to increase susceptibility to infections after injury, in part, by modification of macrophage function. Several intracellular signalling mechanisms are involved in the initiation of inflammatory responses, including the nuclear factor-κB (NF-κB) pathway. In this study, we investigated the systemic and hepatic effect of chronic ethanol feeding on in vivo activation of NF-κB in NF-κBEGFP reporter gene mice. Specifically, the study focused on Kupffer cell proinflammatory cytokines IL-6 and TNF-α and activation of NF-κB after chronic ethanol feeding followed by in vitro stimulation with lipopolysaccharide (LPS). We found that chronic ethanol upregulated NF-κB activation and increased hepatic and systemic proinflammatory cytokine levels. Similarly, LPS-stimulated IL-1β release from whole blood was significantly enhanced in ethanol-fed mice. However, LPS significantly increased IL-6 and TNF-α levels. These results demonstrate that chronic ethanol feeding can improve the responsiveness of macrophage LPS-stimulated IL-6 and TNF-α production and indicate that this effect may result from ethanol-induced alterations in intracellular signalling through NF-κB. Furthermore, LPS and TNF-α stimulated the gene expression of different inflammatory mediators, in part, in a NF-κB-dependent manner. PMID:24623963

  14. Magnetic resonance imaging findings in substance abuse: alcohol and alcoholism and syndromes associated with alcohol abuse.

    PubMed

    Spampinato, M Vittoria; Castillo, Mauricio; Rojas, Rafael; Palacios, Enrique; Frascheri, Laura; Descartes, Fernando

    2005-06-01

    Alcohol abuse is common among the population and results in significant diseases that shorten life span. Ethanol may result in chronic brain changes such as atrophy but may also result in neurologic disease that may be acute or chronic and sometimes life threatening. Accompanying vitamin deficiencies may lead to Wernicke's encephalopathy and changes in serum osmosis may lead to several acute demyelinating disorders. In addition, pregnant women who consume alcohol place their babies at high risk for the fetal alcohol syndrome. In this article we review these disorders and emphasize their imaging features.

  15. Child Sexual Abuse

    MedlinePlus

    ... No child is prepared to cope with repeated sexual stimulation. Even a two or three year old, who ... abuse. Some signs can only be detected on physical exam by a physician. Sexual abuse can also include noncontact abuse, such as ...

  16. Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to {delta}{sup 9}-tetrahydrocannabinol

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

    Economidou, Daina; Mattioli, Laura; Ubaldi, Massimo

    The present study evaluated the consequences of perinatal {delta}{sup 9}-tetrahydrocannabinol ({delta}{sup 9}-THC) treatment (5 mg/kg/day by gavage), either alone or combined with ethanol (3% v/v as the only fluid available), on ethanol self-administration and alcohol-seeking behavior in rat adult offspring. Furthermore, the effect of the selective cannabinoid CB{sub 1} receptor antagonist, SR-141716A, on ethanol self-administration and on reinstatement of ethanol-seeking behavior induced either by stress or conditioned drug-paired cues was evaluated in adult offspring of rats exposed to the same perinatal treatment. Lastly, microarray experiments were conducted to evaluate if perinatal treatment with {delta}{sup 9}-tetrahydrocannabinol, ethanol or their combination causesmore » long-term changes in brain gene expression profile in rats. The results of microarray data analysis showed that 139, 112 and 170 genes were differentially expressed in the EtOH, {delta}{sup 9}-THC, or EtOH + {delta}{sup 9}-THC group, respectively. No differences in alcohol self-administration and alcohol seeking were observed between rat groups. Intraperitoneal (IP) administration of SR-141716A (0.3-3.0 mg/kg) significantly reduced lever pressing for ethanol and blocked conditioned reinstatement of alcohol seeking. At the same doses SR-141716A failed to block foot-shock stress-induced reinstatement of alcohol seeking. The results reveal that perinatal exposure to {delta}{sup 9}-THC ethanol or their combination results in evident changes in gene expression patterns. However, these treatments do not significantly affect vulnerability to ethanol abuse in adult offspring. On the other hand, the results obtained with SR-141716A emphasize that endocannabinoid mechanisms play a major role in ethanol self-administration, as well as in the reinstatement of ethanol-seeking behavior induced by conditioned cues, supporting the idea that cannabinoid CB{sub 1} receptor antagonists may represent

  17. Evidence that Melanocortin Receptor Agonist Melanotan-II Synergistically Augments the Ability of Naltrexone to Blunt Binge-Like Ethanol Intake in Male C57BL/6J Mice

    PubMed Central

    Navarro, Montserrat; Carvajal, Francisca; Lerma-Cabrera, Jose Manuel; Cubero, Inmaculada; Picker, Mitchell J.; Thiele, Todd E.

    2015-01-01

    Background The non-selective opioid receptor antagonist, naltrexone (NAL), reduces alcohol (ethanol) consumption in animals and humans and is an approved medication for treating alcohol abuse disorders. Proopiomelanocortin (POMC)-derived melanocortin (MC) and opioid peptides are produced in the same neurons in the brain, and recent pre-clinical evidence shows that MC receptor (MCR) agonists reduce excessive ethanol drinking in animal models. Interestingly, there is a growing body of literature revealing interactions between the MC and opioid systems in the modulation of pain, drug tolerance, and food intake. Method In the present report, a mouse model of binge ethanol drinking was employed to determine if the MCR agonist, melanotan-II (MTII), would improve the effectiveness of NAL in reducing excessive binge-like ethanol drinking when these drugs were co-administered prior to ethanol access. Results Both NAL and MTII blunt binge-like ethanol drinking and associated blood ethanol levels, and when administered together, a low dose of MTII (0.26 mg/kg) produces a 7.6-fold increase in the effectiveness of NAL in reducing binge-like ethanol drinking. Using isobolographic analysis, it is demonstrated that MTII increases the effectiveness of NAL in a synergistic manner. Conclusions The current observations suggest that activators of MC signaling may represent a new approach to treating alcohol abuse disorders, and a way to potentially improve existing NAL-based therapies. PMID:26108334

  18. Substance Abuse. Policy Statement.

    ERIC Educational Resources Information Center

    National Collaboration for Youth, Washington, DC.

    This paper presents the policy statement on substance abuse from the National Collaboration for Youth (NCY). The policy statement section lists programs and activities supported by the NCY. A section on background includes a statement of the issue of substance abuse. Areas examined in this section include alcohol abuse and drunk driving among…

  19. Context-dependent effects of rimonabant on ethanol-induced conditioned place preference in female mice.

    PubMed

    Silva, Aline A F; Barbosa-Souza, Evelyn; Confessor-Carvalho, Cassio; Silva, Raiany R R; De Brito, Ana Carolina L; Cata-Preta, Elisangela G; Silva Oliveira, Thaynara; Berro, Lais F; Oliveira-Lima, Alexandre J; Marinho, Eduardo A V

    2017-10-01

    The CB1 receptor antagonist rimonabant has been previously found to prevent behavioral effects of drugs of abuse in a context-dependent manner, suggesting an important role of endocannabinoid signaling in drug-induced environmental conditioning. The aim of the present study was to evaluate the effects of rimonabant on ethanol-induced conditioned place preference (CPP) in female mice. Animals were conditioned with saline or ethanol (1.8g/kg) during 8 sessions, and subsequently treated with either saline or rimonabant (1 or 10mg/kg) in the CPP environment previously associated with saline (unpaired) or ethanol (paired) for 6 consecutive days. Animals were then challenged with ethanol (1.8g/kg) in the ethanol-paired environment and ethanol-induced CPP was quantified on the following day. While treatment with 1mg/kg rimonabant in the saline-associated environment had no effects on the subsequent expression of ethanol-induced CPP, it blocked the expression of CPP to ethanol when paired to the ethanol-associated environment. When given in the ethanol-paired environment, 10mg/kg rimonabant induced aversion to the ethanol-associated environment. The same aversion effect was observed for 10mg/kg rimonabant when given in the saline-associated environment, thereby potentiating the expression of ethanol-induced CPP. Importantly, rimonabant did not induce CPP or conditioned place aversion on its own. Controlling for the estrous cycle phase showed no influences of hormonal cycle on the development and expression of ethanol-induced CPP. Our data suggest that rimonabant reduces the rewarding properties of ethanol by abolishing drug-environment conditioning in the CPP paradigm in a context-dependent manner. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Chronic tolerance to ethanol-induced sedation: implication for age-related differences in locomotor sensitization.

    PubMed

    Quoilin, Caroline; Didone, Vincent; Tirelli, Ezio; Quertemont, Etienne

    2013-06-01

    The adolescent brain has been suggested to be particularly sensitive to ethanol-induced neuroadaptations, which in turn could increase the risk of youths for alcohol abuse and dependence. Sensitization to the locomotor stimulant effects of ethanol has often been used as an animal model of ethanol-induced neuroadaptations. Previously, we showed that young mice were more sensitive than adults to the locomotor sensitization induced by high ethanol doses. However, this effect could be due to age-related differences in chronic tolerance to the sedative effects of ethanol. The aim of the present study is to assess chronic tolerance to the sedative effects of ethanol in weaning 21-day-old (P21), adolescent 35-day-old (P35) and adult 63-day-old (P63) female Swiss mice. After a daily injection of saline or 4 g/kg ethanol during 6 consecutive days, all P21, P35 and P63 mice were injected with 4 g/kg ethanol and submitted to the loss of righting reflex procedure. Our results confirm that the sensitivity to the acute sedative effects of ethanol gradually increases with age. Although this schedule of ethanol injections induces significant age-related differences in ethanol sensitization, it did not reveal significant differences between P21, P35 and P63 mice in the development of a chronic ethanol tolerance to its sedative effects. The present results show that age-related differences in the development of ethanol sensitization cannot be explained by differences in chronic ethanol tolerance to its sedative effects. More broadly, they do not support the idea that ethanol-induced sensitization is a by-product of chronic ethanol tolerance. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Chronic Intermittent Ethanol Exposure Enhances the Excitability and Synaptic Plasticity of Lateral Orbitofrontal Cortex Neurons and Induces a Tolerance to the Acute Inhibitory Actions of Ethanol

    PubMed Central

    Nimitvilai, Sudarat; Lopez, Marcelo F; Mulholland, Patrick J; Woodward, John J

    2016-01-01

    Alcoholism is associated with changes in brain reward and control systems, including the prefrontal cortex. In prefrontal areas, the orbitofrontal cortex (OFC) has been suggested to have an important role in the development of alcohol-abuse disorders and studies from this laboratory demonstrate that OFC-mediated behaviors are impaired in alcohol-dependent animals. However, it is not known whether chronic alcohol (ethanol) exposure alters the fundamental properties of OFC neurons. In this study, mice were exposed to repeated cycles of chronic intermittent ethanol (CIE) exposure to induce dependence and whole-cell patch-clamp electrophysiology was used to examine the effects of CIE treatment on lateral OFC (lOFC) neuron excitability, synaptic transmission, and plasticity. Repeated cycles of CIE exposure and withdrawal enhanced current-evoked action potential (AP) spiking and this was accompanied by a reduction in the after-hyperpolarization and a decrease in the functional activity of SK channels. CIE mice also showed an increase in the AMPA/NMDA ratio, and this was associated with an increase in GluA1/GluA2 AMPA receptor expression and a decrease in GluN2B NMDA receptor subunits. Following CIE treatment, lOFC neurons displayed a persistent long-term potentiation of glutamatergic synaptic transmission following a spike-timing-dependent protocol. Lastly, CIE treatment diminished the inhibitory effect of acute ethanol on AP spiking of lOFC neurons and reduced expression of the GlyT1 transporter. Taken together, these results suggest that chronic exposure to ethanol leads to enhanced intrinsic excitability and glutamatergic synaptic signaling of lOFC neurons. These alterations may contribute to the impairment of OFC-dependent behaviors in alcohol-dependent individuals. PMID:26286839

  2. Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

    PubMed Central

    Bull, Cecilia; Freitas, Kelen CC; Zou, Shiping; Poland, Ryan S; Syed, Wahab A; Urban, Daniel J; Minter, Sabrina C; Shelton, Keith L; Hauser, Kurt F; Negus, S Stevens; Knapp, Pamela E; Bowers, M Scott

    2014-01-01

    Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with

  3. Rat nucleus accumbens core astrocytes modulate reward and the motivation to self-administer ethanol after abstinence.

    PubMed

    Bull, Cecilia; Freitas, Kelen C C; Zou, Shiping; Poland, Ryan S; Syed, Wahab A; Urban, Daniel J; Minter, Sabrina C; Shelton, Keith L; Hauser, Kurt F; Negus, S Stevens; Knapp, Pamela E; Bowers, M Scott

    2014-11-01

    Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with

  4. Effect of drugs of abuse on social behaviour: a review of animal models.

    PubMed

    Blanco-Gandía, Maria C; Mateos-García, Ana; García-Pardo, Maria P; Montagud-Romero, Sandra; Rodríguez-Arias, Marta; Miñarro, José; Aguilar, María A

    2015-09-01

    Social behaviour is disturbed in many substance abuse and psychiatric disorders. Given the consensus that social behaviours of lower mammals may help to understand some human emotional reactions, the aim of the present work was to provide an up-to-date review of studies on the changes in social behaviour induced by drugs of abuse. Various animal models have been used to study the relationship between drugs of abuse and social behaviour. Herein, we describe the effects of different substances of abuse on the three most commonly used animal models of social behaviour: the social play test, the social interaction test and the resident-intruder paradigm. The first is the most widely used test to assess adolescent behaviour in rodents, the second is generally used to evaluate a wide repertoire of behaviours in adulthood and the latter is specific to aggressive behaviour. Throughout the review we will explore the most relevant studies carried out to date to evaluate the effects of alcohol, cocaine, opioids, 3,4-methylenedioxymethamphetamine (MDMA), cannabinoids, nicotine and other drugs of abuse on these three paradigms, taking into account the influence of different variables, such as social history, age and type of exposure. Drugs of diverse pharmacological classes induce alterations in social behaviour, although they can be contrasting depending on several factors (drug, individual differences and environmental conditions). Ethanol and nicotine increase social interaction at low doses but reduce it at high doses. Psychostimulants, MDMA and cannabinoids reduce social interaction, whereas opiates increase it. Ethanol and psychostimulants enhance aggression, whereas MDMA, opiates, cannabinoids and nicotine reduce it. Prenatal drug exposure alters social behaviour, whereas drug withdrawal decreases sociability and enhances aggression. As a whole, this evidence has improved our understanding of the social dimension of drug addiction.

  5. Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet

    PubMed Central

    Karatayev, Olga; Lukatskaya, Olga; Moon, Sang-Ho; Guo, Wei-Ran; Chen, Dan; Algava, Diane; Abedi, Susan; Leibowitz, Sarah F.

    2015-01-01

    Clinical studies demonstrate frequent co-existence of nicotine and alcohol abuse and suggest that this may result, in part, from the ready access to and intake of fat-rich diets. Whereas animal studies show that high-fat diet intake in adults can enhance the consumption of either nicotine or ethanol and that maternal consumption of a fat-rich diet during pregnancy increases operant responding for nicotine in offspring, little is known about the impact of dietary fat on the co-abuse of these two drugs. The goal of this study was to test in Long-Evans rats the effects of perinatal exposure to fat on the co-use of nicotine and ethanol, using a novel paradigm that involves simultaneous intravenous (IV) self-administration of these two drugs. Fat- vs. chow-exposed offspring were characterized and compared, first in terms of their nicotine self-administration behavior, then in terms of their nicotine/ethanol self-administration behavior, and lastly in terms of their self-administration of ethanol in the absence of nicotine. The results demonstrate that maternal consumption of fat compared to low-fat chow during gestation and lactation significantly stimulates nicotine self-administration during fixed-ratio testing. It also increases nicotine/ethanol self-administration during fixed-ratio and dose-response testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint during progressive ratio testing. Of particular note is the finding that rats perinatally exposed to fat self-administer significantly more of the nicotine/ethanol mixture as compared to nicotine alone, an effect not evident in the chow-control rats. After removal of nicotine from the nicotine/ethanol mixture, this difference between the fat- and chow-exposed rats was lost, with both groups failing to acquire the self-administration of ethanol alone. Together, these findings suggest that perinatal exposure to a fat-rich diet, in addition to stimulating self-administration of nicotine, causes

  6. Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet.

    PubMed

    Karatayev, Olga; Lukatskaya, Olga; Moon, Sang-Ho; Guo, Wei-Ran; Chen, Dan; Algava, Diane; Abedi, Susan; Leibowitz, Sarah F

    2015-08-01

    Clinical studies demonstrate frequent co-existence of nicotine and alcohol abuse and suggest that this may result, in part, from the ready access to and intake of fat-rich diets. Whereas animal studies show that high-fat diet intake in adults can enhance the consumption of either nicotine or ethanol and that maternal consumption of a fat-rich diet during pregnancy increases operant responding for nicotine in offspring, little is known about the impact of dietary fat on the co-abuse of these two drugs. The goal of this study was to test in Long-Evans rats the effects of perinatal exposure to fat on the co-use of nicotine and ethanol, using a novel paradigm that involves simultaneous intravenous (IV) self-administration of these two drugs. Fat- vs. chow-exposed offspring were characterized and compared, first in terms of their nicotine self-administration behavior, then in terms of their nicotine/ethanol self-administration behavior, and lastly in terms of their self-administration of ethanol in the absence of nicotine. The results demonstrate that maternal consumption of fat compared to low-fat chow during gestation and lactation significantly stimulates nicotine self-administration during fixed-ratio testing. It also increases nicotine/ethanol self-administration during fixed-ratio and dose-response testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint during progressive ratio testing. Of particular note is the finding that rats perinatally exposed to fat self-administer significantly more of the nicotine/ethanol mixture as compared to nicotine alone, an effect not evident in the chow-control rats. After removal of nicotine from the nicotine/ethanol mixture, this difference between the fat- and chow-exposed rats was lost, with both groups failing to acquire the self-administration of ethanol alone. Together, these findings suggest that perinatal exposure to a fat-rich diet, in addition to stimulating self-administration of nicotine, causes

  7. Actions of Acute and Chronic Ethanol on Presynaptic Terminals

    PubMed Central

    Roberto, Marisa; Treistman, Steven N.; Pietrzykowski, Andrzej Z.; Weiner, Jeff; Galindo, Rafael; Mameli, Manuel; Valenzuela, Fernando; Zhu, Ping Jun; Lovinger, David; Zhang, Tao A.; Hendricson, Adam H.; Morrisett, Richard; Siggins, George Robert

    2014-01-01

    This article presents the proceedings of a symposium entitled “The Tipsy Terminal: Presynaptic Effects of Ethanol” (held at the annual meeting of the Research Society on Alcoholism, in Santa Barbara, CA, June 27, 2005). The objective of this symposium was to focus on a cellular site of ethanol action underrepresented in the alcohol literature, but quickly becoming a “hot” topic. The chairs of the session were Marisa Roberto and George Robert Siggins. Our speakers were chosen on the basis of the diverse electrophysiological and other methods used to discern the effects of acute and chronic ethanol on presynaptic terminals and on the basis of significant insights that their data provide for understanding ethanol actions on neurons in general, as mechanisms underlying problematic behavioral effects of alcohol. The 5 presenters drew from their recent studies examining the effects of acute and chronic ethanol using a range of sophisticated methods from electrophysiological analysis of paired-pulse facilitation and spontaneous and miniature synaptic currents (Drs. Weiner, Valenzuela, Zhu, and Morrisett), to direct recording of ion channel activity and peptide release from acutely isolated synaptic terminals (Dr. Treistman), to direct microscopic observation of vesicular release (Dr. Morrisett). They showed that ethanol administration could both increase and decrease the probability of release of different transmitters from synaptic terminals. The effects of ethanol on synaptic terminals could often be correlated with important behavioral or developmental actions of alcohol. These and other novel findings suggest that future analyses of synaptic effects of ethanol should attempt to ascertain, in multiple brain regions, the role of presynaptic terminals, relevant presynaptic receptors and signal transduction linkages, exocytotic mechanisms, and their involvement in alcohol’s behavioral actions. Such studies could lead to new treatment strategies for alcohol

  8. Dependence-induced ethanol drinking and GABA neurotransmission are altered in Alk deficient mice

    PubMed Central

    Schweitzer, Paul; Cates-Gatto, Chelsea; Varodayan, Florence P.; Nadav, Tali; Roberto, Marisa; Lasek, Amy W.; Roberts, Amanda J.

    2016-01-01

    Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the brain and implicated in alcohol abuse in humans and behavioral responses to ethanol in mice. Previous studies have shown an association of human ALK with acute responses to alcohol and alcohol dependence. In addition, Alk knockout (Alk −/−) mice consume more ethanol in a binge-drinking test and show increased sensitivity to ethanol sedation. However, the function of ALK in excessive drinking following the establishment of ethanol dependence has not been examined. In this study, we tested Alk −/− mice for dependence-induced drinking using the chronic intermittent ethanol-two bottle choice drinking (CIE-2BC) protocol. We found that Alk −/− mice initially consume more ethanol prior to CIE exposure, but do not escalate ethanol consumption after exposure, suggesting that ALK may promote the escalation of drinking after ethanol dependence. To determine the mechanism(s) responsible for this behavioral phenotype we used an electrophysiological approach to examine GABA neurotransmission in the central nucleus of the amygdala (CeA), a brain region that regulates alcohol consumption and shows increased GABA signaling after chronic ethanol exposure. GABA transmission in ethanol-naïve Alk −/− mice was enhanced at baseline and potentiated in response to acute ethanol application when compared to wild-type (Alk +/+) mice. Moreover, basal GABA transmission was not elevated by CIE exposure in Alk −/− mice as it was in Alk +/+ mice. These data suggest that ALK plays a role in dependence-induced drinking and the regulation of presynaptic GABA release in the CeA. PMID:26946429

  9. Transgenic over expression of nicotinic receptor alpha 5, alpha 3, and beta 4 subunit genes reduces ethanol intake in mice.

    PubMed

    Gallego, Xavier; Ruiz-Medina, Jessica; Valverde, Olga; Molas, Susanna; Robles, Noemí; Sabrià, Josefa; Crabbe, John C; Dierssen, Mara

    2012-05-01

    Abuse of alcohol and smoking are extensively co-morbid. Some studies suggest partial commonality of action of alcohol and nicotine mediated through nicotinic acetylcholine receptors (nAChRs). We tested mice with transgenic over expression of the alpha 5, alpha 3, beta 4 receptor subunit genes, which lie in a cluster on human chromosome 15, that were previously shown to have increased nicotine self-administration, for several responses to ethanol. Transgenic and wild-type mice did not differ in sensitivity to several acute behavioral responses to ethanol. However, transgenic mice drank less ethanol than wild-type in a two-bottle (ethanol vs. water) preference test. These results suggest a complex role for this receptor subunit gene cluster in the modulation of ethanol's as well as nicotine's effects. Copyright © 2012. Published by Elsevier Inc.

  10. Effects of Ethanol on Brain Extracellular Matrix: Implications for Alcohol Use Disorder

    PubMed Central

    Lasek, Amy W.

    2016-01-01

    The brain extracellular matrix (ECM) occupies the space between cells and is involved in cell-matrix and cell-cell adhesion. However, in addition to providing structural support to brain tissue, the ECM activates cell signaling and controls synaptic transmission. The expression and activity of brain ECM components are regulated by alcohol exposure. This review will discuss what is currently known about the effects of alcohol on the activity and expression of brain ECM components. An interpretation of how these changes might promote alcohol use disorder (AUD) will be also provided. Ethanol exposure decreases levels of structural proteins involved in the interstitial matrix and basement membrane, with a concomitant increase in proteolytic enzymes that degrade these components. In contrast, ethanol exposure generally increases perineuronal net (PN) components. Because the ECM has been shown to regulate both synaptic plasticity and behavioral responses to drugs of abuse, regulation of the brain ECM by alcohol may be relevant to the development of alcoholism. Although investigation of the function of brain ECM in alcohol abuse is still in early stages, a greater understanding of the interplay between ECM and alcohol might lead to novel therapeutic strategies for treating AUD. PMID:27581478

  11. Mimics of child abuse: Can choking explain abusive head trauma?

    PubMed

    Edwards, George A

    2015-10-01

    Choking is one of the alternative explanations of abusive head trauma in children that have been offered in courtroom testimony and in the media. Most of these explanations - including choking - are not scientifically supported. This article highlights four points. (1) The origins of choking as an explanation for intracranial and retinal hemorrhages are speculative. (2) Choking has been used in high profile court testimony as an explanation for the death of a child thought to have been abused. (3) A case report that proposes choking as an alternative explanation for the death of a child diagnosed with abusive head trauma includes omissions and misrepresentations of facts. (4) There was a decision by the editor of the journal that published the case report that it was not necessary to include all the facts of the case; moreover, the editor indicated that facts are not required when presenting an alternative explanation. The use of scientifically unsupported alternative explanations for abusive head trauma based on inaccurate and biased information constitutes further victimization of the abused child and represents a travesty of justice. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  12. Alcohol abuse as a risk factor for and consequence of child abuse.

    PubMed

    Widom, C S; Hiller-Sturmhöfel, S

    2001-01-01

    The relationship between child abuse and the use or abuse of alcohol has two aspects. First, some findings have indicated that parental alcohol abuse may be associated with the physical or sexual abuse of children. Research findings in this area remain inconsistent, however. Second, the experience of being abused as a child may increase a person's risk for alcohol-related problems as an adult. This relationship has best been demonstrated in women who had been victims of childhood abuse. Several factors most likely contribute to or influence this relationship, including coping skills; antisocial behavior; and psychological problems, such as posttraumatic stress disorder.

  13. Effects of ethanol on immune response in the brain: region-specific changes in aged mice.

    PubMed

    Kane, Cynthia J M; Phelan, Kevin D; Douglas, James C; Wagoner, Gail; Johnson, Jennifer Walker; Xu, Jihong; Drew, Paul D

    2013-05-23

    Alcohol abuse has dramatic effects on the health of the elderly. Recent studies indicate that ethanol increases immune activity in younger animals and that some of these proinflammatory molecules alter alcohol consumption and addiction. However, the effects of alcohol on immune activation in aged animals have not been thoroughly investigated. We compared the effects of ethanol on chemokine and cytokine expression in the hippocampus, cerebellum, and cerebral cortex of aged C57BL/6 mice. Mice were treated via gavage with 6 g/kg ethanol for 10 days and tissue was harvested 1 day post-treatment. Ethanol selectively increased mRNA levels of the chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 in the hippocampus and cerebellum, but not in the cortex of aged mice relative to control animals. In this paradigm, ethanol did not affect mRNA levels of the cytokines IL-6 or TNF-α in any of these brain regions in aged animals. Collectively, these data indicate a region-specific susceptibility to ethanol regulation of neuroinflammatory and addiction-related molecules in aged mice. These studies could have important implications concerning alcohol-induced neuropathology and alcohol addiction in the elderly.

  14. Discrimination of ethanol-nicotine drug mixtures in mice: dual interactive mechanisms of overshadowing and potentiation

    PubMed Central

    Ford, Matthew M.; McCracken, Aubrey D.; Davis, Natalie L.; Ryabinin, Andrey E.; Grant, Kathleen A.

    2012-01-01

    Rationale One possible basis for the proclivity of ethanol and nicotine co-abuse is an interaction between the discriminative stimulus (SD) effects of each drug. Objectives The current work sought to assess the discriminative control of ethanol and nicotine cues in mice trained with drug mixtures and to determine whether interactive mechanisms of overshadowing and potentiation occur. Methods Male C57BL/6J mice were trained to discriminate ethanol (1.5 g/kg) alone or ethanol plus nicotine (0.4, 0.8 or 1.2 mg/kg base) in experiment 1, and nicotine (0.8 mg/kg) alone or nicotine plus ethanol (0.5, 1.0 or 2.0 g/kg) in experiment 2. Stimulus generalization of the training mixtures to ethanol, nicotine and the drug combination were assessed. Results Ethanol (1.5 g/kg) retained discriminative control despite the inclusion of a progressively larger nicotine dose within the training mixtures in experiment 1. Although the nicotine SD was overshadowed by ethanol training doses > 0.5 g/kg in experiment 2, nicotine did potentiate the effects of low dose ethanol. Conclusions These findings are suggestive of dual mechanisms whereby ethanol (>0.5 g/kg) overshadows the SD effects of nicotine, and at lower doses (< 1 g/kg) the salience of ethanol’s SD effects is potentiated by nicotine. These mechanisms may contribute to the escalation of concurrent drinking and smoking in a binge-like fashion. PMID:22763667

  15. Ethanol-induced dopamine elevation in the rat--modulatory effects by subchronic treatment with nicotinic drugs.

    PubMed

    Löf, Elin; Chau, Pei Pei; Stomberg, Rosita; Söderpalm, Bo

    2007-01-26

    Chronic nicotine administration is associated with increased ethanol consumption in laboratory animals and in humans. Some smokers report less sedation during acute ethanol intoxication after nicotine administration and the sedative effects from ethanol are mediated by inhibitory GABA(A)-receptors. In a series of in vivo microdialysis experiments we investigated whether subchronic pre-treatment with nicotinic drugs known to enhance ethanol consumption in the rat (nicotine or the peripheral nicotinic antagonist hexamethonium) could modulate the alterations in extracellular dopamine observed in response to administration of ethanol or the sedative GABA(A)-agonist diazepam. In the nucleus accumbens and the dorsal striatum, systemic and/or local ethanol administration resulted in transient increases in extracellular dopamine levels that returned to baseline before the local levels of ethanol started to decline. In hexamethonium pre-treated rats, however, the nucleus accumbens dopamine levels were time-locked to the ethanol levels in the same area after systemic or local ethanol administration. Perfusion of diazepam into the nucleus accumbens produced a significant reduction in nucleus accumbens dopamine in controls. Prior subchronic treatment with nicotine or hexamethonium abolished this effect. The present results suggest that subchronic treatment with the nicotinic acetylcholine receptor antagonist hexamethonium reduces a GABA(A)-R mediated counteraction of the nucleus accumbens dopamine response to ethanol. Additionally, we demonstrate that modulation of nicotinic receptors may reduce the sensitivity of GABA(A) receptors to benzodiazepines. These phenomena may offer a novel explanation to why nicotine and alcohol are often co-abused.

  16. Withdrawal from repeated treatment with ethanol induces a protracted decrease in novelty-seeking behavior and enhancement of environmental habituation in mice.

    PubMed

    Fukushiro, Daniela F; Saito, Luis P; Mári-Kawamoto, Elisa; Aramini, Tatiana C F; Costa, Jacqueline M; Josino, Fabiana S; Uehara, Regina A; Frussa-Filho, Roberto

    2012-03-01

    Ethanol withdrawal syndrome is characterized by somatic and behavioral symptoms, including increased anxiety and anhedonia. In animal models, however, there are many studies on the anxiogenic effects occurring during the first 24h after ethanol withdrawal, while anhedonia has been overlooked. Recently, we have found that amphetamine withdrawal reduced novelty seeking and enhanced environmental habituation in mice, two motivation-related behaviors. We now investigate the effects of withdrawal from ethanol, a drug of abuse with a different pharmacological profile, on these two motivation-related behaviors. Swiss male mice (3months old) were treated with 1.8g/kg ethanol for 21 consecutive days in their home cages. Seven days after ethanol withdrawal, mice were tested in a free-choice novelty apparatus containing one familiar and one novel compartment. Novelty-seeking behavior was assessed by comparing time spent in the novel compartment versus the familiar compartment, whereas environmental habituation was concomitantly evaluated by the time-response curve of total locomotion (novel+familiar). Novelty seeking was decreased and environmental habituation was enhanced during ethanol withdrawal. These anhedonic responses were not associated with concurrent changes in the anxiety-like behavior of mice (as confirmed in the elevated plus-maze test). We propose that the concomitant evaluation of novelty-seeking behavior and environmental habituation can be useful to study the behavioral consequences not only of amphetamine withdrawal but also of ethanol withdrawal. Furthermore, the present data support recent clinical findings that suggest the occurrence of protracted anhedonia well beyond the limited period immediately following the abrupt cessation of ethanol intake. Copyright © 2012. Published by Elsevier Inc.

  17. Oleoylethanolamide prevents neuroimmune HMGB1/TLR4/NF-kB danger signaling in rat frontal cortex and depressive-like behavior induced by ethanol binge administration.

    PubMed

    Antón, María; Alén, Francisco; Gómez de Heras, Raquel; Serrano, Antonia; Pavón, Francisco Javier; Leza, Juan Carlos; García-Bueno, Borja; Rodríguez de Fonseca, Fernando; Orio, Laura

    2017-05-01

    Alcohol abuse is frequently characterized by a specific pattern of intake in binge drinking episodes, inducing neuroinflammation and brain damage. Here, we characterized the temporal profile of neuroinflammation in rats exposed to intragastric binge ethanol administrations (3 times/day × 4 days) and tested the anti-inflammatory/neuroprotective properties of the satiety factor oleoylethanolamide (OEA). Pre-treatment with OEA (5 mg/kg, i.p.) previous each alcohol gavage blocked the expression of high mobility group box 1 (HMGB1) danger signal and the innate immunity Toll-like receptors 4 (TLR4) in frontal cortex, and inhibited the nuclear factor-kappa B (NF-kB) proinflammatory cascade induced by alcohol binge administration. OEA reduced the levels of interleukin-1beta (IL-1β), the monocyte chemoattractant protein-1 (MCP-1), and the enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in ethanol binged animals. Elevations in plasma tumor necrosis factor alpha (TNF-α) and IL-1β after ethanol were also inhibited by OEA. OEA also prevented ethanol-induced lipid peroxidation, caspase-8 and pro-apoptotic caspase-3 activation in frontal cortex. Additionally, OEA blocked the rise in blood corticosterone levels after ethanol with no alteration in blood ethanol levels and may affect ethanol-induced gut permeability for endotoxin. Finally, OEA, administered as a pre-treatment during the ethanol binge, exerted antidepressant-like effects during acute withdrawal. Altogether, results highlight a beneficial profile of OEA as a potent anti-inflammatory, antioxidant, neuroprotective and antidepressant-like compound to treat alcohol abuse. © 2016 Society for the Study of Addiction.

  18. Chronic cocaine or ethanol exposure during adolescence alters novelty-related behaviors in adulthood.

    PubMed

    Stansfield, Kirstie H; Kirstein, Cheryl L

    2007-04-01

    Adolescence is a time of high-risk behavior and increased exploration. This developmental period is marked by a greater probability to initiate drug use and is associated with an increased risk to develop addiction and adulthood dependency and drug use at this time is associated with an increased risk. Human adolescents are predisposed toward an increased likelihood of risk-taking behaviors [Zuckerman M. Sensation seeking and the endogenous deficit theory of drug abuse. NIDA Res Monogr 1986;74:59-70.], including drug use or initiation. In the present study, adolescent animals were exposed to twenty days of either saline (0.9% sodium chloride), cocaine (20 mg/kg) or ethanol (1 g/kg) i.p. followed by a fifteen-day washout period. All animals were tested as adults on several behavioral measures including locomotor activity induced by a novel environment, time spent in the center of an open field, novelty preference and novel object exploration. Animals exposed to cocaine during adolescence and tested as adults exhibited a greater locomotor response in a novel environment, spent less time in the center of the novel open field and spent less time with a novel object, results that are indicative of a stress or anxiogenic response to novelty or a novel situation. Adolescent animals chronically administered ethanol and tested as adults, unlike cocaine-exposed were not different from controls in a novel environment, indicated by locomotor activity or time spent with a novel object. However, ethanol-exposed animals approached the novel object more, suggesting that exposure to ethanol during development may result in less-inhibited behaviors during adulthood. The differences in adult behavioral responses after drug exposure during adolescence are likely due to differences in the mechanisms of action of the drugs and subsequent reward and/or stress responsivity. Future studies are needed to determine the neural substrates of these long lasting drug-induced changes.

  19. Fetal Abuse.

    ERIC Educational Resources Information Center

    Kent, Lindsey; And Others

    1997-01-01

    Five cases of fetal abuse by mothers suffering from depression are discussed. Four of the women had unplanned pregnancies and had considered termination of the pregnancy. Other factors associated with fetal abuse include pregnancy denial, pregnancy ambivalence, previous postpartum depression, and difficulties in relationships. Vigilance for…

  20. [Evaluation of selected socioeconomic factors in patients with acute ethanol intoxication and alcohol withdrawal syndrome].

    PubMed

    Lukasik-Głębocka, Magdalena; Sommerfeld, Karina

    2014-01-01

    Ethanol is commonly overused psychoactive substance in Poland and all around the world. It causes addiction, which occurs as a result of its chronic administration. One of the main symptoms of addiction is hunger due to psychoactive substance that prevents interruption of its adoption and contributes to relapse drinking. Acute poisoning with ethyl alcohol and alcohol withdrawal syndrome are diseases causing a potential danger to life. The prevalence of use and abuse of alcoholic beverages is a potential risk, causing health problems, including permanent damage of the central and peripheral nervous system and socio-economic problems. The aim of this study is to analyze certain aspects of the socio-economic situation of the patients hospitalized in the Department of Toxicology in Raszeja City Hospital in Poznan due to acute ethanol intoxication or alcohol withdrawal syndrome in 2010. 299 patients history was evaluated, among which 161 were treated for acute intoxication with ethanol and 138 due to alcohol withdrawal syndrome. Objects of interest were elements of subjective tests including: marital status of patients, their education and professional activity and the problem of homelessness. The study group consisted of 299 patients in age from 16 to 77 years, hospitalized in the Department of Toxicology in Raszeja City Hospital in Poznan due to acute ethanol intoxication or alcohol withdrawal syndrome. It was found that the largest group consisted of patients remaining married (42.81%) and unmarried (30.43%). Alcohol abuse affects people of all levels of education. In the present study, most patients had a vocational education (37.79%) and medium (23.08%). Patients were analyzed in terms of economic activity, among which about 40% were unemployed. In the whole group more than 10% of those were homeless. Ethyl alcohol intoxication and alcohol withdrawal represents a significant hazard. As a result of reliance, patients lose control of alcohol consumption and they

  1. Cognitive and emotional differences between abusive and non-abusive fathers.

    PubMed

    Francis, Karen J; Wolfe, David A

    2008-12-01

    Abusive fathers perpetrate a substantial portion of child physical abuse. Despite this, little is known about how they differ from non-abusive fathers. This study compared a broad range of cognitive and affective factors between physically abusive and non-abusive fathers. Abusive (n=24) and non-abusive (n=25) fathers completed standard measures assessing their experience and expression of anger, mental health, parenting stress, and their empathy and perceptions of children's socio-emotional signals. Abusive fathers differed from comparisons on almost all constructs. They experienced more anger and were more likely to express that anger aggressively. They reported more mental health concerns (such as depression, hostility, and paranoid ideation), more stress in parenting, and significantly less empathy for their children. They were also more likely to perceive children's emotional expressions as depicting negative emotions, such as anger and disgust. Abusive fathers struggle with a myriad of difficulties that likely contribute to their problematic parenting. These difficulties are both inter- and intra-personal in nature. The findings suggest that abusive fathers require comprehensive assessment that includes mental health screening. Interventions should be selected carefully to target abusive fathers' high levels of negative affect and negative perceptions. Treatment strategies should address problems related to parenting style (e.g., managing stress and interpretation of children's socioemotional signals) as well as their personal adjustment (e.g., cognitive behavioral strategies for regulating affect and cognitive distortions).

  2. Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia

    PubMed Central

    Raju, Sammeta V.; Wang, Guoshun

    2012-01-01

    Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (ISC) in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A2B adenosine receptor (A2BAR), largely abolished the adenosine-stimulated chloride transport, suggesting that A2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections. PMID:22442662

  3. Environmental enrichment reduces chronic psychosocial stress-induced anxiety and ethanol-related behaviors in mice.

    PubMed

    Bahi, Amine

    2017-07-03

    Previous research from our laboratory has shown that exposure to chronic psychosocial stress increased voluntary ethanol consumption and preference as well as acquisition of ethanol-induced conditioned place preference (CPP) in mice. This study was done to determine whether an enriched environment could have "curative" effects on chronic psychosocial stress-induced ethanol intake and CPP. For this purpose, experimental mice "intruders" were exposed to the chronic subordinate colony (CSC) housing for 19 consecutive days in the presence of an aggressive "resident" mouse. At the end of that period, mice were tested for their anxiety-like behavior using the elevated plus maze (EPM) test then housed in a standard or enriched environment (SE or EE respectively). Anxiety and ethanol-related behaviors were investigated using the open field (OF) test, a standard two-bottle choice drinking paradigm, and the CPP procedure. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to single housed colony (SHC) controls. In addition, CSC exposure increased voluntary ethanol intake and ethanol-CPP. Interestingly, we found that EE significantly and consistently reduced anxiety and ethanol consumption and preference. However, neither tastants' (saccharin and quinine) intake nor blood ethanol metabolism were affected by EE. Finally, and most importantly, EE reduced the acquisition of CPP induced by 1.5g/kg ethanol. Taken together, these results support the hypothesis that EE can reduce voluntary ethanol intake and ethanol-induced conditioned reward and seems to be one of the strategies to reduce the behavioral deficits and the risk of anxiety-induced alcohol abuse. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Prescription Drug Abuse

    MedlinePlus

    ... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that ... purpose, such as getting high Abusing some prescription drugs can lead to addiction. These include opioids, sedatives, ...

  5. Ethanol and Protein from Ethanol Plant By-Products Using Edible Fungi Neurospora intermedia and Aspergillus oryzae.

    PubMed

    Bátori, Veronika; Ferreira, Jorge A; Taherzadeh, Mohammad J; Lennartsson, Patrik R

    2015-01-01

    Feasible biorefineries for production of second-generation ethanol are difficult to establish due to the process complexity. An alternative is to partially include the process in the first-generation plants. Whole stillage, a by-product from dry-mill ethanol processes from grains, is mostly composed of undegraded bran and lignocelluloses can be used as a potential substrate for production of ethanol and feed proteins. Ethanol production and the proteins from the stillage were investigated using the edible fungi Neurospora intermedia and Aspergillus oryzae, respectively. N. intermedia produced 4.7 g/L ethanol from the stillage and increased to 8.7 g/L by adding 1 FPU of cellulase/g suspended solids. Saccharomyces cerevisiae produced 0.4 and 5.1 g/L ethanol, respectively. Under a two-stage cultivation with both fungi, up to 7.6 g/L of ethanol and 5.8 g/L of biomass containing 42% (w/w) crude protein were obtained. Both fungi degraded complex substrates including arabinan, glucan, mannan, and xylan where reductions of 91, 73, 38, and 89% (w/v) were achieved, respectively. The inclusion of the current process can lead to the production of 44,000 m(3) of ethanol (22% improvement), around 12,000 tons of protein-rich biomass for animal feed, and energy savings considering a typical facility producing 200,000 m(3) ethanol/year.

  6. 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.

  7. Moderate ethanol preconditioning of rat brain cultures engenders neuroprotection against dementia-inducing neuroinflammatory proteins: possible signaling mechanisms.

    PubMed

    Collins, Michael A; Neafsey, Edward J; Wang, Kewei; Achille, Nicholas J; Mitchell, Robert M; Sivaswamy, Sreevidya

    2010-06-01

    There is no question that chronic alcohol (ethanol) abuse, a leading worldwide problem, causes neuronal dysfunction and brain damage. However, various epidemiologic studies in recent years have indicated that in comparisons with abstainers or never-drinkers, light/moderate alcohol consumers have lower risks of age-dependent cognitive decline and/or dementia, including Alzheimer's disease (AD). Such reduced risks have been variously attributed to favorable circulatory and/or cerebrovascular effects of moderate ethanol intake, but they could also involve ethanol "preconditioning" phenomena in brain glia and neurons. Here we summarize our experimental studies showing that moderate ethanol preconditioning (MEP; 20-30 mM ethanol) of rat brain cultures prevents neurodegeneration due to beta-amyloid, an important protein implicated in AD, and to other neuroinflammatory proteins such as gp120, the human immunodeficiency virus 1 envelope protein linked to AIDS dementia. The MEP neuroprotection is associated with suppression of neurotoxic protein-evoked initial increases in [Ca(+2)](i) and proinflammatory mediators--e.g., superoxide anion, arachidonic acid, and glutamate. Applying a sensor --> transducer --> effector model to MEP, we find that onset of neuroprotection correlates temporally with elevations in "effector" heat shock proteins (HSP70, HSP27, and phospho-HSP27). The effector status of HSPs is supported by the fact that inhibiting HSP elevations due to MEP largely restores gp120-induced superoxide potentiation and subsequent neurotoxicity. As upstream mediators, synaptic N-methyl-d-aspartate receptors may be initial prosurvival sensors of ethanol, and protein kinase C epsilon and focal adhesion kinase are likely transducers during MEP that are essential for protective HSP elevations. Regarding human consumption, we speculate that moderate ethanol intake might counter incipient cognitive deterioration during advanced aging or AD by exerting preconditioning

  8. Glycine Receptors Containing α2 or α3 Subunits Regulate Specific Ethanol-Mediated Behaviors

    PubMed Central

    Blednov, Yuri A.; Benavidez, Jillian M.; Black, Mendy; Leiter, Courtney R.; Osterndorff-Kahanek, Elizabeth

    2015-01-01

    Glycine receptors (GlyRs) are broadly expressed in the central nervous system. Ethanol enhances the function of brain GlyRs, and the GlyRα1 subunit is associated with some of the behavioral actions of ethanol, such as loss of righting reflex. The in vivo role of GlyRα2 and α3 subunits in alcohol responses has not been characterized despite high expression levels in the nucleus accumbens and amygdala, areas that are important for the rewarding properties of drugs of abuse. We used an extensive panel of behavioral tests to examine ethanol actions in mice lacking Glra2 (the gene encoding the glycine receptor alpha 2 subunit) or Glra3 (the gene encoding the glycine receptor alpha 3 subunit). Deletion of Glra2 or Glra3 alters specific ethanol-induced behaviors. Glra2 knockout mice demonstrate reduced ethanol intake and preference in the 24-hour two-bottle choice test and increased initial aversive responses to ethanol and lithium chloride. In contrast, Glra3 knockout mice show increased ethanol intake and preference in the 24-hour intermittent access test and increased development of conditioned taste aversion to ethanol. Mutants and wild-type mice consumed similar amounts of ethanol in the limited access drinking in the dark test. Other ethanol effects, such as anxiolysis, motor incoordination, loss of righting reflex, and acoustic startle response, were not altered in the mutants. The behavioral changes in mice lacking GlyRα2 or α3 subunits were distinct from effects previously observed in mice with knock-in mutations in the α1 subunit. We provide evidence that GlyRα2 and α3 subunits may regulate ethanol consumption and the aversive response to ethanol. PMID:25678534

  9. The combination of ethanol with mephedrone increases the signs of neurotoxicity and impairs neurogenesis and learning in adolescent CD-1 mice

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

    Ciudad-Roberts, Andrés; Duart-Castells, Leticia; Camarasa, Jorge

    A new family of psychostimulants, under the name of cathinones, has broken into the market in the last decade. In light of the fact that around 95% of cathinone consumers have been reported to combine them with alcoholic drinks, we sought to study the consequences of the concomitant administration of ethanol on mephedrone -induced neurotoxicity. Adolescent male Swiss-CD1 mice were administered four times in one day, every 2 h, with saline, mephedrone (25 mg/kg), ethanol (2; 1.5; 1.5; 1 g/kg) and their combination at a room temperature of 26 ± 2 °C. The combination with ethanol impaired mephedrone-induced decreases inmore » dopamine transporter and tyrosine hydroxylase in the frontal cortex; and in serotonin transporter and tryptophan hydroxylase in the hippocampus by approximately 2-fold, 7 days post-treatment. Furthermore, these decreases correlated with a 2-fold increase in lipid peroxidation, measured as concentration of malondialdehyde (MDA), 24 h post-treatment, and were accompanied by changes in oxidative stress-related enzymes. Ethanol also notably potentiated mephedrone-induced negative effects on learning and memory, as well as hippocampal neurogenesis, measured through the Morris water maze (MWM) and 5-bromo-2′-deoxyuridine staining, respectively. These results are of special significance, since alcohol is widely co-abused with amphetamine derivatives such as mephedrone, especially during adolescence, a crucial stage in brain maturation. Given that the hippocampus is greatly involved in learning and memory processes, normal brain development in young adults could be affected with permanent behavioral consequences after this type of drug co-abuse. - Highlights: • Mice were administered a binge regimen of mephedrone plus/minus ethanol. • Ethanol exacerbated mephedrone-induced changes in 5-HT and DA function markers. • Neurochemical alterations were accompanied by an increase in oxidative stress. • Ethanol potentiated mephedrone

  10. Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice

    PubMed Central

    Deshpande, Krutika T.; Liu, Shinlan; McCracken, Jennifer M.; Jiang, Lu; Gaw, Ta Ehpaw; Kaydo, Lindsey N.; Richard, Zachary C.; O’Neil, Maura F.; Pritchard, Michele T.

    2016-01-01

    Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl4-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl4 exposure. Mice were fed moderate ethanol (2% v/v) for two days and then were exposed to CCl4 and euthanized 24–96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl4-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl4 exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl4-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl4. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure. PMID:26751492

  11. The effects of ghrelin antagonists [D-Lys(3) ]-GHRP-6 or JMV2959 on ethanol, water, and food intake in C57BL/6J mice.

    PubMed

    Gomez, Juan L; Ryabinin, Andrey E

    2014-09-01

    Alcohol use and abuse patterns have created a need for novel treatment models. Current research has turned its focus on reward pathways associated with intrinsic necessities, such as feeding. Theories suggest that drugs of abuse seize control of natural reward pathways and dysregulate normal function, leading to chronic addiction. One such pathway involving the hunger stimulating peptide, ghrelin, is the focus of our study. Male C57BL/6J mice were randomly assigned to groups and treated with vehicle or a ghrelin antagonist, either [D-Lys(3) ]-GHRP-6 (DLys) or JMV2959. Three experiments tested ghrelin antagonism using different doses; experiment 1 tested 12 mg/kg JMV2959; experiment 2 tested 15 mg/kg DLys; experiment 3 tested 9 mg/kg JMV2959. Using a 2-bottle choice 24-hour access paradigm, data were collected for ethanol intake, preference, water intake, and food intake at 4 and 24 hours after injection. Experiment 1 showed that 12 mg/kg of JMV2959 decreased ethanol, water, and food intake, without affecting preference. Experiment 2 showed that 15 mg/kg of DLys decreased ethanol intake, preference, and water intake only on the first day of treatment. Experiment 3 showed that 9 mg/kg of JMV2959 decreased only ethanol and food intake. No change was seen during deprivation, and JMV2959 was still effective at reducing ethanol intake upon reintroduction. Despite the change in food intake, there were no differences in body weight throughout the experiments. It should be noted that the majority of significant effects were only found 4 hours postinjection. The results show that compounds that block ghrelin receptor activity are effective at decreasing ethanol intake. However, DLys was only effective at reducing intake and preference on the first day, suggesting a quick tolerance and selectivity for ethanol. JMV2959 consistently reduced ethanol intake, but at the higher dose also reduced all other consummatory behaviors. Thus, ghrelin antagonists provide a viable potential

  12. Therapy of Pancreatic Neuroendocrine Tumors: Fine Needle Intervention including Ethanol and Radiofrequency Ablation

    PubMed Central

    Lakhtakia, Sundeep

    2017-01-01

    Pancreatic neuroendocrine tumors (PNETs) are increasingly being detected, though usually as incidental findings. Majority of the PNETs are non-functional and surgical resection is the standard of care for most of them. However, in patients with small PNETs localized within the pancreas, who are unfit or unwilling for surgery, alternate methods of treatment are needed. Direct methods of ablation of PNETs, using either ethanol injection or radiofrequency ablation (RFA), are emerging as effective methods. The limited literature available as case reports or case series on endoscopic ultrasound (EUS)-guided local ablation using either ethanol or RFA has demonstrated safety and efficacy along with short- to medium-term sustained relief. Long-term benefits with these local ablative therapies are awaited. Comparative studies are needed to show which of these two competing technologies is superior. Finally, comparative trials of EUS-guided ablation with surgical resection in terms of efficacy and safety will ensure their place in the management algorithm. PMID:29207860

  13. Corticotropin-Releasing Factor Critical for Zebrafish Camouflage Behavior Is Regulated by Light and Sensitive to Ethanol

    PubMed Central

    Wagle, Mahendra; Mathur, Priya; Guo, Su

    2011-01-01

    The zebrafish camouflage response is an innate “hard-wired” behavior that offers an excellent opportunity to explore neural circuit assembly and function. Moreover, the camouflage response is sensitive to ethanol, making it a tractable system for understanding how ethanol influences neural circuit development and function. Here we report the identification of corticotropin releasing factor (CRF) as a critical component of the camouflage response pathway. We further show that ethanol, having no direct effect on the visual sensory system or the melanocytes, acts downstream of retinal ganglion cells and requires the CRF-proopiomelanocortin (POMC) pathway to exert its effect on camouflage. Treatment with ethanol, as well as alteration of light exposure that changes sensory input into the camouflage circuit, robustly modifies CRF expression in subsets of neurons. Activity of both Adenylyl Cyclase 5 and Extracellular signal Regulated Kinase (ERK) is required for such ethanol- or light- induced plasticity of crf expression. These results reveal an essential role of a peptidergic pathway in camouflage that is regulated by light and influenced by ethanol at concentrations relevant to abuse and anxiolysis, in a cAMP- and ERK- dependent manner. We conclude that this ethanol-modulated camouflage response represents a novel and relevant system for molecular genetic dissection of a neural circuit that is regulated by light and sensitive to ethanol. PMID:21209207

  14. Corticotropin-releasing factor critical for zebrafish camouflage behavior is regulated by light and sensitive to ethanol.

    PubMed

    Wagle, Mahendra; Mathur, Priya; Guo, Su

    2011-01-05

    The zebrafish camouflage response is an innate "hard-wired" behavior that offers an excellent opportunity to explore neural circuit assembly and function. Moreover, the camouflage response is sensitive to ethanol, making it a tractable system for understanding how ethanol influences neural circuit development and function. Here we report the identification of corticotropin-releasing factor (CRF) as a critical component of the camouflage response pathway. We further show that ethanol, having no direct effect on the visual sensory system or the melanocytes, acts downstream of retinal ganglion cells and requires the CRF-proopiomelanocortin pathway to exert its effect on camouflage. Treatment with ethanol, as well as alteration of light exposure that changes sensory input into the camouflage circuit, robustly modifies CRF expression in subsets of neurons. Activity of both adenylyl cyclase 5 and extracellular signal-regulated kinase (ERK) is required for such ethanol-induced or light-induced plasticity of crf expression. These results reveal an essential role of a peptidergic pathway in camouflage that is regulated by light and influenced by ethanol at concentrations relevant to abuse and anxiolysis, in a cAMP-dependent and ERK-dependent manner. We conclude that this ethanol-modulated camouflage response represents a novel and relevant system for molecular genetic dissection of a neural circuit that is regulated by light and sensitive to ethanol.

  15. Establishing "abuse-deterrence equivalence" for generic abuse-deterrent opioid formulations: A proposed development framework.

    PubMed

    Setnik, Beatrice; Cone, Edward J

    2016-01-01

    Abuse-deterrent formulations are one strategy for mitigating the epidemic of prescription opioid abuse. Regulatory guidance documents describe the requirements for developing abuse-deterrent formulations of novel drugs and formulations; however, they do not address "abuse-deterrence equivalence" for generic formulations. As generics may be produced with different excipients and formulations compared to reference drugs, differences in their properties may impact their abuse-deterrent features. Currently, it is unclear what specific studies are needed to support generic abuse-deterrence claims. This commentary outlines several recommendations on the in vitro and in vivo testing required, including the conditions for conducting a human abuse potential study.

  16. Ethanol and Protein from Ethanol Plant By-Products Using Edible Fungi Neurospora intermedia and Aspergillus oryzae

    PubMed Central

    Bátori, Veronika; Ferreira, Jorge A.; Taherzadeh, Mohammad J.; Lennartsson, Patrik R.

    2015-01-01

    Feasible biorefineries for production of second-generation ethanol are difficult to establish due to the process complexity. An alternative is to partially include the process in the first-generation plants. Whole stillage, a by-product from dry-mill ethanol processes from grains, is mostly composed of undegraded bran and lignocelluloses can be used as a potential substrate for production of ethanol and feed proteins. Ethanol production and the proteins from the stillage were investigated using the edible fungi Neurospora intermedia and Aspergillus oryzae, respectively. N. intermedia produced 4.7 g/L ethanol from the stillage and increased to 8.7 g/L by adding 1 FPU of cellulase/g suspended solids. Saccharomyces cerevisiae produced 0.4 and 5.1 g/L ethanol, respectively. Under a two-stage cultivation with both fungi, up to 7.6 g/L of ethanol and 5.8 g/L of biomass containing 42% (w/w) crude protein were obtained. Both fungi degraded complex substrates including arabinan, glucan, mannan, and xylan where reductions of 91, 73, 38, and 89% (w/v) were achieved, respectively. The inclusion of the current process can lead to the production of 44,000 m3 of ethanol (22% improvement), around 12,000 tons of protein-rich biomass for animal feed, and energy savings considering a typical facility producing 200,000 m3 ethanol/year. PMID:26682213

  17. Transgenic Over Expression of Nicotinic Receptor Alpha 5, Alpha 3, and Beta 4 Subunit Genes Reduces Ethanol Intake in Mice

    PubMed Central

    Gallego, Xavier; Ruiz, Jessica; Valverde, Olga; Molas, Susanna; Robles, Noemí; Sabrià, Josefa; Crabbe, John C.; Dierssen, Mara

    2012-01-01

    Abuse of alcohol and smoking are extensively co-morbid. Some studies suggest partial commonality of action of alcohol and nicotine mediated through nicotinic acetylcholine receptors (nAChRs). We tested mice with transgenic over expression of the alpha 5, alpha 3, beta 4 receptor subunit genes, which lie in a cluster on human chromosome 15, that were previously shown to have increased nicotine self-administration, for several responses to ethanol. Transgenic and wild-type mice did not differ in sensitivity to several acute behavioral responses to ethanol. However, transgenic mice drank less ethanol than wild-type in a two-bottle (ethanol vs. water) preference test. These results suggest a complex role for this receptor subunit gene cluster in the modulation of ethanol’s as well as nicotine’s effects. PMID:22459873

  18. Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings

    PubMed Central

    Bell, Richard L.; Hauser, Sheketha R.; McClintick, Jeanette; Rahman, Shafiqur; Edenberg, Howard J.; Szumlinski, Karen K.; McBride, William J.

    2016-01-01

    Herein, we have reviewed the role of glutamate, the major excitatory neurotransmitter in the brain, in a number of neurochemical, -physiological, and -behavioral processes mediating the development of alcohol dependence. The findings discussed include results from both preclinical as well as neuroimaging and postmortem clinical studies. Expression levels for a number of glutamate-associated genes and/or proteins are modulated by alcohol abuse and dependence. These changes in expression include metabotropic receptors and ionotropic receptor subunits as well as different glutamate transporters. Moreover, these changes in gene expression parallel the pharmacologic manipulation of these same receptors and transporters. Some of these gene expression changes may have predated alcohol abuse and dependence because a number of glutamate-associated polymorphisms are related to a genetic predisposition to develop alcohol dependence. Other glutamate-associated polymorphisms are linked to age at the onset of alcohol-dependence and initial level of response/sensitivity to alcohol. Finally, findings of innate and/or ethanol-induced glutamate-associated gene expression differences/changes observed in a genetic animal model of alcoholism, the P rat, are summarized. Overall, the existing literature indicates that changes in glutamate receptors, transporters, enzymes, and scaffolding proteins are crucial for the development of alcohol dependence and there is a substantial genetic component to these effects. This indicates that continued research into the genetic underpinnings of these glutamate-associated effects will provide important novel molecular targets for treating alcohol abuse and dependence. PMID:26809998

  19. Sexual abuse in children - what to know

    MedlinePlus

    Sexual abuse - children ... abused before they turn 18. Sexual abuse of children is any activity that the abuser does to get sexually aroused, including: Touching a child's genitals Rubbing the abuser's genitals against a child's ...

  20. A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule

    PubMed Central

    Amato, Russell J.; Hulin, Mary W.; Winsauer, Peter J.

    2012-01-01

    Dehydroepiandrosterone (DHEA), 7-keto DHEA, and several comparison drugs (ethanol, chlordiazepoxide, rauwolscine, and RO15-4513) were administered to male rats responding under a multiple schedule of food and ethanol presentation to determine their selectively for decreasing ethanol-maintained responding. DHEA and 7-keto DHEA significantly decreased both ethanol- and food-maintained responding, compared to control, while also decreasing blood ethanol concentration (BEC). Acute ethanol administration also decreased responding for both food and ethanol; however, ethanol-maintained responding was more potently decreased than food-maintained responding. BEC remained relatively stable after increasing ethanol doses. Among the other drugs tested, RO15-4513 was the most selective for decreasing ethanol-maintained responding compared to food-maintained responding, and it decreased BECs as ethanol-maintained responding decreased. The largest dose of rauwolscine significantly decreased responding for food, while not affecting ethanol-maintained responding compared to control. Low to intermediate doses of rauwolscine produced small, non-significant increases in ethanol-maintained responding and BECs. Chlordiazepoxide produced significant decreases in food-maintained responding and the dose of ethanol presented, but only at the highest dose tested. Although DHEA and 7-keto DHEA did not decrease ethanol-maintained responding as selectively as ethanol or RO15-4513 under the multiple schedule, these neurosteroids may be valuable pharmacological tools in the development of new treatments for alcohol abuse and dependence. PMID:22473025

  1. Development of Ethanol Withdrawal-Related Sensitization and Relapse Drinking in Mice Selected for High or Low Ethanol Preference

    PubMed Central

    Lopez, Marcelo F.; Grahame, Nicholas J.; Becker, Howard C.

    2010-01-01

    Background Previous studies have shown that high alcohol consumption is associated with low withdrawal susceptiblility, while at the same time, other studies have shown that exposure to ethanol vapor increases alcohol drinking in rats and mice. In the present studies, we sought to shed light on this seeming contradiction by using mice selectively bred for High- (HAP) and Low- (LAP) Alcohol Preference, first, assessing these lines for differences in signs of ethanol withdrawal and second, for differences in the efficacy of intermittent alcohol vapor exposure on elevating subsequent ethanol intake. Methods Experiment 1 examined whether these lines of mice differed in ethanol withdrawal-induced CNS hyperexcitability and the development of sensitization to this effect following intermittent ethanol vapor exposure. Adult HAP and LAP lines (replicates 1 and 2), and the C3H/HeNcr inbred strain (included as a control genotype for comparison purposes) received intermittent exposure to ethanol vapor and were evaluated for ethanol withdrawal-induced seizures assessed by scoring handling-induced convulsions (HIC). Experiment 2 examined the influence of chronic intermittent ethanol exposure on voluntary ethanol drinking. Adult male and female HAP-2 and LAP-2 mice, along with male C57BL/6J (included as comparative controls) were trained to drink 10% ethanol using a limited access (2 hr/day) 2-bottle choice paradigm. After stable baseline daily intake was established, mice received chronic intermittent ethanol vapor exposure in inhalation chambers. Ethanol intake sessions resumed 72 hr after final ethanol (or air) exposure for 5 consecutive days. Results Following chronic ethanol treatment, LAP mice exhibited overall greater withdrawal seizure activity compared to HAP mice. In Experiment 2, chronic ethanol exposure/withdrawal resulted in a significant increase in ethanol intake in male C57BL/6J, and modestly elevated intake in HAP-2 male mice. Ethanol intake for male control mice

  2. [Proposal for early detection of ethanol consumption in students of the Universidad Autónoma del Estado de Morelos].

    PubMed

    García-Jiménez, Sara; Erazo-Mijares, Miguel; Toledano-Jaimes, Cairo D; Monroy-Noyola, Antonio; Bilbao-Marcos, Fernando; Sánchez-Alemán, Miguel A; Déciga-Campos, Myrna

    2016-01-01

    The present study determined through analytic techniques the quantification of some biomarkers that have been useful to detect early ethanol consumption in a college population. A group of 117 students of recent entry to the Universidad Autónoma del Estado de Morelos was analyzed. The enzyme determination of aspartate aminotransferase, alanine aminotransferase, and gamma glutamyltransferase as metabolic markers of ethanol, as well as the carbohydrate-deficient transferrin (CDT) detected by high chromatographic liquid (up to 1.8% of CDT), allowed us to identify that 6% of the college population presented a potential risk of alcohol consumption. The use of the biochemical-analytical method overall with the psychological drug and a risk factor instrument established by the Universidad Autónoma del Estado de Morelos permit us to identify students whose substance abuse consumption puts their terminal efficiency at risk as well as their academic level. The timely detection on admission to college can monitor and support a student consumer's substance abuse.

  3. Ethanol-induced conditioned taste avoidance: reward or aversion?

    PubMed

    Liu, Chuang; Showalter, John; Grigson, Patricia Sue

    2009-03-01

    Rats avoid intake of a palatable taste cue when paired with all drugs of abuse tested. Evidence suggests that, at least for morphine and cocaine, rats avoid the taste cue because they are anticipating the rewarding properties of the drug. Thus, the suppressive effects of a rewarding sucrose solution and cocaine, but not those of the putatively aversive agent, lithium chloride (LiCl), are exaggerated in drug-sensitive Lewis rats. Likewise, the suppressive effects of sucrose and morphine, but not those of LiCl, are eliminated by bilateral lesions of the gustatory thalamus. Unlike morphine and cocaine, it is less clear whether rewarding or aversive drug properties are responsible for ethanol-induced suppression of intake of a taste cue. The present set of studies tests whether, like cocaine, ethanol-induced suppression of intake of a taste cue also is greater in the drug-sensitive Lewis rats and whether the suppressive effects of the drug are prevented by bilateral lesions of the taste thalamus. In Experiment 1, fluid-deprived Lewis and Fischer rats were given 5-minute access to 0.15% saccharin and then injected with saline or a range of doses of ethanol (0.5, 0.75, 1.0, or 1.5 g/kg). There was a total of 6 such pairings. In Experiments 2 and 3, Sprague-Dawley rats received bilateral electrophysiologically guided lesions of the gustatory thalamus. After recovery, suppression of intake of the saccharin cue was evaluated following repeated daily pairings with either a high (1.5 g/kg) or a low (0.75 g/kg) dose of ethanol. Ethanol-induced suppression of intake of the saccharin conditioned stimulus (CS) did not differ between the drug-sensitive Lewis rats relative to the less-sensitive Fischer rats. Lesions of the taste thalamus, however, prevented the suppressive effect of the 0.75 g/kg dose of the drug, but had no impact on the suppressive effect of the 1.5 g/kg dose of ethanol. The results suggest that the suppressive effects of ethanol on CS intake are mediated by both

  4. The complexities of elder abuse.

    PubMed

    Roberto, Karen A

    2016-01-01

    Elder abuse is a growing societal concern, affecting at least 1 in 10 older Americans. Researchers and practitioners alike consistently assert that a dramatic discrepancy exists between the prevalence rates of elder abuse and the number of elder abuse cases reported. As a field of study, recognition and understanding of elder abuse is still emerging. Comparing findings of a small, but growing, body of literature on perceived and substantiated cases of elder abuse is challenging because there is no uniform term or agreed-upon definition used among state governments, researchers, health care and service providers, and advocates. This article summarizes current understanding of elder abuse, including what constitutes elder abuse, risk factors for elder abuse, perpetrators of elder abuse, and outcomes of elder abuse. Issues associated with the detection of elder abuse and intervention strategies for victims of abuse are addressed. In the final section, potential roles and contributions of psychologists for advancing elder abuse research, professional practice, and policy development are highlighted. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  5. Dextromethorphan Abuse in Adolescence

    PubMed Central

    Bryner, Jodi K.; Wang, Uerica K.; Hui, Jenny W.; Bedodo, Merilin; MacDougall, Conan; Anderson, Ilene B.

    2008-01-01

    Objectives To analyze the trend of dextromethorphan abuse in California and to compare these findings with national trends. Design A 6-year retrospective review. Setting California Poison Control System (CPCS), American Association of Poison Control Centers (AAPCC), and Drug Abuse Warning Network (DAWN) databases from January 1, 1999, to December 31, 2004. Participants All dextromethorphan abuse cases reported to the CPCS, AAPCC, and DAWN. The main exposures of dextromethorphan abuse cases included date of exposure, age, acute vs long-term use, coingestants, product formulation, and clinical outcome. Main Outcome Measure The annual proportion of dextromethorphan abuse cases among all exposures reported to the CPCS, AAPCC, and DAWN databases. Results A total of 1382 CPCS cases were included in the study. A 10-fold increase in CPCS dextromethorphan abuse cases from 1999 (0.23 cases per 1000 calls) to 2004 (2.15 cases per 1000 calls) (odds ratio, 1.48; 95% confidence interval, 1.43–1.54) was identified. Of all CPCS dextromethorphan abuse cases, 74.5% were aged 9 to 17 years; the frequency of cases among this age group increased more than 15-fold during the study (from 0.11 to 1.68 cases per 1000 calls). Similar trends were seen in the AAPCC and DAWN databases. The highest frequency of dextromethorphan abuse occurred among adolescents aged 15 and 16 years. The most commonly abused product was Coricidin HBP Cough & Cold Tablets. Conclusions Our study revealed an increasing trend of dextromethorphan abuse cases reported to the CPCS that is paralleled nationally as reported to the AAPCC and DAWN. This increase was most evident in the adolescent population. PMID:17146018

  6. Endogenous Opioids as Substrates for Ethanol Intake in the Neonatal Rat: The impact of prenatal ethanol exposure on the opioid family in the early postnatal period

    PubMed Central

    Bordner, Kelly; Deak, Terrence

    2015-01-01

    Background Despite considerable knowledge that prenatal ethanol exposure can lead to devastating effects on the developing fetus, alcohol consumption by pregnant women remains strikingly prevalent. Both clinical and basic research has suggested that, in addition to possible physical, behavioral, and cognitive deficits, gestational exposure to alcohol may lead to an increased risk for the development of later alcohol-related use and abuse disorders. The current work sought to characterize alterations in endogenous opioid signaling peptides and gene expression produced by ethanol exposure during the last days of gestation. Methods Experimental subjects were 4-, 8-, and 12-day old infant rats obtained from pregnant females that were given daily intubations of 0, 1, or 2 g/kg ethanol during the last few days of gestation (GD17-20). Using real-time RT-PCR, western blotting analysis, and enzyme immunoassays, we examined mRNA and protein for three opioid receptors and ligands in the nucleus accumbens, ventral tegmental area, and hypothalamus. Results Three main trends emerged - (1) mRNA for the majority of factors were found to upregulate across each of the three postnatal ages assessed, indicative of escalating ontogenetic expression of opioid-related genes; (2) prenatal ethanol significantly reduced many opioid peptides, suggesting a possible mechanism by which prenatal exposure can affect future responsiveness towards ethanol; and (3) the nucleus accumbens emerged as a key site for ethanol-dependent effects, suggesting a potential target for additional assessment and intervention towards understanding the ethanol's ability to program the developing brain. Conclusion We provide a global assessment of relatively long-term changes in both opioid gene expression and protein following exposure to only moderate amounts of ethanol during a relatively short window in the prenatal period. These results suggest that, while continuing to undergo ontogenetic changes, the infant

  7. Endogenous opioids as substrates for ethanol intake in the neonatal rat: The impact of prenatal ethanol exposure on the opioid family in the early postnatal period.

    PubMed

    Bordner, Kelly; Deak, Terrence

    2015-09-01

    Despite considerable knowledge that prenatal ethanol exposure can lead to devastating effects on the developing fetus, alcohol consumption by pregnant women remains strikingly prevalent. Both clinical and basic research has suggested that, in addition to possible physical, behavioral, and cognitive deficits, gestational exposure to alcohol may lead to an increased risk for the development of later alcohol-related use and abuse disorders. The current work sought to characterize alterations in endogenous opioid signaling peptides and gene expression produced by ethanol exposure during the last days of gestation. Experimental subjects were 4-, 8-, and 12-day old infant rats obtained from pregnant females that were given daily intubations of 0, 1, or 2g/kg ethanol during the last few days of gestation (GDs 17-20). Using real-time RT-PCR, western blotting analysis, and enzyme immunoassays, we examined mRNA and protein for three opioid receptors and ligands in the nucleus accumbens, ventral tegmental area, and hypothalamus. Three main trends emerged - (1) mRNA for the majority of factors was found to upregulate across each of the three postnatal ages assessed, indicative of escalating ontogenetic expression of opioid-related genes; (2) prenatal ethanol significantly reduced many opioid peptides, suggesting a possible mechanism by which prenatal exposure can affect future responsiveness towards ethanol; and (3) the nucleus accumbens emerged as a key site for ethanol-dependent effects, suggesting a potential target for additional assessment and intervention towards understanding the ethanol's ability to program the developing brain. We provide a global assessment of relatively long-term changes in both opioid gene expression and protein following exposure to only moderate amounts of ethanol during a relatively short window in the prenatal period. These results suggest that, while continuing to undergo ontogenetic changes, the infant brain is sensitive to prenatal ethanol

  8. The Unique Dopamine/Ecdysteroid Receptor Modulates Ethanol-Induced Sedation in Drosophila

    PubMed Central

    Petruccelli, Emily; Li, Qi; Rao, Yi

    2016-01-01

    Steroids profoundly influence behavioral responses to alcohol by activating canonical nuclear hormone receptors and exerting allosteric effects on ion channels. Accumulating evidence has demonstrated that steroids can also trigger biological effects by directly binding G-protein-coupled receptors (GPCRs), yet physiological roles of such unconventional steroid signaling in controlling alcohol-induced behaviors remain unclear. The dopamine/ecdysteroid receptor (DopEcR) is a GPCR that mediates nongenomic actions of ecdysteroids, the major steroid hormones in insects. Here, we report that Drosophila DopEcR plays a critical role in ethanol-induced sedation. DopEcR mutants took longer than control flies to become sedated during exposure to ethanol, despite having normal ethanol absorption or metabolism. RNAi-mediated knockdown of DopEcR expression revealed that this receptor is necessary after eclosion, and is required in particular neuronal subsets, including cholinergic and peptidergic neurons, to mediate this behavior. Additionally, flies ubiquitously overexpressing DopEcR cDNA had a tendency to become sedated quickly upon ethanol exposure. These results indicate that neuronal subset-specific expression of DopEcR in adults is required for normal sedation upon exposure to ethanol. We also obtained evidence indicating that DopEcR may promote ethanol sedation by suppressing epidermal growth factor receptor/extracellular signal-regulated kinase signaling. Last, genetic and pharmacological analyses suggested that in adult flies ecdysone may serve as an inverse agonist of DopEcR and suppress the sedation-promoting activity of DopEcR in the context of ethanol exposure. Our findings provide the first evidence for the involvement of nongenomic G-protein-coupled steroid receptors in the response to alcohol, and shed new light on the potential roles of steroids in alcohol-use disorders. SIGNIFICANCE STATEMENT Alcohol abuse is an alarming personal and societal burden. The

  9. The Unique Dopamine/Ecdysteroid Receptor Modulates Ethanol-Induced Sedation in Drosophila.

    PubMed

    Petruccelli, Emily; Li, Qi; Rao, Yi; Kitamoto, Toshihiro

    2016-04-20

    Steroids profoundly influence behavioral responses to alcohol by activating canonical nuclear hormone receptors and exerting allosteric effects on ion channels. Accumulating evidence has demonstrated that steroids can also trigger biological effects by directly binding G-protein-coupled receptors (GPCRs), yet physiological roles of such unconventional steroid signaling in controlling alcohol-induced behaviors remain unclear. The dopamine/ecdysteroid receptor (DopEcR) is a GPCR that mediates nongenomic actions of ecdysteroids, the major steroid hormones in insects. Here, we report that Drosophila DopEcR plays a critical role in ethanol-induced sedation.DopEcR mutants took longer than control flies to become sedated during exposure to ethanol, despite having normal ethanol absorption or metabolism. RNAi-mediated knockdown of DopEcR expression revealed that this receptor is necessary after eclosion, and is required in particular neuronal subsets, including cholinergic and peptidergic neurons, to mediate this behavior. Additionally, flies ubiquitously overexpressing DopEcR cDNA had a tendency to become sedated quickly upon ethanol exposure. These results indicate that neuronal subset-specific expression of DopEcR in adults is required for normal sedation upon exposure to ethanol. We also obtained evidence indicating that DopEcR may promote ethanol sedation by suppressing epidermal growth factor receptor/extracellular signal-regulated kinase signaling. Last, genetic and pharmacological analyses suggested that in adult flies ecdysone may serve as an inverse agonist of DopEcR and suppress the sedation-promoting activity of DopEcR in the context of ethanol exposure. Our findings provide the first evidence for the involvement of nongenomic G-protein-coupled steroid receptors in the response to alcohol, and shed new light on the potential roles of steroids in alcohol-use disorders. Alcohol abuse is an alarming personal and societal burden. The improvement of prevention and

  10. The Many Victims of Substance Abuse

    PubMed Central

    2007-01-01

    Substance abuse is a complicated disorder and has far reaching consequences. The victims of substance abuse extend beyond the unfortunate ones suffering from this disorder and often include family and friends. Treatment options for substance abuse are many; however, positive outcomes are not always guaranteed. Many factors play into the potential for successful treatment. Some of these include the adherence and motivation of the substance abusing patients as well as patients' surrounding environments and support systems. In this article, we present a clinical case of opioid dependence and discuss various treatment options and modalities. We will discuss different variables that may maximize positive treatment outcomes. Also a review of the current literature regarding substance abuse treatment, psychotherapy with the drug abuser, and grief therapy should the substance abusing patient die for the surviving family members will be presented. PMID:20532120

  11. Child Abuse and Developmental Disabilities.

    ERIC Educational Resources Information Center

    Grayson, Joann, Ed.; Bartlette, Don

    1992-01-01

    Literature indicating high rates of abuse in this population is reviewed, as is literature indicating high rates of developmental disabilities in child victims of abuse. Problems in data collecting practices are noted. Reasons for these children's greater risk for abuse are identified, including child attributes, stress, parent vulnerabilities,…

  12. PRENATAL ETHANOL EXPOSURE LEADS TO GREATER ETHANOL-INDUCED APPETITIVE REINFORCEMENT

    PubMed Central

    Pautassi, Ricardo M.; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.

    2012-01-01

    Prenatal ethanol significantly heightens later alcohol consumption, but the mechanisms that underlie this phenomenon are poorly understood. Little is known about the basis of this effect of prenatal ethanol on the sensitivity to ethanol’s reinforcing effects. One possibility is that prenatal ethanol exposure makes subjects more sensitive to the appetitive effects of ethanol or less sensitive to ethanol’s aversive consequences. The present study assessed ethanol-induced second-order conditioned place preference (CPP) and aversion and ethanol-induced conditioned taste aversion (CTA) in infant rats prenatally exposed to ethanol (2.0 g/kg) or vehicle (water) or left untreated. The involvement of the κ opioid receptor system in ethanol-induced CTA was also explored. When place conditioning occurred during the ascending limb of the blood-ethanol curve (Experiment 1), the pups exposed to ethanol in utero exhibited greater CPP than untreated controls, with a shift to the right of the dose-response curve. Conditioning during a later phase of intoxication (30–45 min post-administration; Experiment 2) resulted in place aversion in control pups exposed to vehicle during late gestation but not in pups that were exposed to ethanol in utero. Ethanol induced a reliable and similar CTA (Experiment 3) in the pups treated with vehicle or ethanol during gestation, and CTA was insensitive to κ antagonism. These results suggest that brief exposure to a moderate ethanol dose during late gestation promotes ethanol-mediated reinforcement and alters the expression of conditioned aversion by ethanol. This shift in the motivational reactivity to ethanol may be an underlying basis of the effect of prenatal ethanol on later ethanol acceptance. PMID:22698870

  13. Drug Abuse in Southeast Asia.

    ERIC Educational Resources Information Center

    Scorzelli, James F.

    This report examines the incidence of drug abuse and the methods of treatment and prevention of drug abuse used in Southeast Asia. Countries studied include Malaysia, Singapore, Thailand, Indonesia, and the Philippines. Because of Malaysia's intensive effort to eliminate its drug abuse problem, emphasis is placed on this country's treatment and…

  14. Geriatric Alcoholism and Drug Abuse

    ERIC Educational Resources Information Center

    Schuckit, Marc A.

    1977-01-01

    This paper reviews the literature and presents new data on alcohol and drug problems in older individuals. Drug abusers include users of opiates, inadvertent misusers, and deliberate abusers of nonopiates. Two to 10 percent of the elderly are alcoholic, and these are usually individuals beginning alcohol abuse after age 40. (Author)

  15. Effects of repeated cocaine exposure and withdrawal on voluntary ethanol drinking, and the expression of glial glutamate transporters in mesocorticolimbic system of P rats.

    PubMed

    Hammad, Alaa M; Althobaiti, Yusuf S; Das, Sujan C; Sari, Youssef

    2017-07-01

    Glutamatergic neurotransmission within the brain's reward circuits plays a major role in the reinforcing properties of both ethanol and cocaine. Glutamate homeostasis is regulated by several glutamate transporters, including glutamate transporter type 1 (GLT-1), cystine/glutamate transporter (xCT), and glutamate aspartate transporter (GLAST). Cocaine exposure has been shown to induce a dysregulation in glutamate homeostasis and a decrease in the expression of GLT-1 and xCT in the nucleus accumbens (NAc). In this study, alcohol preferring (P) rats were exposed to free-choice of ethanol (15% and 30%) and/or water for five weeks. On Week 6, rats were administered (i.p.) cocaine (10 and 20mg/kg) or saline for 12 consecutive days. This study tested two groups of rats: the first group was euthanized after seven days of repeated cocaine i.p. injection, and the second group was deprived from cocaine for five days and euthanized at Day 5 after cocaine withdrawal. Only repeated cocaine (20mg/kg, i.p.) exposure decreased ethanol intake from Day 3 through Day 8. Co-exposure of cocaine and ethanol decreased the relative mRNA expression and the expression of GLT-1 in the NAc but not in the medial prefrontal cortex (mPFC). Importantly, co-exposure of cocaine and ethanol decreased relative expression of xCT in the NAc but not in the mPFC. Our findings demonstrated that chronic cocaine exposure affects ethanol intake; and ethanol and cocaine co-abuse alters the expression of glial glutamate transporters. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Study of acetylcholinesterase activity and apoptosis in SH-SY5Y cells and mice exposed to ethanol.

    PubMed

    Sun, Wenjun; Chen, Liangjing; Zheng, Wei; Wei, Xiaoan; Wu, Wenqi; Duysen, Ellen G; Jiang, Wei

    2017-06-01

    Ethanol is one of the most commonly abused psychotropic substances with deleterious effects on the central nervous system. Ethanol exposure during development results in the loss of neurons in brain regions and when exposed to ethanol cultured cells undergo apoptosis. To date no information is available on whether abnormally high AChE activity is characteristic of apoptosis in animals exposed to ethanol. The aims of the present study were to determine whether induction of AChE activity is associated with ethanol-induced apoptosis and to explore the mechanism of enhanced AChE activity induced by ethanol. For this purpose, in vitro and in vivo experiments were performed. AChE activity was quantified by spectrophotometry and apoptosis by flow cytometer in SH-SY5Y cells exposed to ethanol. The results showed that cells treated with 500mM ethanol for 24h had a 9-fold increase in apoptotic cells and a 6-fold increase in AChE activity compared with controls. Mice exposed acutely to 200μl of 20% ethanol daily on days 1-4 had elevated AChE activity in plasma on days 3-7. On day 4, plasma AChE activity was 2.4-fold higher than pretreatment activity. More apoptotic cells were found in the brains of treated mice compared to controls. Cells in brain sections that were positive in the TUNEL assay stained for AChE activity. In conclusion, AChE activity and apoptosis were induced in SH-SY5Y cells and mice treated with ethanol, which may indicate that increased AChE may related to apoptosis induced by ethanol. Unusually high AChE activity may be an effect marker of exposure to ethanol. The relationship between AChE and apoptosis might represent a novel mechanism of ethanol-associated neuronal injury. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

    PubMed Central

    Navarro-Zaragoza, Javier; Ros-Simó, Clara; Milanés, María-Victoria; Valverde, Olga; Laorden, María-Luisa

    2015-01-01

    Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA). The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27), after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA). Drinking in the dark (DID) procedure was used as a model of binge. Noradrenaline (NA) turnover, tyrosine hydroxylase (TH), TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN) were determined by high-performance liquid chromatography (HPLC); TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone. PMID:26509576

  18. Extrasynaptic Glycine Receptors of Rodent Dorsal Raphe Serotonergic Neurons: A Sensitive Target for Ethanol

    PubMed Central

    Maguire, Edward P; Mitchell, Elizabeth A; Greig, Scott J; Corteen, Nicole; Balfour, David J K; Swinny, Jerome D; Lambert, Jeremy J; Belelli, Delia

    2014-01-01

    Alcohol abuse is a significant medical and social problem. Several neurotransmitter systems are implicated in ethanol's actions, with certain receptors and ion channels emerging as putative targets. The dorsal raphe (DR) nucleus is associated with the behavioral actions of alcohol, but ethanol actions on these neurons are not well understood. Here, using immunohistochemistry and electrophysiology we characterize DR inhibitory transmission and its sensitivity to ethanol. DR neurons exhibit inhibitory ‘phasic' post-synaptic currents mediated primarily by synaptic GABAA receptors (GABAAR) and, to a lesser extent, by synaptic glycine receptors (GlyR). In addition to such phasic transmission mediated by the vesicular release of neurotransmitter, the activity of certain neurons may be governed by a ‘tonic' conductance resulting from ambient GABA activating extrasynaptic GABAARs. However, for DR neurons extrasynaptic GABAARs exert only a limited influence. By contrast, we report that unusually the GlyR antagonist strychnine reveals a large tonic conductance mediated by extrasynaptic GlyRs, which dominates DR inhibition. In agreement, for DR neurons strychnine increases their input resistance, induces membrane depolarization, and consequently augments their excitability. Importantly, this glycinergic conductance is greatly enhanced in a strychnine-sensitive fashion, by behaviorally relevant ethanol concentrations, by drugs used for the treatment of alcohol withdrawal, and by taurine, an ingredient of certain ‘energy drinks' often imbibed with ethanol. These findings identify extrasynaptic GlyRs as critical regulators of DR excitability and a novel molecular target for ethanol. PMID:24264816

  19. Protracted ethanol withdrawal in rats: Tolerance to the anxiolytic effects of diazepam and pentobarbital but not phenobarbital

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

    Lai, H.; Prather, P.L.

    1990-02-26

    Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats weremore » trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ethanol diet, rats exhibited signs and symptoms of withdrawal which returned to baseline within 3 days. During the protracted withdrawal period, the authors then redetermined the blockade of the PTZ-IDS. Significant tolerance was observed to the effectiveness of diazepam and pentobarbital, but not to phenobarbital. Since diazepam and pentobarbital produce significantly more enhancement of GABAergic activity than does phenobarbital, these data further suggest alteration of brain GABAergic systems during protracted withdrawal from ethanol.« less

  20. Determine new design and construction techniques for transportation of ethanol and ethanol/gasoline blends in new pipelines.

    DOT National Transportation Integrated Search

    2013-02-15

    The technical tasks in this study included activities to characterize the impact of selected : metallurgical processing and fabrication variables on ethanol stress corrosion cracking (ethanol : SCC) of new pipeline steels, develop a better understand...

  1. Quantitative trait loci for response to ethanol in an intercontinental set of recombinant inbred lines of Drosophila melanogaster.

    PubMed

    Defays, Raquel; Bertoli, Carlos Ignacio

    2012-12-01

    Alcohol, a drug widely abused, impacts the central nervous system functioning of diverse organisms. The behavioral responses to acute alcohol exposure are remarkably similar among humans and fruit flies. In its natural environment, rich in fermentation products, the fruit fly Drosophila melanogaster encounters relatively high levels of ethanol. The effects of ethanol and its metabolites on Drosophila have been studied for decades, as a model for adaptive evolution. Although extensive work has been done for elucidating patterns of genetic variation, substantially less is known about the genomic regions or genes that underlie the genetic variation of this important trait. To identify regions containing genes involved in the responses to ethanol, we used a mapping population of recombinant inbred (RIL) lines to map quantitative trait loci (QTL) that affect variation in resistance and recovery from ethanol sedation in adults and ethanol resistance in larvae. We mapped fourteen QTL affecting the response to ethanol on the three chromosomes. Seven of the QTL influence the resistance to ethanol in adults, two QTL are related to ethanol-coma recovery in adults and five affect the survival to ethanol in larvae. Most of the QTL were trait specific, suggesting that overlapping but generally unique genetic architectures underlie each trait. Each QTL explained up to 16.8% of the genetic variance among lines. Potential candidate loci contained within our QTL regions were identified and analyzed. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. The bed nucleus of the stria terminalis regulates ethanol-seeking behavior in mice.

    PubMed

    Pina, Melanie M; Young, Emily A; Ryabinin, Andrey E; Cunningham, Christopher L

    2015-12-01

    Drug-associated stimuli are considered important factors in relapse to drug use. In the absence of drug, these cues can trigger drug craving and drive subsequent drug seeking. One structure that has been implicated in this process is the bed nucleus of the stria terminalis (BNST), a chief component of the extended amygdala. Previous studies have established a role for the BNST in cue-induced cocaine seeking. However, it is unclear if the BNST underlies cue-induced seeking of other abused drugs such as ethanol. In the present set of experiments, BNST involvement in ethanol-seeking behavior was assessed in male DBA/2J mice using the conditioned place preference procedure (CPP). The BNST was inhibited during CPP expression using electrolytic lesions (Experiment 1), co-infusion of GABAA and GABAB receptor agonists muscimol and baclofen (M+B; Experiment 2), and activation of inhibitory designer receptors exclusively activated by designer drugs (hM4Di-DREADD) with clozapine-N-oxide (CNO; Experiment 3). The magnitude of ethanol CPP was reduced significantly by each of these techniques. Notably, infusion of M+B (Exp. 2) abolished CPP altogether. Follow-up studies to Exp. 3 showed that ethanol cue-induced c-Fos immunoreactivity in the BNST was reduced by hM4Di activation (Experiment 4) and in the absence of hM4Di, CNO did not affect ethanol CPP (Experiment 5). Combined, these findings demonstrate that the BNST is involved in the modulation of cue-induced ethanol-seeking behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Electrocatalysis of anodic oxidation of ethanol

    NASA Astrophysics Data System (ADS)

    Tarasevich, M. R.; Korchagin, O. V.; Kuzov, A. V.

    2013-11-01

    The results of fundamental and applied studies in the field of electrocatalysis of anodic oxidation of ethanol in fuel cells are considered. Features of the mechanism of ethanol electrooxidation are discussed as well as the structure and electrochemical properties of the most widely used catalysts of this process. The prospects of further studies of direct ethanol fuel cells with alkaline and acidic electrolytes are outlined. The bibliography includes 166 references.

  4. Substance abuse and child maltreatment.

    PubMed

    Wells, Kathryn

    2009-04-01

    Pediatricians and other medical providers caring for children need to be aware of the dynamics in the significant relationship between substance abuse and child maltreatment. A caregiver's use and abuse of alcohol, marijuana, heroin, cocaine, methamphetamine, and other drugs place the child at risk in multiple ways. Members of the medical community need to understand these risks because the medical community plays a unique and important role in identifying and caring for these children. Substance abuse includes the abuse of legal drugs as well as the use of illegal drugs. The abuse of legal substances may be just as detrimental to parental functioning as abuse of illicit substances. Many substance abusers are also polysubstance users and the compounded effect of the abuse of multiple substances may be difficult to measure. Often other interrelated social features, such as untreated mental illness, trauma history, and domestic violence, affect these families.

  5. A Quantitative Gas Chromatographic Ethanol Determination.

    ERIC Educational Resources Information Center

    Leary, James J.

    1983-01-01

    Describes a gas chromatographic experiment for the quantitative determination of volume percent ethanol in water ethanol solutions. Background information, procedures, and typical results are included. Accuracy and precision of results are both on the order of two percent. (JN)

  6. Sorghum to Ethanol Research

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

    Dahlberg, Jeffrey A.; Wolfrum, Edward J.

    2010-09-28

    The development of a robust source of renewable transportation fuel will require a large amount of biomass feedstocks. It is generally accepted that in addition to agricultural and forestry residues, we will need crops grown specifically for subsequent conversion into fuels. There has been a lot of research on several of these so-called "dedicated bioenergy crops" including switchgrass, miscanthus, sugarcane, and poplar. It is likely that all of these crops will end up playing a role as feedstocks, depending on local environmental and market conditions. Many different types of sorghum have been grown to produce syrup, grain, and animal feedmore » for many years. It has several features that may make it as compelling as other crops mentioned above as a renewable, sustainable biomass feedstock; however, very little work has been done to investigate sorghum as a dedicated bioenergy crop. The goal of this project was to investigate the feasibility of using sorghum biomass to produce ethanol. The work performed included a detailed examination of the agronomics and composition of a large number of sorghum varieties, laboratory experiments to convert sorghum to ethanol, and economic and life-cycle analyses of the sorghum-to-ethanol process. This work showed that sorghum has a very wide range of composition, which depended on the specific sorghum cultivar as well as the growing conditions. The results of laboratory- and pilot-scale experiments indicated that a typical high-biomass sorghum variety performed very similarly to corn stover during the multi-step process required to convert biomass feedstocks to ethanol; yields of ethanol for sorghum were very similar to the corn stover used as a control in these experiments. Based on multi-year agronomic data and theoretical ethanol production, sorghum can achieve more than 1,300 gallons of ethanol per acre given the correct genetics and environment. In summary, sorghum may be a compelling dedicated bioenergy crop that could

  7. Operant ethanol self-administration in ethanol dependent mice.

    PubMed

    Lopez, Marcelo F; Becker, Howard C

    2014-05-01

    While rats have been predominantly used to study operant ethanol self-administration behavior in the context of dependence, several studies have employed operant conditioning procedures to examine changes in ethanol self-administration behavior as a function of chronic ethanol exposure and withdrawal experience in mice. This review highlights some of the advantages of using operant conditioning procedures for examining the motivational effects of ethanol in animals with a history of dependence. As reported in rats, studies using various operant conditioning procedures in mice have demonstrated significant escalation of ethanol self-administration behavior in mice rendered dependent via forced chronic ethanol exposure in comparison to nondependent mice. This paper also presents a summary of these findings, as well as suggestions for future studies. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Comparative and network-based proteomic analysis of low dose ethanol- and lipopolysaccharide-induced macrophages.

    PubMed

    Kamal, Abu Hena M; Fessler, Michael B; Chowdhury, Saiful M

    2018-01-01

    Macrophages are specialized phagocytes that play an essential role in inflammation, immunity, and tissue repair. Profiling the global proteomic response of macrophages to microbial molecules such as bacterial lipopolysaccharide is key to understanding fundamental mechanisms of inflammatory disease. Ethanol is a widely abused substance that has complex effects on inflammation. Reports have indicated that ethanol can activate or inhibit the lipopolysaccharide receptor, Toll-like Receptor 4, in different settings, with important consequences for liver and neurologic inflammation, but the underlying mechanisms are poorly understood. To profile the sequential effect of low dose ethanol and lipopolysaccharide on macrophages, a gel-free proteomic technique was applied to RAW 264.7 macrophages. Five hundred four differentially expressed proteins were identified and quantified with high confidence using ≥ 5 peptide spectral matches. Among these, 319 proteins were shared across all treatment conditions, and 69 proteins were exclusively identified in ethanol-treated or lipopolysaccharide-stimulated cells. The interactive impact of ethanol and lipopolysaccharide on the macrophage proteome was evaluated using bioinformatics tools, enabling identification of differentially responsive proteins, protein interaction networks, disease- and function-based networks, canonical pathways, and upstream regulators. Five candidate protein coding genes (PGM2, ISYNA1, PARP1, and PSAP) were further validated by qRT-PCR that mostly related to glucose metabolism and fatty acid synthesis pathways. Taken together, this study describes for the first time at a systems level the interaction between ethanol and lipopolysaccharide in the proteomic programming of macrophages, and offers new mechanistic insights into the biology that may underlie the impact of ethanol on infectious and inflammatory disease in humans.

  9. Comparative and network-based proteomic analysis of low dose ethanol- and lipopolysaccharide-induced macrophages

    PubMed Central

    Kamal, Abu Hena M.; Fessler, Michael B.

    2018-01-01

    Macrophages are specialized phagocytes that play an essential role in inflammation, immunity, and tissue repair. Profiling the global proteomic response of macrophages to microbial molecules such as bacterial lipopolysaccharide is key to understanding fundamental mechanisms of inflammatory disease. Ethanol is a widely abused substance that has complex effects on inflammation. Reports have indicated that ethanol can activate or inhibit the lipopolysaccharide receptor, Toll-like Receptor 4, in different settings, with important consequences for liver and neurologic inflammation, but the underlying mechanisms are poorly understood. To profile the sequential effect of low dose ethanol and lipopolysaccharide on macrophages, a gel-free proteomic technique was applied to RAW 264.7 macrophages. Five hundred four differentially expressed proteins were identified and quantified with high confidence using ≥ 5 peptide spectral matches. Among these, 319 proteins were shared across all treatment conditions, and 69 proteins were exclusively identified in ethanol-treated or lipopolysaccharide-stimulated cells. The interactive impact of ethanol and lipopolysaccharide on the macrophage proteome was evaluated using bioinformatics tools, enabling identification of differentially responsive proteins, protein interaction networks, disease- and function-based networks, canonical pathways, and upstream regulators. Five candidate protein coding genes (PGM2, ISYNA1, PARP1, and PSAP) were further validated by qRT-PCR that mostly related to glucose metabolism and fatty acid synthesis pathways. Taken together, this study describes for the first time at a systems level the interaction between ethanol and lipopolysaccharide in the proteomic programming of macrophages, and offers new mechanistic insights into the biology that may underlie the impact of ethanol on infectious and inflammatory disease in humans. PMID:29481576

  10. Do abuse deterrent opioid formulations work?

    PubMed

    Dart, Richard C; Iwanicki, Janetta L; Dasgupta, Nabarun; Cicero, Theodore J; Schnoll, Sidney H

    We performed a systematic review to answer the question, "Does the introduction of an opioid analgesic with abuse deterrent properties result in reduced overall abuse of the drug in the community?" We included opioid analgesics with abuse deterrent properties (hydrocodone, morphine, oxycodone) with results restricted to the metasearch term "delayed onset," English language, use in humans, and publication years 2009-2016. All articles that contained data evaluating misuse, abuse, overdose, addiction, and death were included. The results were categorized using the Bradford-Hill criteria. We included 44 reports: hydrocodone (n = 7), morphine (n = 5), or oxycodone (n = 32) with Food and Drug Administration-approved Categories 1, 2, or 3 abuse deterrent labeling. The data currently available support the Hill criteria of strength (effect size), consistency (reproducibility), temporality, plausibility, and coherence. There was insufficient or no information available for the criteria of biological gradient, experiment, and analogy. We also assessed confounding factors and bias, which indicated that both were present and substantial in magnitude. Our analysis found that only oxycodone extended release (ER) had information available to evaluate abuse deterrence in the community. In Australia, Canada, and the United States, reformulation of oxycodone ER was followed by marked reduction in measures of abuse. The precise extent of reduced abuse cannot be calculated because of heterogeneous data sets, but the reported reductions ranged from 10 to 90 percent depending on the measure and the duration of follow-up.

  11. Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats

    PubMed Central

    Miranda-Morales, Roberto Sebastián; Nizhnikov, Michael E.; Spear, Norman E.

    2014-01-01

    Prenatal ethanol exposure modifies postnatal affinity to the drug, increasing the probability of ethanol use and abuse. The present study tested developing rats (5-day-old) in a novel operant technique to assess the degree of ethanol self-administration as a result of prenatal exposure to low ethanol doses during late gestation. On a single occasion during each of gestational days 17–20, pregnant rats were intragastrically administered ethanol 1 g/kg, or water (vehicle). On postnatal day 5, pups were tested on a novel operant conditioning procedure in which they learned to touch a sensor to obtain 0.1% saccharin, 3% ethanol, or 5% ethanol. Immediately after a 15-min training session, a 6-min extinction session was given in which operant behavior had no consequence. Pups were positioned on a smooth surface and had access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump, which served to deliver an intraoral solution as reinforcement (Paired group). A Yoked control animal evaluated at the same time received the reinforcer when its corresponding Paired pup touched the sensor. Operant behavior to gain access to 3% ethanol was facilitated by prenatal exposure to ethanol during late gestation. In contrast, operant learning reflecting ethanol reinforcement did not occur in control animals prenatally exposed to water only. Similarly, saccharin reinforcement was not affected by prenatal ethanol exposure. These results suggest that in 5-day-old rats, prenatal exposure to a low ethanol dose facilitates operant learning reinforced by intraoral administration of a low-concentration ethanol solution. This emphasizes the importance of intrauterine experiences with ethanol in later susceptibility to drug reinforcement. The present operant conditioning technique represents an alternative tool to assess self-administration and seeking behavior during early stages of development. PMID:24355072

  12. Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats.

    PubMed

    Miranda-Morales, Roberto Sebastián; Nizhnikov, Michael E; Spear, Norman E

    2014-02-01

    Prenatal ethanol exposure modifies postnatal affinity to the drug, increasing the probability of ethanol use and abuse. The present study tested developing rats (5-day-old) in a novel operant technique to assess the degree of ethanol self-administration as a result of prenatal exposure to low ethanol doses during late gestation. On a single occasion during each of gestational days 17-20, pregnant rats were intragastrically administered ethanol 1 g/kg, or water (vehicle). On postnatal day 5, pups were tested on a novel operant conditioning procedure in which they learned to touch a sensor to obtain 0.1% saccharin, 3% ethanol, or 5% ethanol. Immediately after a 15-min training session, a 6-min extinction session was given in which operant behavior had no consequence. Pups were positioned on a smooth surface and had access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump, which served to deliver an intraoral solution as reinforcement (Paired group). A Yoked control animal evaluated at the same time received the reinforcer when its corresponding Paired pup touched the sensor. Operant behavior to gain access to 3% ethanol was facilitated by prenatal exposure to ethanol during late gestation. In contrast, operant learning reflecting ethanol reinforcement did not occur in control animals prenatally exposed to water only. Similarly, saccharin reinforcement was not affected by prenatal ethanol exposure. These results suggest that in 5-day-old rats, prenatal exposure to a low ethanol dose facilitates operant learning reinforced by intraoral administration of a low-concentration ethanol solution. This emphasizes the importance of intrauterine experiences with ethanol in later susceptibility to drug reinforcement. The present operant conditioning technique represents an alternative tool to assess self-administration and seeking behavior during early stages of development. Published by Elsevier Inc.

  13. Modulation of BK channels by ethanol

    PubMed Central

    Dopico, Alex M.; Bukiya, Anna N.; Kuntamallappanavar, Guruprasad; Liu, Jianxi

    2017-01-01

    In alcohol-naïve systems, ethanol (<100 mM) exposure of calcium-gated BK channels perturbs physiology and behavior. Brief (several minutes) ethanol exposure usually leads to increased BK current, which results from ethanol interaction with a pocket mapped to the BK channel-forming slo1 protein cytosolic tail domain. The importance of this region in alcohol-induced intoxication has been addressed in Caenorhabditis elegans slo1 mutants. However, ethanol-induced BK activation is not universal as refractoriness and inhibition have been reported. The final effect depends on many factors, including intracellular calcium levels, slo1 isoform, BK beta subunit composition, post-translational modification of BK proteins, channel lipid microenvironment and type of ethanol administration. Studies in Drosophila melanogaster, Caenorhabditis elegans and rodents show that protracted/repeated ethanol administration leads to tolerance to alcohol-induced modification of BK-driven physiology and behavior. Unveiling the mechanisms underlying tolerance is of major importance, as tolerance to alcohol has been proposed as predictor of risk for alcoholism. PMID:27238266

  14. Caffeinated Alcoholic Beverages – An Emerging Trend in Alcohol Abuse

    PubMed Central

    Franklin, Kelle M; Hauser, Sheketha R; Bell, Richard L.; Engleman, Eric A

    2014-01-01

    Alcohol use disorders are pervasive in society and their impact affects quality of life, morbidity and mortality, as well as individual productivity. Alcohol has detrimental effects on an individual’s physiology and nervous system, and is associated with disorders of many organ and endocrine systems impacting an individual’s health, behavior, and ability to interact with others. Youth are particularly affected. Unfortunately, adolescent usage also increases the probability for a progression to dependence. Several areas of research indicate that the deleterious effects of alcohol abuse may be exacerbated by mixing caffeine with alcohol. Some behavioral evidence suggests that caffeine increases alcohol drinking and binge drinking episodes, which in turn can foster the development of alcohol dependence. As a relatively new public health concern, the epidemiological focus has been to establish a need for investigating the effects of caffeinated alcohol. While the trend of co-consuming these substances is growing, knowledge of the central mechanisms associated with caffeinated ethanol has been lacking. Research suggests that caffeine and ethanol can have additive or synergistic pharmacological actions and neuroadaptations, with the adenosine and dopamine systems in particular implicated. However, the limited literature on the central effects of caffeinated ethanol provides an impetus to increase our knowledge of the neuroadaptive effects of this combination and their impact on cognition and behavior. Research from our laboratories indicates that an established rodent animal model of alcoholism can be extended to investigate the acute and chronic effects of caffeinated ethanol. PMID:25419478

  15. Interventions for preventing abuse in the elderly.

    PubMed

    Baker, Philip R A; Francis, Daniel P; Hairi, Noran N; Othman, Sajaratulnisah; Choo, Wan Yuen

    2016-08-16

    Maltreatment of older people (elder abuse) includes psychological, physical, sexual abuse, neglect and financial exploitation. Evidence suggests that 10% of older adults experience some form of abuse, and only a fraction of cases are actually reported or referred to social services agencies. Elder abuse is associated with significant morbidity and premature mortality. Numerous interventions have been implemented to address the issue of elder maltreatment. It is, however, unclear which interventions best serve to prevent or reduce elder abuse. The objective of this review was to assess the effectiveness of primary, secondary and tertiary intervention programmes used to reduce or prevent abuse of the elderly in their own home, in organisational or institutional and community settings. The secondary objective was to investigate whether intervention effects are modified by types of abuse, types of participants, setting of intervention, or the cognitive status of older people. We searched 19 databases (AgeLine, CINAHL, Psycinfo, MEDLINE, Embase, Proquest Central, Social Services Abstracts‎, ASSIA, Sociological Abstracts, ProQuest Dissertations & Theses Global, Web of Science, LILACS, EPPI, InfoBase, CENTRAL, HMIC, Opengrey and Zetoc) on 12 platforms, including multidisciplinary disciplines covering medical, health, social sciences, social services, legal, finance and education. We also browsed related organisational websites, contacted authors of relevant articles and checked reference lists. Searches of databases were conducted between 30 August 2015 and 16 March 2016 and were not restricted by language. We included randomised controlled trials (RCTs), cluster-randomised trials, and quasi-RCTs, before-and-after studies, and interrupted time series. Only studies with at least 12 weeks of follow-up investigating the effect of interventions in preventing or reducing abuse of elderly people and those who interact with the elderly were included. Two review authors

  16. Autophagy protects gastric mucosal epithelial cells from ethanol-induced oxidative damage via mTOR signaling pathway

    PubMed Central

    Chang, Weilong; Bai, Jie; Tian, Shaobo; Ma, Muyuan; Li, Wei; Yin, Yuping; Deng, Rui; Cui, Jinyuan; Li, Jinjin; Wang, Guobin; Tao, Kaixiong

    2017-01-01

    Alcohol abuse is an important cause of gastric mucosal epithelial cell injury and gastric ulcers. A number of studies have demonstrated that autophagy, an evolutionarily conserved cellular mechanism, has a protective effect on cell survival. However, it is not known whether autophagy can protect gastric mucosal epithelial cells against the toxic effects of ethanol. In the present study, gastric mucosal epithelial cells (GES-1 cells) and Wistar rats were treated with ethanol to detect the adaptive response of autophagy. Our results demonstrated that ethanol exposure induced gastric mucosal epithelial cell damage, which was accompanied by the downregulation of mTOR signaling pathway and activation of autophagy. Suppression of autophagy with pharmacological agents resulted in a significant increase of GES-1 cell apoptosis and gastric mucosa injury, suggesting that autophagy could protect cells from ethanol toxicity. Furthermore, we evaluated the cellular oxidative stress response following ethanol treatment and found that autophagy induced by ethanol inhibited generation of reactive oxygen species and degradation of antioxidant and lipid peroxidation. In conclusion, these findings provide evidence that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate oxidative damage induced by ethanol in gastric mucosal epithelial cells. Therefore, modifying autophagy may provide a therapeutic strategy against alcoholic gastric mucosa injury. Impact statement The effect and mechanism of autophagy on ethanol-induced cell damage remain controversial. In this manuscript, we report the results of our study demonstrating that autophagy can protect gastric mucosal epithelial cells against ethanol toxicity in vitro and in vivo. We have shown that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate ethanol-induced oxidative damage in

  17. High ethanol producing derivatives of Thermoanaerobacter ethanolicus

    DOEpatents

    Ljungdahl, L.G.; Carriera, L.H.

    1983-05-24

    Derivatives of the newly discovered microorganism Thermoanaerobacter ethanolicus which under anaerobic and thermophilic conditions continuously ferment substrates such as starch, cellobiose, glucose, xylose and other sugars to produce recoverable amounts of ethanol solving the problem of fermentations yielding low concentrations of ethanol using the parent strain of the microorganism Thermoanaerobacter ethanolicus are disclosed. These new derivatives are ethanol tolerant up to 10% (v/v) ethanol during fermentation. The process includes the use of an aqueous fermentation medium, containing the substrate at a substrate concentration greater than 1% (w/v).

  18. High ethanol producing derivatives of Thermoanaerobacter ethanolicus

    DOEpatents

    Ljungdahl, Lars G.; Carriera, Laura H.

    1983-01-01

    Derivatives of the newly discovered microorganism Thermoanaerobacter ethanolicus which under anaerobic and thermophilic conditions continuously ferment substrates such as starch, cellobiose, glucose, xylose and other sugars to produce recoverable amounts of ethanol solving the problem of fermentations yielding low concentrations of ethanol using the parent strain of the microorganism Thermoanaerobacter ethanolicus are disclosed. These new derivatives are ethanol tolerant up to 10% (v/v) ethanol during fermentation. The process includes the use of an aqueous fermentation medium, containing the substrate at a substrate concentration greater than 1% (w/v).

  19. KINETICS OF ETHANOL BIODEGRADATION UNDER METHANOGENIC CONDITIONS IN GASOLINE SPILLS

    EPA Science Inventory

    Ethanol is commonly used as a fuel oxygenate. A concern has been raised that biodegradation of ethanol from a spill of gasoline may inhibit the natural biodegradation of fuel hydrocarbons, including benzene. Ethanol is miscible in water, and ethanol is readily metabolized by mi...

  20. EFFECT OF ETHANOL ON THE NATURAL ANAEROBIC BIODEGRADATION OF BENZENE

    EPA Science Inventory

    Ethanol is commonly used as a fuel oxygenate. A concern has been raised that the presence of ethanol from a spill of gasoline may inhibit the natural biodegradation of fuel hydrocarbons, including benzene. Ethanol is miscible in water, and ethanol is readily metabolized by micr...

  1. Changes in the female arcuate nucleus morphology and neurochemistry after chronic ethanol consumption and long-term withdrawal.

    PubMed

    Rebouças, Elce C C; Leal, Sandra; Silva, Susana M; Sá, Susana I

    2016-11-01

    Ethanol is a macronutrient whose intake is a form of ingestive behavior, sharing physiological mechanisms with food intake. Chronic ethanol consumption is detrimental to the brain, inducing gender-dependent neuronal damage. The hypothalamic arcuate nucleus (ARN) is a modulator of food intake that expresses feeding-regulatory neuropeptides, such as alpha melanocyte-stimulating hormone (α-MSH) and neuropeptide Y (NPY). Despite its involvement in pathways associated with eating disorders and ethanol abuse, the impact of ethanol consumption and withdrawal in the ARN structure and neurochemistry in females is unknown. We used female rat models of 20% ethanol consumption for six months and of subsequent ethanol withdrawal for two months. Food intake and body weights were measured. ARN morphology was stereologically analyzed to estimate its volume, total number of neurons and total number of neurons expressing NPY, α-MSH, tyrosine hydroxylase (TH) and estrogen receptor alpha (ERα). Ethanol decreased energy intake and body weights. However, it did not change the ARN morphology or the expression of NPY, α-MSH and TH, while increasing ERα expression. Withdrawal induced a significant volume and neuron loss that was accompanied by an increase in NPY expression without affecting α-MSH and TH expression. These findings indicate that the female ARN is more vulnerable to withdrawal than to excess alcohol. The data also support the hypothesis that the same pathways that regulate the expression of NPY and α-MSH in long-term ethanol intake may regulate food intake. The present model of long-term ethanol intake and withdrawal induces new physiological conditions with adaptive responses. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Michigan Physicians' Conference on Elder Abuse. Final Report.

    ERIC Educational Resources Information Center

    Sengstock, Mary C.; O'Brien, James G.

    The final report describes the Michigan Physicians' Conference on Elder Abuse project. The project conference had four major content areas, including: a general introduction to the problem of elder abuse; clinical symptoms of abuse; legal issues; and referral and case management techniques. Training techniques included lectures, group discussion,…

  3. Persistent escalation of alcohol drinking in C57BL/6J mice with intermittent access to 20% ethanol.

    PubMed

    Hwa, Lara S; Chu, Adam; Levinson, Sally A; Kayyali, Tala M; DeBold, Joseph F; Miczek, Klaus A

    2011-11-01

    Intermittent access (IA) to drugs of abuse, as opposed to continuous access, is hypothesized to induce a kindling-type transition from moderate to escalated use, leading to dependence. Intermittent 24-hour cycles of ethanol access and deprivation can generate high levels of voluntary ethanol drinking in rats. The current study uses C57BL/6J mice (B6) in an IA to 20% ethanol protocol to escalate ethanol drinking levels. Adult male and female B6 mice were given IA to 20% ethanol on alternating days of the week with water available ad libitum. Ethanol consumption during the initial 2 hours of access was compared with a short-term, limited access "binge" drinking procedure, similar to drinking-in-the-dark (DID). B6 mice were also assessed for ethanol dependence with handling-induced convulsion, a reliable measure of withdrawal severity. After 3 weeks, male mice given IA to ethanol achieved high stable levels of ethanol drinking in excess of 20 g/kg/24 h, reaching above 100 mg/dl blood ethanol concentrations, and showed a significantly higher ethanol preference than mice given continuous access to ethanol. Also, mice given IA drank about twice as much as DID mice in the initial 2-hour access period. B6 mice that underwent the IA protocol for longer periods of time displayed more severe signs of alcohol withdrawal. Additionally, female B6 mice were given IA to ethanol and drank significantly more than males (ca. 30 g/kg/24 h). The IA method in B6 mice is advantageous because it induces escalated, voluntary, and preferential per os ethanol intake, behavior that may mimic a cardinal feature of human alcohol dependence, though the exact nature and site of ethanol acting in the brain and blood as a result of IA has yet to be determined. Copyright © 2011 by the Research Society on Alcoholism.

  4. Substance Abuse and Counseling: An Epilogue.

    ERIC Educational Resources Information Center

    Sales, Amos

    This chapter discusses current issues and future perspectives in relation to substance abuse counseling. Current issues include: abstinence versus controlled use; coercive versus voluntary treatment; and career development and counseling with clients with substance abuse problems. Future perspectives include: the impact of managed care; the…

  5. Innate BDNF expression is associated with ethanol intake in alcohol-preferring AA and alcohol-avoiding ANA rats.

    PubMed

    Raivio, Noora; Miettinen, Pekka; Kiianmaa, Kalervo

    2014-09-04

    We have shown recently that acute administration of ethanol modulates the expression of brain-derived neurotrophic factor (BDNF) in several rat brain areas known to be involved in the development of addiction to ethanol and other drugs of abuse, suggesting that BDNF may be a factor contributing to the neuroadaptive changes set in motion by ethanol exposure. The purpose of the present study was to further clarify the role of BDNF in reinforcement from ethanol and in the development of addiction to ethanol by specifying the effect of acute administration of ethanol (1.5 or 3.0 g/kg i.p.) on the expression profile of BDNF mRNA in the ventral tegmental area and in the terminal areas of the mesolimbic dopamine pathway in the brain of alcohol-preferring AA and alcohol-avoiding ANA rats, selected for high and low voluntary ethanol intake, respectively. The level of BDNF mRNA expression was higher in the amygdala and ventral tegmental area of AA than in those of ANA rats, and there was a trend for a higher level in the nucleus accumbens. In the amygdala and hippocampus, a biphasic change in the BDNF mRNA levels was detected: the levels were decreased at 3 and 6h but increased above the basal levels at 24h. Furthermore, there was a difference between the AA and ANA lines in the effect of ethanol, the ANA rats showing an increase in BDNF mRNA levels while such a change was not seen in AA rats. These findings suggest that the innate levels of BDNF expression may play a role in the mediation of the reinforcing effects of ethanol and in the control of ethanol intake. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Social opportunity and ethanol drinking in rats.

    PubMed

    Tomie, Arthur; Burger, Kelly M; Di Poce, Jason; Pohorecky, Larissa A

    2004-11-01

    Two experiments were designed to evaluate the effects of pairings of ethanol sipper conditioned stimulus (CS) with social opportunity unconditioned stimulus (US) on ethanol sipper CS-directed drinking in rats. In both experiments, rats were deprived of neither food nor water, and initiation of drinking of unsweetened 3% ethanol was evaluated, as were the effects of increasing the concentration of unsweetened ethanol (3-10%) across sessions. In Experiment 1, Group Paired (n=8) received 35 trials per session wherein the ethanol sipper CS was presented for 10 s immediately prior to 15 s of social opportunity US. All rats initiated sipper CS-directed drinking of 3% ethanol. Increasing the concentration of ethanol in the sipper CS [(3%, 4%, 6%, 8%, 10% (vol./vol.)] across sessions induced escalation of daily g/kg ethanol intake. To evaluate the hypothesis that the drinking in Group Paired was due to autoshaping, Experiment 2 included a pseudoconditioning control that received sipper CS and social opportunity US randomly with respect to one another. All rats in Group Paired (n=6) and in Group Random (n=6) initiated sipper CS-directed drinking of 3% ethanol and daily mean g/kg ethanol intake in the two groups was comparable. Also comparable was daily g/kg ethanol intake, which increased for both groups with the availability of higher concentrations of ethanol in the sipper CS, up to a maximum of approximately 0.8 g/kg ethanol intake of 10% ethanol. Results indicate that random presentations of ethanol sipper CS and social opportunity US induced reliable initiation and escalation of ethanol intake, and close temporally contiguous presentations of CS and US did not induce still additional ethanol intake. This may indicate that autoshaping CR performance is not induced by these procedures, or that high levels of ethanol intake induced by factors related to pseudoconditioning produces a ceiling effect. Implications for ethanol drinking in humans are discussed.

  7. Abuse-resistant drug delivery.

    PubMed

    DuPont, Robert L; Bensinger, Peter B

    2006-08-01

    In attempting to reduce the nonmedical use of controlled substances, a reasonable step is to educate the physicians prescribing controlled substances, including the prescription stimulants used to treat ADHD, as well as patients and family members, about the risks of nonmedical use and the dangers of giving or selling these medicines to persons for whom they were not prescribed. Patients who find benefits in the use of such medicines have a significant interest in protecting their continued access to them. Such access is potentially threatened by concerns about widespread nonmedical use. Physicians can help protect the appropriate medical use of prescription stimulants by considering the abuse potential of various medicines used to treat patients with ADHD, especially when these patients also have a history of nonmedical substance use. In addition, we suggest that today there is an opportunity to add a new and perhaps more hopeful paradigm: the wider use of drug delivery systems that make products less attractive to drug abusers. This new drug abuse prevention paradigm holds great promise for efforts to reduce the nonmedical use of prescription controlled substances, including the prescription stimulants used to treat ADHD. To achieve the full potential of this new paradigm to reduce prescription drug abuse, it will be necessary to develop standards to assess the relative abuse resistance of various drug formulations and delivery systems, as well as meaningful incentives to foster the development of these abuse-resistant delivery systems for controlled substances.

  8. Differential neural representation of oral ethanol by central taste-sensitive neurons in ethanol-preferring and genetically heterogeneous rats

    PubMed Central

    Wilson, David M.; Brasser, Susan M.

    2011-01-01

    In randomly bred rats, orally applied ethanol stimulates neural substrates for appetitive sweet taste. To study associations between ethanol's oral sensory characteristics and genetically mediated ethanol preference, we made electrophysiological recordings of oral responses (spike density) by taste-sensitive nucleus tractus solitarii neurons in anesthetized selectively bred ethanol-preferring (P) rats and their genetically heterogeneous Wistar (W) control strain. Stimuli (25 total) included ethanol [3%, 5%, 10%, 15%, 25%, and 40% (vol/vol)], a sucrose series (0.01, 0.03, 0.1, 0.3, 0.5, and 1 M), and other sweet, salt, acidic, and bitter stimuli; 50 P and 39 W neurons were sampled. k-means clustering applied to the sucrose response series identified cells showing high (S1) or relatively low (S0) sensitivity to sucrose. A three-way factorial analysis revealed that activity to ethanol was influenced by a neuron's sensitivity to sucrose, ethanol concentration, and rat line (P = 0.01). Ethanol produced concentration-dependent responses in S1 neurons that were larger than those in S0 cells. Although responses to ethanol by S1 cells did not differ between lines, neuronal firing rates to ethanol in S0 cells increased across concentration only in P rats. Correlation and multivariate analyses revealed that ethanol evoked responses in W neurons that were strongly and selectively associated with activity to sweet stimuli, whereas responses to ethanol by P neurons were not easily associated with activity to representative sweet, sodium salt, acidic, or bitter stimuli. These findings show differential central neural representation of oral ethanol between genetically heterogeneous rats and P rats genetically selected to prefer alcohol. PMID:21918002

  9. Differential neural representation of oral ethanol by central taste-sensitive neurons in ethanol-preferring and genetically heterogeneous rats.

    PubMed

    Lemon, Christian H; Wilson, David M; Brasser, Susan M

    2011-12-01

    In randomly bred rats, orally applied ethanol stimulates neural substrates for appetitive sweet taste. To study associations between ethanol's oral sensory characteristics and genetically mediated ethanol preference, we made electrophysiological recordings of oral responses (spike density) by taste-sensitive nucleus tractus solitarii neurons in anesthetized selectively bred ethanol-preferring (P) rats and their genetically heterogeneous Wistar (W) control strain. Stimuli (25 total) included ethanol [3%, 5%, 10%, 15%, 25%, and 40% (vol/vol)], a sucrose series (0.01, 0.03, 0.1, 0.3, 0.5, and 1 M), and other sweet, salt, acidic, and bitter stimuli; 50 P and 39 W neurons were sampled. k-means clustering applied to the sucrose response series identified cells showing high (S(1)) or relatively low (S(0)) sensitivity to sucrose. A three-way factorial analysis revealed that activity to ethanol was influenced by a neuron's sensitivity to sucrose, ethanol concentration, and rat line (P = 0.01). Ethanol produced concentration-dependent responses in S(1) neurons that were larger than those in S(0) cells. Although responses to ethanol by S(1) cells did not differ between lines, neuronal firing rates to ethanol in S(0) cells increased across concentration only in P rats. Correlation and multivariate analyses revealed that ethanol evoked responses in W neurons that were strongly and selectively associated with activity to sweet stimuli, whereas responses to ethanol by P neurons were not easily associated with activity to representative sweet, sodium salt, acidic, or bitter stimuli. These findings show differential central neural representation of oral ethanol between genetically heterogeneous rats and P rats genetically selected to prefer alcohol.

  10. Differential Influences of Ethanol on Early Exposure to Racemic Methylphenidate Compared with Dexmethylphenidate in Humans

    PubMed Central

    Straughn, Arthur B.; Reeves, Owen T.; Bernstein, Hilary; Bell, Guinevere H.; Anderson, Erica R.; Malcolm, Robert J.

    2013-01-01

    Enantioselective hydrolysis of oral racemic methylphenidate (dl-MPH) by carboxylesterase 1 (CES1) limits the absolute bioavailability of the pharmacologically active d-MPH isomer to approximately 30% and that of the inactive l-MPH to only 1–2%. Coadministration of dl-MPH with ethanol results in elevated d-MPH plasma concentrations accompanied by CES1-mediated enantioselective transesterification of l-MPH to l-ethylphenidate (EPH). The present study tested the hypothesis that administration of the pure isomer dexmethylphenidate (d-MPH) will overcome the influence of ethanol on d-MPH absorption by eliminating competitive CES1-mediated presystemic metabolism of l-MPH to l-EPH. Twenty-four healthy volunteers received dl-MPH (0.3 mg/kg) or d-MPH (0.15 mg/kg), with or without ethanol (0.6 g/kg). During the absorption phase of dl-MPH, concomitant ethanol significantly elevated d-MPH plasma concentrations (44–99%; P < 0.005). Furthermore, immediately following the ethanol drink the subjective effects of “high,” “good,” “like,” “stimulated,” and overall “effect” were significantly potentiated (P ≤ 0.01). Plasma l-EPH concentrations exceeded those of l-MPH. Ethanol combined with pure d-MPH did not elevate plasma d-MPH concentrations during the absorption phase, and the ethanol-induced potentiation of subjective effects was delayed relative to dl-MPH-ethanol. These findings are consistent with l-MPH competitively inhibiting presystemic CES1 metabolism of d-MPH. Ethanol increased the d-MPH area under the curve (AUC)0-inf by 21% following dl-MPH (P < 0.001) and 14% for d-MPH (P = 0.001). In men receiving d-MPH-ethanol, the d-MPH absorption partial AUC0.5–2 hours was 2.1 times greater and the time to maximum concentration (Tmax) occurred 1.1 hours earlier than in women, consistent with an increased rate of d-MPH absorption reducing hepatic extraction. More rapid absorption of d-MPH carries implications for increased abuse liability. PMID:23104969

  11. Circadian activity rhythms and voluntary ethanol intake in male and female ethanol-preferring rats: effects of long-term ethanol access.

    PubMed

    Rosenwasser, Alan M; McCulley, Walter D; Fecteau, Matthew

    2014-11-01

    Chronic alcohol (ethanol) intake alters fundamental properties of the circadian clock. While previous studies have reported significant alterations in free-running circadian period during chronic ethanol access, these effects are typically subtle and appear to require high levels of intake. In the present study we examined the effects of long-term voluntary ethanol intake on ethanol consumption and free-running circadian period in male and female, selectively bred ethanol-preferring P and HAD2 rats. In light of previous reports that intermittent access can result in escalated ethanol intake, an initial 2-week water-only baseline was followed by either continuous or intermittent ethanol access (i.e., alternating 15-day epochs of ethanol access and ethanol deprivation) in separate groups of rats. Thus, animals were exposed to either 135 days of continuous ethanol access or to five 15-day access periods alternating with four 15-day periods of ethanol deprivation. Animals were maintained individually in running-wheel cages under continuous darkness throughout the experiment to allow monitoring of free-running activity and drinking rhythms, and 10% (v/v) ethanol and plain water were available continuously via separate drinking tubes during ethanol access. While there were no initial sex differences in ethanol drinking, ethanol preference increased progressively in male P and HAD2 rats under both continuous and intermittent-access conditions, and eventually exceeded that seen in females. Free-running period shortened during the initial ethanol-access epoch in all groups, but the persistence of this effect showed complex dependence on sex, breeding line, and ethanol-access schedule. Finally, while females of both breeding lines displayed higher levels of locomotor activity than males, there was little evidence for modulation of activity level by ethanol access. These results are consistent with previous findings that chronic ethanol intake alters free-running circadian

  12. Circadian Activity Rhythms and Voluntary Ethanol Intake in Male and Female Ethanol-Preferring Rats: Effects of Long-Term Ethanol Access

    PubMed Central

    Rosenwasser, Alan M.; McCulley, Walter D.; Fecteau, Matthew

    2014-01-01

    Chronic alcohol (ethanol) intake alters fundamental properties of the circadian clock. While previous studies have reported significant alterations in free-running circadian period during chronic ethanol access, these effects are typically subtle and appear to require high levels of intake. In the present study we examined the effects of long-term voluntary ethanol intake on ethanol consumption and free-running circadian period in male and female, selectively bred ethanol-preferring P and HAD2 rats. In light of previous reports that intermittent access can result in escalated ethanol intake, an initial 2-week water-only baseline was followed by either continuous or intermittent ethanol access (i.e., alternating 15-day epochs of ethanol access and ethanol deprivation) in separate groups of rats. Thus, animals were exposed to either 135 days of continuous ethanol access or to five 15-day access periods alternating with four 15-day periods of ethanol deprivation. Animals were maintained individually in running-wheel cages under continuous darkness throughout the experiment to allow monitoring of free-running activity and drinking rhythms, and 10% (v/v) ethanol and plain water were available continuously via separate drinking tubes during ethanol access. While there were no initial sex differences in ethanol drinking, ethanol preference increased progressively in male P and HAD2 rats under both continuous and intermittent-access conditions, and eventually exceeded that seen in females. Free-running period shortened during the initial ethanol-access epoch in all groups, but the persistence of this effect showed complex dependence on sex, breeding line, and ethanol-access schedule. Finally, while females of both breeding lines displayed higher levels of locomotor activity than males, there was little evidence for modulation of activity level by ethanol access. These results are consistent with previous findings that chronic ethanol intake alters free-running circadian

  13. Positive relationship between dietary fat, ethanol intake, triglycerides, and hypothalamic peptides: counteraction by lipid-lowering drugs.

    PubMed

    Barson, Jessica R; Karatayev, Olga; Chang, Guo-Qing; Johnson, Deanne F; Bocarsly, Miriam E; Hoebel, Bartley G; Leibowitz, Sarah F

    2009-09-01

    Studies in both humans and animals suggest a positive relationship between the intake of ethanol and intake of fat, which may contribute to alcohol abuse. This relationship may be mediated, in part, by hypothalamic orexigenic peptides such as orexin (OX), which stimulate both consumption of ethanol and fat, and circulating triglycerides (TGs), which stimulate these peptides and promote consummatory behavior. The present study investigated this vicious cycle between ethanol and fat, to further characterize its relation to TGs and to test the effects of lowering TG levels. In Experiment 1, the behavioral relationship between fat intake and ethanol was confirmed. Adult male Sprague-Dawley rats, chronically injected intraperitoneally with ethanol (1g/kg) and tested in terms of their preference for a high-fat diet (HFD) compared with low-fat diet (LFD), showed a significant increase in their fat preference, compared with rats injected with saline, in measures of 2h and 24h intake. Experiment 2 tested the relationship of circulating TGs in this positive association between ethanol and fat, in rats chronically consuming 9% ethanol versus water and given acute meal tests (25kcal) of a HFD versus LFD. Levels of TGs were elevated in response to both chronic drinking of ethanol versus water and acute eating of a high-fat versus low-fat meal. Most importantly, ethanol and a HFD showed an interaction effect, whereby their combination produced a considerably larger increase in TG levels (+172%) compared to ethanol with a LFD (+111%). In Experiment 3, a direct manipulation of TG levels was found to affect ethanol intake. After intragastric administration of gemfibrozil (50mg/kg) compared with vehicle, TG levels were lowered by 37%, and ethanol intake was significantly reduced. In Experiment 4, the TG-lowering drug gemfibrozil also caused a significant reduction in the expression of the orexigenic peptide, OX, in the perifornical lateral hypothalamus. These results support the

  14. Positive relationship between dietary fat, ethanol intake, triglycerides and hypothalamic peptides: Counteraction by lipid-lowering drugs

    PubMed Central

    Barson, Jessica R.; Karatayev, Olga; Chang, Guo-Qing; Johnson, Deanne F.; Bocarsly, Miriam E.; Hoebel, Bartley G.; Leibowitz, Sarah F.

    2009-01-01

    Studies in both humans and animals suggest a positive relationship between the intake of ethanol and intake of fat, which may contribute to alcohol abuse. This relationship may be mediated, in part, by hypothalamic orexigenic peptides such as orexin (OX), which stimulate both consumption of ethanol and fat, and circulating triglycerides (TG), which stimulate these peptides and promote consummatory behavior. The present study investigated this vicious cycle between ethanol and fat, to further characterize its relation to TG and to test the effects of lowering TG levels. In Experiment 1, the behavioral relationship between fat intake and ethanol was confirmed. Adult male Sprague-Dawley rats, chronically injected with ethanol (1 g/kg i.p.) and tested in terms of their preference for a high-fat compared to low-fat diet, showed a significant increase in their fat preference, compared to rats injected with saline, in measures of 2 h and 24 h intake. Experiment 2 tested the relationship of circulating TG in this positive association between ethanol and fat, in rats chronically consuming 9% ethanol vs. water and given acute meal tests (25 kcal) of a high-fat vs. low-fat diet. Levels of TG were elevated in response to both chronic drinking of ethanol vs. water and acute eating of a high-fat vs. low-fat meal. Most importantly, ethanol and a high-fat diet showed an interaction effect, whereby their combination produced a considerably larger increase in TG levels (+172%) compared to ethanol with a low-fat diet (+111%). In Experiment 3, a direct manipulation of TG levels was found to affect ethanol intake. After administration of gemfibrozil (50 mg/kg i.g.) compared to vehicle, TG levels were lowered by 37%, and ethanol intake was significantly reduced. In Experiment 4, the TG-lowering drug gemfibrozil also caused a significant reduction in the expression of the orexigenic peptide OX, in the perifornical lateral hypothalamus. These results support the existence of a vicious

  15. Medical Emergencies Related to Ethanol and Illicit Drugs at an Annual, Nocturnal, Indoor, Electronic Dance Music Event.

    PubMed

    Calle, Paul; Sundahl, Nora; Maudens, Kristof; Wille, Sarah Mr; Van Sassenbroeck, Diederik; De Graeve, Koen; Gogaert, Stefan; De Paepe, Peter; Devriese, Dieter; Arno, Geert; Blanckaert, Peter

    2018-02-01

    Introduction Medical problems are frequently encountered during electronic dance music (EDM) events. Problem There are uncertainties about the frequencies and severity of intoxications with different types of recreational drugs: ethanol, "classical" illicit party drugs, and new psychoactive substances (NPS). Statistical data on the medical problems encountered during two editions of an indoor electronic dance event with around 30,000 attendants were retrieved from the Belgian Red Cross (Mechelen, Belgium) database. Data on drug use were prospectively collected from the patient (or a bystander), the clinical presentation, and/or toxicological screening. In the on-site medical station, 487 patients were treated (265 in 2013 and 222 in 2014). The most frequent reasons were trauma (n=171), headache (n=36), gastro-intestinal problems (n=44), and intoxication (n=160). Sixty-nine patients were transferred to a hospital, including 53 with severe drug-related symptoms. Analysis of blood samples from 106 intoxicated patients detected ethanol in 91.5%, 3,4-methylenedioxymethamphetamine (MDMA) in 34.0%, cannabis in 30.2%, cocaine in 7.5%, amphetamine in 2.8%, and gamma-hydroxybutyric acid (GHB) in 0.9% of patients (alone or in combination). In only six of the MDMA-positive cases, MDMA was the sole substance found. In 2014, the neuroleptic drug clozapine was found in three cases and ketamine in one. Additional analyses for NPS were performed in 20 cases. Only in one agitated patient, the psychedelic phenethylamines 25B-NBOMe and 25C-NBOMe were found. At this particular event, recreational drug abuse necessitated on-site medical treatment in one out of 350 attendants and a hospital transfer in one out of 1,000. Ethanol remains the most frequently abused (legal) drug, yet classical illicit recreational drugs are also frequently (co-) ingested. The most worrying observation was high-risk poly-drug use, especially among MDMA users. Regarding NPS, the number of cases was low and the

  16. Persistent escalation of alcohol drinking in C57BL/6J mice with intermittent access to 20% ethanol

    PubMed Central

    Hwa, Lara S.; Chu, Adam; Levinson, Sally A.; Kayyali, Tala M.; DeBold, Joseph F.; Miczek, Klaus A.

    2011-01-01

    Background Intermittent access to drugs of abuse, as opposed to continuous access, is hypothesized to induce a kindling-type transition from moderate to escalated use, leading to dependence. Intermittent 24-hour cycles of ethanol access and deprivation can generate high levels of voluntary ethanol drinking in rats. Methods The current study uses C57BL/6J mice (B6) in an intermittent access to 20% ethanol protocol to escalate ethanol drinking levels. Adult male and female B6 mice were given intermittent access to 20% ethanol on alternating days of the week with water available ad libitum. Ethanol consumption during the initial 2 hours of access was compared to a short term, limited access “binge” drinking procedure, similar to drinking-in-the-dark (DID). B6 mice were also assessed for ethanol dependence with handling-induced convulsion (HIC), a reliable measure of withdrawal severity. Results After 3 weeks, male mice given intermittent access to ethanol achieved high stable levels of ethanol drinking in excess of 20 g/kg/24h, reaching above 100 mg/dl BEC, and showed a significantly higher ethanol preference than mice given continuous access to ethanol. Also, mice given intermittent access drank about twice as much as DID mice in the initial 2-hour access period. B6 mice that underwent the intermittent access protocol for longer periods of time displayed more severe signs of alcohol withdrawal. Additionally, female B6 mice were given intermittent access to ethanol and drank significantly more than males (ca. 30 g/kg/24h). Discussion The intermittent access method in B6 mice is advantageous because it induces escalated, voluntary, and preferential per os ethanol intake, behavior that may mimic a cardinal feature of human alcohol dependence, though the exact nature and site of ethanol acting in the brain and blood as a result of intermittent access has yet to be determined. PMID:21631540

  17. 28 CFR 115.286 - Sexual abuse incident reviews.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Sexual abuse incident reviews. 115.286... Sexual abuse incident reviews. (a) The facility shall conduct a sexual abuse incident review at the conclusion of every sexual abuse investigation, including where the allegation has not been substantiated...

  18. 28 CFR 115.286 - Sexual abuse incident reviews.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Sexual abuse incident reviews. 115.286... Sexual abuse incident reviews. (a) The facility shall conduct a sexual abuse incident review at the conclusion of every sexual abuse investigation, including where the allegation has not been substantiated...

  19. 28 CFR 115.286 - Sexual abuse incident reviews.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Sexual abuse incident reviews. 115.286... Sexual abuse incident reviews. (a) The facility shall conduct a sexual abuse incident review at the conclusion of every sexual abuse investigation, including where the allegation has not been substantiated...

  20. Child abuse and mental disorders in Canada

    PubMed Central

    Afifi, Tracie O.; MacMillan, Harriet L.; Boyle, Michael; Taillieu, Tamara; Cheung, Kristene; Sareen, Jitender

    2014-01-01

    Background: Nationally representative Canadian data on the prevalence of child abuse and its relation with mental disorders are lacking. We used contemporary, nationally representative data to examine the prevalence of 3 types of child abuse (physical abuse, sexual abuse and exposure to intimate partner violence) and their association with 14 mental conditions, including suicidal ideation and suicide attempts. Methods: We obtained data from the 2012 Canadian Community Health Survey: Mental Health, collected from the 10 provinces. Respondents aged 18 years and older were asked about child abuse and were selected for the study sample (n = 23 395). The survey had a multistage stratified cluster design (household response rate 79.8%). Results: The prevalence of any child abuse was 32% (individual types ranged from 8% to 26%). All types of child abuse were associated with all mental conditions, including suicidal ideation and suicide attempts, after adjustment for sociodemographic variables (adjusted odds ratios ranged from 1.4 to 7.9). We found a dose–response relation, with increasing number of abuse types experienced corresponding with greater odds of mental conditions. Associations between child abuse and attention deficit disorder, suicidal ideation and suicide attempts showed stronger effects for women than men. Interpretation: We found robust associations between child abuse and mental conditions. Health care providers, especially those assessing patients with mental health problems, need to be aware of the relation between specific types of child abuse and certain mental conditions. Success in preventing child abuse could lead to reductions in the prevalence of mental disorders, suicidal ideation and suicide attempts. PMID:24756625

  1. Pharmacokinetic and pharmacodynamic drug interactions with ethanol (alcohol).

    PubMed

    Chan, Lingtak-Neander; Anderson, Gail D

    2014-12-01

    Ethanol (alcohol) is one of the most widely used legal drugs in the world. Ethanol is metabolized by alcohol dehydrogenase (ADH) and the cytochrome P450 (CYP) 2E1 drug-metabolizing enzyme that is also responsible for the biotransformation of xenobiotics and fatty acids. Drugs that inhibit ADH or CYP2E1 are the most likely theoretical compounds that would lead to a clinically significant pharmacokinetic interaction with ethanol, which include only a limited number of drugs. Acute ethanol primarily alters the pharmacokinetics of other drugs by changing the rate and extent of absorption, with more limited effects on clearance. Both acute and chronic ethanol use can cause transient changes to many physiologic responses in different organ systems such as hypotension and impairment of motor and cognitive functions, resulting in both pharmacokinetic and pharmacodynamic interactions. Evaluating drug interactions with long-term use of ethanol is uniquely challenging. Specifically, it is difficult to distinguish between the effects of long-term ethanol use on liver pathology and chronic malnutrition. Ethanol-induced liver disease results in decreased activity of hepatic metabolic enzymes and changes in protein binding. Clinical studies that include patients with chronic alcohol use may be evaluating the effects of mild cirrhosis on liver metabolism, and not just ethanol itself. The definition of chronic alcohol use is very inconsistent, which greatly affects the quality of the data and clinical application of the results. Our study of the literature has shown that a significantly higher volume of clinical studies have focused on the pharmacokinetic interactions of ethanol and other drugs. The data on pharmacodynamic interactions are more limited and future research addressing pharmacodynamic interactions with ethanol, especially regarding the non-central nervous system effects, is much needed.

  2. [Fuel ethanol production from cassava feedstock].

    PubMed

    Huang, Ribo; Chen, Dong; Wang, Qingyan; Shen, Naikun; Wei, Yutuo; Du, Liqin

    2010-07-01

    The regions suitable for growing cassava include five provinces in Southern China, with Guangxi alone accounting for over 65% of the total cassava production in the country. In this article, the state-of-the-art development of fuel ethanol production from cassava in China is illustrated by the construction of the cassava fuel ethanol plant with its annual production capacity of 200 000 metric tons. And in the meantime, problems and challenges encountered in the development of China's cassava fuel ethanol are highlighted and the strategies to address them are proposed.

  3. Mutation of the inhibitory ethanol site in GABAA ρ1 receptors promotes tolerance to ethanol-induced motor incoordination.

    PubMed

    Blednov, Yuri A; Borghese, Cecilia M; Ruiz, Carlos I; Cullins, Madeline A; Da Costa, Adriana; Osterndorff-Kahanek, Elizabeth A; Homanics, Gregg E; Harris, R Adron

    2017-09-01

    Genes encoding the ρ1/2 subunits of GABA A receptors have been associated with alcohol (ethanol) dependence in humans, and ρ1 was also shown to regulate some of the behavioral effects of ethanol in animal models. Ethanol inhibits GABA-mediated responses in wild-type (WT) ρ1, but not ρ1(T6'Y) mutant receptors expressed in Xenopus laevis oocytes, indicating the presence of an inhibitory site for ethanol in the second transmembrane helix. In this study, we found that ρ1(T6'Y) receptors expressed in oocytes display overall normal responses to GABA, the endogenous GABA modulator (zinc), and partial agonists (β-alanine and taurine). We generated ρ1 (T6'Y) knockin (KI) mice using CRISPR/Cas9 to test the behavioral importance of the inhibitory actions of ethanol on this receptor. Both ρ1 KI and knockout (KO) mice showed faster recovery from acute ethanol-induced motor incoordination compared to WT mice. Both KI and KO mutant strains also showed increased tolerance to motor impairment produced by ethanol. The KI mice did not differ from WT mice in other behavioral actions, including ethanol intake and preference, conditioned taste aversion to ethanol, and duration of ethanol-induced loss of righting reflex. WT and KI mice did not differ in levels of ρ1 or ρ2 mRNA in cerebellum or in ethanol clearance. Our findings indicate that the inhibitory site for ethanol in GABA A ρ1 receptors regulates acute functional tolerance to moderate ethanol intoxication. We note that low sensitivity to alcohol intoxication has been linked to risk for development of alcohol dependence in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Theories and measures of elder abuse.

    PubMed

    Abolfathi Momtaz, Yadollah; Hamid, Tengku Aizan; Ibrahim, Rahimah

    2013-09-01

    Elder abuse is a pervasive phenomenon around the world with devastating effects on the victims. Although it is not a new phenomenon, interest in examining elder abuse is relatively new. This paper aims to provide an overview of the aetiological theories and measures of elder abuse. The paper briefly reviews theories to explain causes of elder abuse and then discusses the most commonly used measures of elder abuse. Based on the reviewed theories, it can be concluded that elder abuse is a multifactorial problem that may affect elderly people from different backgrounds and involve a wide variety of potential perpetrators, including caregivers, adult children, and partners. The review of existing measurement instruments notes that many different screening and assessment instruments have been developed to identify elders who are at risk for or are victims of abuse. However, there is a real need for more measurements of elder abuse, as the current instruments are limited in scope. © 2013 The Authors. Psychogeriatrics © 2013 Japanese Psychogeriatric Society.

  5. Prescription Drug Abuse: From Epidemiology to Public Policy

    PubMed Central

    McHugh, R. Kathryn; Nielsen, Suzanne; Weiss, Roger D.

    2014-01-01

    Prescription drug abuse has reached an epidemic level in the United States. The prevalence of prescription drug abuse escalated rapidly beginning in the late 1990s, requiring a significant increase in research to better understand the nature and treatment of this problem. Since this time, a research literature has begun to develop and has provided important information about how prescription drug abuse is similar to, and different from the abuse of other substances. This introduction to a special issue of the Journal of Substance Abuse Treatment on prescription drug abuse provides an overview of the current status of the research literature in this area. The papers in this special issue include a sampling of the latest research on the epidemiology, clinical correlates, treatment, and public policy considerations of prescription drug abuse. Although much has been learned about prescription drug abuse in recent years, this research remains in early stages, particularly with respect to understanding effective treatments for this population. Future research priorities include studies on the interaction of prescription drugs with other licit and illicit substances, the impact of prescription drug abuse across the lifespan, the optimal treatment for prescription drug abuse and co-occurring conditions, and effective public policy initiatives for reducing prescription drug abuse. PMID:25239857

  6. Increased ethanol preference and serotonin 1A receptor-dependent attenuation of ethanol-induced hypothermia in PACAP-deficient mice.

    PubMed

    Tanaka, Kazuhiro; Kunishige-Yamamoto, Akiko; Hashimoto, Hitoshi; Shintani, Norihito; Hayata, Atsuko; Baba, Akemichi

    2010-01-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient mice display remarkable behavioral changes including increased novelty-seeking behavior and reduced hypothermia induced by either serotonin (5-HT)(1A) receptor agonists or ethanol. Because 5-HT(1A) receptors have been implicated in the development of alcohol dependence, we have examined ethanol preference in PACAP-deficient mice using a two-bottle choice and a conditioned place preference test, as well as additive effects of ethanol and 5-HT(1A) receptor agents on hypothermia. PACAP-deficient mice showed an increased preference towards ethanol compared with wild-type mice. However, they showed no preference for the ethanol compartment after conditioning and neither preference nor aversion to sucrose or quinine. The 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) restored the attenuated hypothermic response to ethanol in the mutants to similar levels in wild-type mice, with no effect in wild-types. In contrast, the 5-HT(1A) receptor antagonist WAY-100635 attenuated the ethanol-induced hypothermia in wild-type mice, with no effect in the mutants. These results demonstrate increased ethanol preference in PACAP-deficient mice that may be mediated by 5-HT(1A) receptor-dependent attenuation of ethanol-induced central inhibition. Copyright 2009 Elsevier Inc. All rights reserved.

  7. The Enough Abuse Campaign: Building the Movement to Prevent Child Sexual Abuse in Massachusetts

    ERIC Educational Resources Information Center

    Schober, Daniel J.; Fawcett, Stephen B.; Bernier, Jetta

    2012-01-01

    This case study describes the Enough Abuse Campaign, a multidisciplinary, statewide effort to prevent child sexual abuse in Massachusetts. The study uses the Institute of Medicine's Framework for Collaborative Community Action on Health to provide a systematic description of the campaign's process of implementation, which includes: (a) developing…

  8. Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice.

    PubMed

    Bahi, Amine; Dreyer, Jean-Luc

    2014-01-01

    We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7 days of extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol. Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

  9. Microbial physiology-based model of ethanol metabolism in subsurface sediments

    NASA Astrophysics Data System (ADS)

    Jin, Qusheng; Roden, Eric E.

    2011-07-01

    A biogeochemical reaction model was developed based on microbial physiology to simulate ethanol metabolism and its influence on the chemistry of anoxic subsurface environments. The model accounts for potential microbial metabolisms that degrade ethanol, including those that oxidize ethanol directly or syntrophically by reducing different electron acceptors. Out of the potential metabolisms, those that are active in the environment can be inferred by fitting the model to experimental observations. This approach was applied to a batch sediment slurry experiment that examined ethanol metabolism in uranium-contaminated aquifer sediments from Area 2 at the U.S. Department of Energy Field Research Center in Oak Ridge, TN. According to the simulation results, complete ethanol oxidation by denitrification, incomplete ethanol oxidation by ferric iron reduction, ethanol fermentation to acetate and H 2, hydrogenotrophic sulfate reduction, and acetoclastic methanogenesis: all contributed significantly to the degradation of ethanol in the aquifer sediments. The assemblage of the active metabolisms provides a frame work to explore how ethanol amendment impacts the chemistry of the environment, including the occurrence and levels of uranium. The results can also be applied to explore how diverse microbial metabolisms impact the progress and efficacy of bioremediation strategies.

  10. Animal models for medications development targeting alcohol abuse using selectively bred rat lines: Neurobiological and pharmacological validity

    PubMed Central

    Bell, Richard L.; Sable, Helen J.K.; Colombo, Giancarlo; Hyytia, Petri; Rodd, Zachary A.; Lumeng, Lawrence

    2012-01-01

    The purpose of this review paper is to present evidence that rat animal models of alcoholism provide an ideal platform for developing and screening medications that target alcohol abuse and dependence. The focus is on the 5 oldest international rat lines that have been selectively bred for a high alcohol-consumption phenotype. The behavioral and neurochemical phenotypes of these rat lines are reviewed and placed in the context of the clinical literature. The paper presents behavioral models for assessing the efficacy of pharmaceuticals for the treatment of alcohol abuse and dependence in rodents, with particular emphasis on rats. Drugs that have been tested for their effectiveness in reducing alcohol/ethanol consumption and/or self-administration by these rat lines and their putative site of action are summarized. The paper also presents some current and future directions for developing pharmacological treatments targeting alcohol abuse and dependence. PMID:22841890

  11. Ethanol Reversal of Oxycodone Tolerance in Dorsal Root Ganglia Neurons.

    PubMed

    Jacob, Joanna C; Sakakibara, Kensuke; Mischel, Ryan A; Henderson, Graeme; Dewey, William L; Akbarali, Hamid I

    2018-05-01

    Oxycodone is a semisynthetic opioid compound that is widely prescribed, used, and abused today, and has a well-established role in shaping the current opioid epidemic. Previously, we have shown that tolerance develops to the antinociceptive and respiratory depressive effects of oxycodone in mice, and that a moderate dose of acute ethanol or a protein kinase C (PKC) inhibitor reversed that tolerance. To investigate further if tolerance was occurring through neuronal mechanisms, our aims for this study were to assess the effects of acute and prolonged oxycodone in isolated dorsal root ganglia (DRG) neurons and to determine if this tolerance was reversed by either ethanol or a PKC inhibitor. We found that an acute exposure to 3 μ M oxycodone reduced neuronal excitability, as measured by increased threshold potentials and reduced action potential amplitude, without eliciting measurable changes in resting membrane potential. Exposure to 10 μ M oxycodone for 18-24 hours prevented oxycodone's effect on neuronal excitability, indicative of tolerance development. The development of opioid tolerance was mitigated in DRG neurons from β -arrestin 2 knockout mice. Oxycodone tolerance was reversed in isolated DRG neurons by the acute application of either ethanol (20 mM) or the PKC inhibitor, bisindolylmaleimide XI hydrochloride (Bis XI), when a challenge of 3 µ M oxycodone significantly reduced neuronal excitability following prolonged exposure. Through these studies, we concluded that oxycodone acutely reduced neuronal excitability, tolerance developed to this effect, and reversal of that tolerance occurred at the level of a single neuron, suggesting that reversal of oxycodone tolerance by either ethanol or Bis XI involves cellular mechanisms. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Neurosteroid Influences on Sensitivity to Ethanol

    PubMed Central

    Helms, Christa M.; Rossi, David J.; Grant, Kathleen A.

    2011-01-01

    This review will highlight a variety of mechanisms by which neurosteroids affect sensitivity to ethanol, including physiological states associated with activity of the hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–gonadal (HPG) axes, and the effects of chronic exposure to ethanol, in addition to behavioral implications. To date, γ-aminobutyric acid (GABAA) receptor mechanisms are a major focus of the modulation of ethanol effects by neuroactive steroids. While NMDA receptor mechanisms are gaining prominence in the literature, these complex data would be best discussed separately. Accordingly, GABAA receptor mechanisms are emphasized in this review with brief mention of some NMDA receptor mechanisms to point out contrasting neuroactive steroid pharmacology. Overall, the data suggest that neurosteroids are virtually ubiquitous modulators of inhibitory neurotransmission. Neurosteroids appear to affect sensitivity to ethanol in specific brain regions and, consequently, specific behavioral tests, possibly related to the efficacy and potency of ethanol to potentiate the release of GABA and increase neurosteroid concentrations. Although direct interaction of ethanol and neuroactive steroids at common receptor binding sites has been suggested in some studies, this proposition is still controversial. It is currently difficult to assign a specific mechanism by which neuroactive steroids could modulate the effects of ethanol in particular behavioral tasks. PMID:22654852

  13. Excitation of lateral habenula neurons as a neural mechanism underlying ethanol-induced conditioned taste aversion.

    PubMed

    Tandon, Shashank; Keefe, Kristen A; Taha, Sharif A

    2017-02-15

    The lateral habenula (LHb) has been implicated in regulation of drug-seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5 g kg -1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced

  14. An Investigation of the Relationship Between Substance Abuse and Child Abuse and Neglect.

    ERIC Educational Resources Information Center

    Black, Rebecca; Mayer, Joseph

    Research on the role of alcoholism and opiate addiction in child abuse and neglect is reviewed, and a study of the adequacy of child care in families of 200 alcohol or opiate addicted parents is reported. Demographic data is included, and incidence and characteristics of physical and sexual abuse and neglect are reported. Sex of the addicted…

  15. Substance abuse disorders in nurses.

    PubMed

    Griffith, J

    1999-01-01

    Substance abuse is a serious concern in the profession of nursing. The American Nurses Association (1997) estimates that 10% to 20% of nurses have substance abuse problems, and that 6% to 8% of registered nurses are impaired due to their abuse of alcohol and other drugs. Chemical dependency is considered a disease that requires treatment. Early identification and treatment of the chemically dependent nurse is important for the safety of the public and for the well-being of the nurse and her profession. This article addresses substance abuse from a biopsychosocial perspective, and includes a description of an approach to treatment and suggestions for the role of nursing administration.

  16. [Poisonings due to Substance Abuse Reported to the Poisons Information Centre Erfurt from 2002 to 2011].

    PubMed

    Liebetrau, G; Prasa, D; Hentschel, H; Deters, M

    2014-10-01

    Because of their importance for clinical toxicology, developments of sub-stance abuse reported to the Poisons Information Centre (PIC) Erfurt were investigated and compared to other reasons of human exposures. A retrospective analysis of all human exposures (exposures of humans to substances in abuse, accidental and unknown circumstances, and suicide attempts) (n=125,130) from the beginning of 2002 to the end of 2011 was undertaken according to substance classes, reasons of exposures, symptom severity, age groups, and gender. Cases of substance abuse (3,760, 3.0% of all exposures) continuously increased from 252 (92 with one and 160 with multiple substances) in 2002 to 507 in 2011 (239 with one and 268 with multiple substances). In relation to all exposures, only the abuse of multiple substances rose significantly (p<0.001). In comparison to all substances of exposure, ethanol, amphetamine-type stimulants, benzodiazepines/analogues, and liquid ecstasy abuse significantly (p<0.005) increased while cannabis and Brugmansia/Datura species abuse significantly (p<0.05) decreased. Substance abuse significantly (p<0.001) more often caused moderate (23.7%) and severe symptoms (6.1%) than in suicide attempts (9.6%; 4.4%). First legal highs exposures were registered in 2010 and led significantly (p<0.001) more often to moderate symptoms (50%) than cannabis exposures (19.4%). The clinical significance of substance abuse is shown by the fact that it resulted more often in moderate and severe symptoms than suicide attempts. Data on substance abuse from PICs could supplement official annual drug reports in aspects of clinical toxicology. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Ethanol enhances carbachol-induced protease activation and accelerates Ca2+ waves in isolated rat pancreatic acini.

    PubMed

    Orabi, Abrahim I; Shah, Ahsan U; Muili, Kamaldeen; Luo, Yuhuan; Mahmood, Syeda Maham; Ahmad, Asim; Reed, Anamika; Husain, Sohail Z

    2011-04-22

    Alcohol abuse is a leading cause of pancreatitis, accounting for 30% of acute cases and 70-90% of chronic cases, yet the mechanisms leading to alcohol-associated pancreatic injury are unclear. An early and critical feature of pancreatitis is the aberrant signaling of Ca(2+) within the pancreatic acinar cell. An important conductor of this Ca(2+) is the basolaterally localized, intracellular Ca(2+) channel ryanodine receptor (RYR). In this study, we examined the effect of ethanol on mediating both pathologic intra-acinar protease activation, a precursor to pancreatitis, as well as RYR Ca(2+) signals. We hypothesized that ethanol sensitizes the acinar cell to protease activation by modulating RYR Ca(2+). Acinar cells were freshly isolated from rat, pretreated with ethanol, and stimulated with the muscarinic agonist carbachol (1 μM). Ethanol caused a doubling in the carbachol-induced activation of the proteases trypsin and chymotrypsin (p < 0.02). The RYR inhibitor dantrolene abrogated the enhancement of trypsin and chymotrypsin activity by ethanol (p < 0.005 for both proteases). Further, ethanol accelerated the speed of the apical to basolateral Ca(2+) wave from 9 to 18 μm/s (p < 0.0005; n = 18-22 cells/group); an increase in Ca(2+) wave speed was also observed with a change from physiologic concentrations of carbachol (1 μM) to a supraphysiologic concentration (1 mM) that leads to protease activation. Dantrolene abrogated the ethanol-induced acceleration of wave speed (p < 0.05; n = 10-16 cells/group). Our results suggest that the enhancement of pathologic protease activation by ethanol is dependent on the RYR and that a novel mechanism for this enhancement may involve RYR-mediated acceleration of Ca(2+) waves.

  18. Ethanol Enhances Carbachol-induced Protease Activation and Accelerates Ca2+ Waves in Isolated Rat Pancreatic Acini*

    PubMed Central

    Orabi, Abrahim I.; Shah, Ahsan U.; Muili, Kamaldeen; Luo, Yuhuan; Mahmood, Syeda Maham; Ahmad, Asim; Reed, Anamika; Husain, Sohail Z.

    2011-01-01

    Alcohol abuse is a leading cause of pancreatitis, accounting for 30% of acute cases and 70–90% of chronic cases, yet the mechanisms leading to alcohol-associated pancreatic injury are unclear. An early and critical feature of pancreatitis is the aberrant signaling of Ca2+ within the pancreatic acinar cell. An important conductor of this Ca2+ is the basolaterally localized, intracellular Ca2+ channel ryanodine receptor (RYR). In this study, we examined the effect of ethanol on mediating both pathologic intra-acinar protease activation, a precursor to pancreatitis, as well as RYR Ca2+ signals. We hypothesized that ethanol sensitizes the acinar cell to protease activation by modulating RYR Ca2+. Acinar cells were freshly isolated from rat, pretreated with ethanol, and stimulated with the muscarinic agonist carbachol (1 μm). Ethanol caused a doubling in the carbachol-induced activation of the proteases trypsin and chymotrypsin (p < 0.02). The RYR inhibitor dantrolene abrogated the enhancement of trypsin and chymotrypsin activity by ethanol (p < 0.005 for both proteases). Further, ethanol accelerated the speed of the apical to basolateral Ca2+ wave from 9 to 18 μm/s (p < 0.0005; n = 18–22 cells/group); an increase in Ca2+ wave speed was also observed with a change from physiologic concentrations of carbachol (1 μm) to a supraphysiologic concentration (1 mm) that leads to protease activation. Dantrolene abrogated the ethanol-induced acceleration of wave speed (p < 0.05; n = 10–16 cells/group). Our results suggest that the enhancement of pathologic protease activation by ethanol is dependent on the RYR and that a novel mechanism for this enhancement may involve RYR-mediated acceleration of Ca2+ waves. PMID:21372126

  19. Rosalie Wolf Memorial Lecture: Reconsidering assumptions regarding men as elder abuse perpetrators and as elder abuse victims.

    PubMed

    Kosberg, Jordan I

    2014-01-01

    From research findings and practice experiences, it is concluded that abuse of older men is especially invisible and underreported, compared to abuse of older women. It is proposed that attention should be directed not to gender, but to those conditions in different countries and cultures leading to abuse of both older men and women, including (but not limited to) economic problems, few alternatives to family care of the elderly, violence, changing characteristics of the family, ageism, and sexism. Advocates for the prevention of elder abuse should work together in combating, reducing, and eliminating the problem of elder abuse of both older men and older women.

  20. Differential Effects of TM4 Tryptophan Mutations on Inhibition of N-Methyl-D-Aspartate Receptors by Ethanol and Toluene

    PubMed Central

    Smothers, C. Thetford; Woodward, John J.

    2017-01-01

    The voluntary use and abuse of alcohol and inhalants is a recognized health problem throughout the world. Previous studies have shown that these agents affect brain function in a variety of ways including direct inhibition of key ion channels that regulate neuronal excitability. Among these, the N-methyl-D-aspartate (NMDA) receptor is particularly important given its key role in glutamatergic synaptic transmission, neuronal plasticity and learning and memory. Previous studies from this laboratory and others have identified key residues within transmembrane (TM) domains of the NMDA receptor that appear to regulate its sensitivity to alcohol and anesthetics. In this study, we extend these findings and examine the role of a TM4 residue in modulating sensitivity of recombinant NMDA receptors to ethanol and toluene. HEK293 cells were transfected with GluN1-1a and either wild-type or tryptophan-substituted GluN2(A–D) subunits and whole-cell currents were recorded using patch-clamp electrophysiology in the absence or presence of ethanol or toluene. Both ethanol (100 mM) and toluene (1 or 3 mM) reversibly inhibited glutamate-activated currents from wild-type NMDARs with GluN2B containing receptors showing heightened sensitivity to either agent. Substitution of tryptophan (W) at positions 825, 826, 823 or 850 in the TM4 domain of GluN2A, GluN2B, GluN2C or GluN2D subunits; respectively, significantly reduced the degree of inhibition by ethanol. In contrast, toluene inhibition of glutamate-activated currents in cells expressing the TM4-W mutants was not different from that of the wild-type controls. These data suggest that despite similarities in their action on NMDARs, ethanol and toluene may act at different sites to reduce ion flux through NMDA receptors. PMID:27814790

  1. Differential effects of TM4 tryptophan mutations on inhibition of N-methyl-d-aspartate receptors by ethanol and toluene.

    PubMed

    Smothers, C Thetford; Woodward, John J

    2016-11-01

    The voluntary use and abuse of alcohol and inhalants is a recognized health problem throughout the world. Previous studies have shown that these agents affect brain function in a variety of ways including direct inhibition of key ion channels that regulate neuronal excitability. Among these, the N-methyl-d-aspartate (NMDA) receptor is particularly important given its key role in glutamatergic synaptic transmission, neuronal plasticity and learning and memory. Previous studies from this laboratory and others have identified key residues within transmembrane (TM) domains of the NMDA receptor that appear to regulate its sensitivity to alcohol and anesthetics. In this study, we extend these findings and examine the role of a TM4 residue in modulating sensitivity of recombinant NMDA receptors to ethanol and toluene. HEK293 cells were transfected with GluN1-1a and either wild-type or tryptophan-substituted GluN2(A-D) subunits and whole-cell currents were recorded using patch-clamp electrophysiology in the absence or presence of ethanol or toluene. Both ethanol (100 mM) and toluene (1 or 3 mM) reversibly inhibited glutamate-activated currents from wild-type NMDARs with GluN2B containing receptors showing heightened sensitivity to either agent. Substitution of tryptophan (W) at positions 825, 826, 823 or 850 in the TM4 domain of GluN2A, GluN2B, GluN2C or GluN2D subunits; respectively, significantly reduced the degree of inhibition by ethanol. In contrast, toluene inhibition of glutamate-activated currents in cells expressing the TM4-W mutants was not different from that of the wild-type controls. These data suggest that despite similarities in their action on NMDARs, ethanol and toluene may act at different sites to reduce ion flux through NMDA receptors. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Evaluation of Bikers Against Child Abuse (BACA) program: A community intervention for child abuse victims.

    PubMed

    Ray, Dee C; Lilly, J P; Gallina, Nancy; MacIan, Paula; Wilson, Brittany

    2017-12-01

    Children who have experienced physical abuse benefit from a multitude of community interventions including support programs to address emotional and behavioral stability. This pilot study evaluated the services of Bikers Against Child Abuse (BACA), a community of bikers lending intervention to abused children, using a pre/post exploratory design. Participants (N=154) were children who had been referred by parents/guardians for current or past physical and/or sexual abuse. Parents/guardians of children were interviewed four times over a course of one year. Results indicated children demonstrated substantial improvements in their overall levels of emotional distress, conduct concerns, hyperactivity, and behavioral and emotional functioning. Overall, results support the premise that services provided by BACA may serve as a unique intervention for children who have experienced abuse. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. 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.

  4. Evaluating the abuse potential of opioids and abuse-deterrent -opioid formulations: A review of clinical study methodology.

    PubMed

    Setnik, Beatrice; Schoedel, Kerri A; Levy-Cooperman, Naama; Shram, Megan; Pixton, Glenn C; Roland, Carl L

    With the development of opioid abuse-deterrent formulations (ADFs), there is a need to conduct well-designed human abuse potential studies to evaluate the effectiveness of their deterrent properties. Although these types of studies have been conducted for many years, largely to evaluate inherent abuse potential of a molecule and inform drug scheduling, methodological approaches have varied across studies. The focus of this review is to describe current "best practices" and methodological adaptations required to assess abuse-deterrent opioid formulations for regulatory submissions. A literature search was conducted in PubMed® to review methodological approaches (study conduct and analysis) used in opioid human abuse potential studies. Search terms included a combination of "opioid," "opiate," "abuse potential," "abuse liability," "liking," AND "pharmacodynamic," and only studies that evaluated single doses of opioids in healthy, nondependent individuals with or without prior opioid experience were included. Seventy-one human abuse potential studies meeting the prespecified criteria were identified, of which 21 studies evaluated a purported opioid ADF. Based on these studies, key methodological considerations were reviewed and summarized according to participant demographics, study prequalification, comparator and dose selection, route of administration and drug manipulation, study blinding, outcome measures and training, safety, and statistical analyses. The authors recommend careful consideration of key elements (eg, a standardized definition of a "nondependent recreational user"), as applicable, and offer key principles and "best practices" when conducting human abuse potential studies for opioid ADFs. Careful selection of appropriate study conditions is dependent on the type of ADF technology being evaluated.

  5. Prior childhood sexual abuse in mothers of sexually abused children.

    PubMed

    Oates, R K; Tebbutt, J; Swanston, H; Lynch, D L; O'Toole, B I

    1998-11-01

    To see if mothers who were sexually abused in their own childhood are at increased risk of their children being sexually abused and to see if prior sexual abuse in mothers affects their parenting abilities. Sixty-seven mothers whose children had been sexually abused by others and 65 control mothers were asked about sexual abuse in their own childhood. The sexually abused children of mothers who had been sexually abused in their own childhood were compared with the sexually abused children of mothers who had not suffered child sexual abuse as children. Comparisons were made on self-esteem, depression and behavior in the children. Thirty-four percent of mothers of sexually abused children gave a history of sexual abuse in their own childhoods, compared with 12% of control mothers. Assessment of the sexually abused children for self-esteem, depression and behavior at the time of diagnosis, after 18 months and after 5 years showed no difference in any of these measures at any of the three time intervals between those whose mothers had suffered child sexual abuse and those whose mothers had not been abused. In this study, sexual abuse in a mother's own childhood was related to an increased risk of sexual abuse occurring in the next generation, although prior maternal sexual abuse did not effect outcome in children who were sexually abused.

  6. Process design considerations for optimal production of ethanol from lignocellulose using available yeasts, including natural pentose-fermenting yeasts, and their derivatives

    USDA-ARS?s Scientific Manuscript database

    To expand the biomass to fuel ethanol industry, process strategies are needed to foster the production and utilization of microorganisms which can survive and ferment both hexose (C6) and pentose (C5) sugars while exposed to inhibitors (such as ethanol, furfural, and hydroxymethylfurfural, or HMF). ...

  7. Ethanol production method and system

    DOEpatents

    Chen, M.J.; Rathke, J.W.

    1983-05-26

    Ethanol is selectively produced from the reaction of methanol with carbon monoxide and hydrogen in the presence of a transition metal carbonyl catalyst. Methanol serves as a solvent and may be accompanied by a less volatile co-solvent. The solution includes the transition metal carbonyl catalysts and a basic metal salt such as an alkali metal or alkaline earth metal formate, carbonate or bicarbonate. A gas containing a high carbon monoxide to hydrogen ratio, as is present in a typical gasifer product, is contacted with the solution for the preferential production of ethanol with minimal water as a byproduct. Fractionation of the reaction solution provides substantially pure ethanol product and allows return of the catalysts for reuse.

  8. The role of abuse-deterrent formulations in countering opioid misuse and abuse.

    PubMed

    Nguyen, V; Raffa, R B; Taylor, R; Pergolizzi, J V

    2015-12-01

    Pain is a prevalent, and due to the ageing population, increasing medical problem. Opioids are frequently prescribed to meet the unmet medical need. Unfortunately, with the increase in the legitimate use of opioids, there has been a corresponding increase in abuse. A practical way to retain the pain relief afforded by opioids while decreasing opportunities for abuse is to make it more difficult to extract the opioid from the product or to make it less desirable to do so by designing an abuse-deterrent formulation (ADF). We provide a brief overview of the strategies and early evidence related to opioid ADFs. Published and unpublished literature, websites, and other sources were searched for current opioid formulation options, including immediate-release and extended-release products. Each was summarized, reviewed and assessed. The strategies that have been used to design the current opioid ADFs involve one or more of four approaches: a physical barrier; incorporation of an opioid receptor antagonist (e.g. naloxone) that self-limits opioid action when taken in excess amount; inclusion of a noxious agent that is released during inappropriate use; or a pro-drug. Legitimate use of opioid analgesics carries with it certain risks, including the risk of abuse. The new ADFs utilize four major strategies and provide innovative additions to the armamentarium. They likely will become an important part of a comprehensive approach to limiting, although not eliminating, opioid misuse and abuse. © 2015 John Wiley & Sons Ltd.

  9. Preventing Internal Computer Abuse

    DTIC Science & Technology

    1986-12-01

    abusers of computer systems are individuals who are -’’internal" to and working for the victim organization (these include full-time employees , part...Moonlighting * Organizational Property * Nonuse/nondisclosure * Substance Abuse * Gambling Employee Assistance Program "Whistle Blower" Policy EDP Auditor 1...sensitive computer systems. Of all the controls discussed so far. the Employee Assistance Program ’ EAP

  10. Psychiatric disorders, spouse abuse and child abuse.

    PubMed

    Bland, R C; Orn, H

    1986-01-01

    The results of 2000 standardized psychiatric diagnostic interviews of randomly selected adult household residents of Edmonton showed that having had any psychiatric diagnosis increased the risk for being involved in spouse and child abuse, particularly for those with alcohol abuse/dependence plus anti-social personality or depression. Altogether 56% of spouse abusers and 69% of child abusers had a lifetime psychiatric diagnosis.

  11. Elder abuse.

    PubMed

    Kurrle, Susan

    2004-10-01

    Elder abuse is a common and yet often unrecognised problem in our community. With up to 5% of the community dwelling older population being victims of abuse, the general practitioner has a pivotal role in identifying this abuse. This article provides an outline of the definition of elder abuse, describes the types of abuse seen and the reasons for occurrence of abuse. It summarises the role of the GP in the identification and management of abuse and provides guidance on intervention strategies. Case studies are used to illustrate the issues discussed. Elder abuse is defined as any pattern of behaviour which causes physical, psychological, financial or social harm to an older person. The role of the GP in identifying abuse is critical. The vast majority of older people visit their GP at least once a year, and the GP often has a long standing relationship with their patient and the patient's family. They are therefore ideally placed to identify elder abuse.

  12. Ethanol Basics

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

    None

    2015-01-30

    Ethanol is a widely-used, domestically-produced renewable fuel made from corn and other plant materials. More than 96% of gasoline sold in the United States contains ethanol. Learn more about this alternative fuel in the Ethanol Basics Fact Sheet, produced by the U.S. Department of Energy's Clean Cities program.

  13. Cognitive and Emotional Differences between Abusive and Non-Abusive Fathers

    ERIC Educational Resources Information Center

    Francis, Karen J.; Wolfe, David A.

    2008-01-01

    Objective: Abusive fathers perpetrate a substantial portion of child physical abuse. Despite this, little is known about how they differ from non-abusive fathers. This study compared a broad range of cognitive and affective factors between physically abusive and non-abusive fathers. Methods: Abusive (n = 24) and non-abusive (n = 25) fathers…

  14. Modifications in adrenal hormones response to ethanol by prior ethanol dependence.

    PubMed

    Guaza, C; Borrell, S

    1985-03-01

    Ethanol was administered to rats by means of a liquid diet for 16 days; after an ethanol-free interval of four weeks, animals received a test (IP) dose of ethanol (2 g/kg), and the adrenocortical and adrenomedullary responses were evaluated. Chronically ethanol-exposed animals showed tolerance to the stimulatory effect of ethanol in the pituitary-adrenal axis. Likewise, previously dependent rats showed tolerance to the increase in the activity of the adrenomedullary function induced by acute administration of the drug. Our results indicate that chronic ethanol ingestion can induce persistent changes after complete alcohol abstinence.

  15. Instruments for Assessing Substance Abuse: A Review.

    ERIC Educational Resources Information Center

    Lambert, Matthew E.; Plescia, Joanne

    A review of the assessment literature on substance abuse has revealed 27 separate instruments for assessing substance abuse. These include 22 alcohol instruments and five instruments for assessing other drug abuse. The instruments are listed in a table that provides the title, source, description, population, and psychometric properties of each…

  16. Rescue of glutamate transport in the lateral habenula alleviates depression- and anxiety-like behaviors in ethanol-withdrawn rats.

    PubMed

    Kang, Seungwoo; Li, Jing; Bekker, Alex; Ye, Jiang-Hong

    2018-02-01

    Alcoholism and psychiatric disorders like depression and anxiety are often comorbid. Although the mechanisms underlying this comorbidity are unclear, emerging evidence suggests that maladaptation of the glial glutamate transporter GLT-1 may play a role. Findings from animal and human studies have linked aversive states, including those related to drugs of abuse and depression, to aberrant activity in the lateral habenula (LHb). The relationship between GLT-1 maladaptation, LHb activity, and abnormal behaviors related to alcohol withdrawal, however, remains unknown. Here we show that dihydrokainic acid (DHK), a GLT-1 blocker, potentiated glutamatergic transmission to LHb neurons in slices from ethanol naïve rats; this potentiation, though, was not observed in slices from rats withdrawn from repeated in vivo ethanol administration, suggesting reduced GLT-1 function. Furthermore, GLT-1 protein expression was reduced in the LHb of withdrawn rats. This reduction was restored by systemic administration of ceftriaxone, a β-lactam antibiotic known to increase GLT-1 expression. Systemic ceftriaxone treatment also normalized the hyperactivity of LHb neurons in slices from withdrawn rats, which was reversed by bath-applied DHK. Finally, systemic administration of ceftriaxone alleviated depression- and anxiety-like behaviors, which was fully blocked by intra-LHb administrations of DHK, suggesting that GLT-1's function in the LHb is critical. These findings highlight the significant role of LHb astrocytic GLT-1 in the hyperactivity of LHb neurons, and in depressive- and anxiety-like behaviors during ethanol withdrawal. Thus, GLT-1 in the LHb could serve as a therapeutic target for psychiatric disorders comorbid with ethanol withdrawal. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. 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.

  18. Typologies of Abuse among Afro-Trinidadian Women

    ERIC Educational Resources Information Center

    Hadeed, Linda F.; El-Bassel, Nabila

    2007-01-01

    This study examines typologies of abusive behaviors among Afro-Trinidadian women. A total of 17 women participated in a 2-hour, face-to-face interview. The findings suggest that women experience multiple types of abuse including physical, sexual, and emotional abuse and controlling behaviors. This article discusses the implications of the findings…

  19. Cue-induced reinstatement of ethanol seeking in Sardinian alcohol-preferring rats.

    PubMed

    Maccioni, Paola; Orrú, Alessandro; Korkosz, Agnieszka; Gessa, Gian Luigi; Carai, Mauro A M; Colombo, Giancarlo; Bienkowski, Przemyslaw

    2007-02-01

    The purpose of the present study was to characterize cue-induced reinstatement of ethanol seeking in selectively bred Sardinian alcohol-preferring (sP) rats trained to lever press for ethanol in 30-min self-administration sessions. Four responses on an "active" lever led to presentation of 0.1 ml of 15% (vol/vol) ethanol by a liquid dipper and concurrent activation of a set of discrete light and auditory cues. In a 70-min extinction/reinstatement session, responding was first extinguished for 60 min. Subsequently, different stimuli were delivered in a noncontingent manner and reinstatement of nonreinforced responding was assessed. Fifteen presentations of the ethanol-predictive stimulus complex, including the dipper cup containing 5 or 15% ethanol, potently reinstated responding on the previously active lever. The magnitude of reinstatement increased with the number of stimulus presentations and concentration of ethanol presented by the dipper cup. Fifteen presentations of the ethanol-predictive stimulus complex, including the dipper cup filled with water (0% ethanol), did not produce any reinstatement. These results indicate that (1) noncontingent presentations of the ethanol-predictive stimulus complex may reinstate ethanol seeking in sP rats and (2) the orosensory properties of ethanol may play an important role in reinstatement of ethanol seeking in sP rats. The latter finding concurs with clinical observations that odor and taste of alcoholic beverages elicit immediate craving responses in abstinent alcoholics.

  20. Inhibition of IKKβ Reduces Ethanol Consumption in C57BL/6J Mice.

    PubMed

    Truitt, Jay M; Blednov, Yuri A; Benavidez, Jillian M; Black, Mendy; Ponomareva, Olga; Law, Jade; Merriman, Morgan; Horani, Sami; Jameson, Kelly; Lasek, Amy W; Harris, R Adron; Mayfield, R Dayne

    2016-01-01

    Proinflammatory pathways in neuronal and non-neuronal cells are implicated in the acute and chronic effects of alcohol exposure in animal models and humans. The nuclear factor-κB (NF-κB) family of DNA transcription factors plays important roles in inflammatory diseases. The kinase IKKβ mediates the phosphorylation and subsequent proteasomal degradation of cytosolic protein inhibitors of NF-κB, leading to activation of NF-κB. The role of IKKβ as a potential regulator of excessive alcohol drinking had not previously been investigated. Based on previous findings that the overactivation of innate immune/inflammatory signaling promotes ethanol consumption, we hypothesized that inhibiting IKKβ would limit/decrease drinking by preventing the activation of NF-κB. We studied the systemic effects of two pharmacological inhibitors of IKKβ, TPCA-1 and sulfasalazine, on ethanol intake using continuous- and limited-access, two-bottle choice drinking tests in C57BL/6J mice. In both tests, TPCA-1 and sulfasalazine reduced ethanol intake and preference without changing total fluid intake or sweet taste preference. A virus expressing Cre recombinase was injected into the nucleus accumbens and central amygdala to selectively knock down IKKβ in mice genetically engineered with a conditional Ikkb deletion ( Ikkb F/F ). Although IKKβ was inhibited to some extent in astrocytes and microglia, neurons were a primary cellular target. Deletion of IKKβ in either brain region reduced ethanol intake and preference in the continuous access two-bottle choice test without altering the preference for sucrose. Pharmacological and genetic inhibition of IKKβ decreased voluntary ethanol consumption, providing initial support for IKKβ as a potential therapeutic target for alcohol abuse.

  1. Intrinsic Properties of Larval Zebrafish Neurons in Ethanol

    PubMed Central

    Ikeda, Hiromi; Delargy, Alison H.; Yokogawa, Tohei; Urban, Jason M.; Burgess, Harold A.; Ono, Fumihito

    2013-01-01

    The behavioral effects of ethanol have been studied in multiple animal models including zebrafish. Locomotion of zebrafish larvae is resistant to high concentrations of ethanol in bath solution. This resistance has been attributed to a lower systemic concentration of ethanol in zebrafish when compared with bath solution, although the mechanism to maintain such a steep gradient is unclear. Here we examined whether the intrinsic properties of neurons play roles in this resistance. In order to minimize the contribution of metabolism and diffusional barriers, larvae were hemisected and the anterior half immersed in a range of ethanol concentrations thereby ensuring the free access of bath ethanol to the brain. The response to vibrational stimuli of three types of reticulospinal neurons: Mauthner neurons, vestibulospinal neurons, and MiD3 neurons were examined using an intracellular calcium indicator. The intracellular [Ca2+] response in MiD3 neurons decreased in 100 mM ethanol, while Mauthner neurons and vestibulospinal neurons required >300 mM ethanol to elicit similar effects. The ethanol effect in Mauthner neurons was reversible following removal of ethanol. Interestingly, activities of MiD3 neurons displayed spontaneous recovery in 300 mM ethanol, suggestive of acute tolerance. Finally, we examined with mechanical vibration the startle response of free-swimming larvae in 300 mM ethanol. Ethanol treatment abolished long latency startle responses, suggesting a functional change in neural processing. These data support the hypothesis that individual neurons in larval zebrafish brains have distinct patterns of response to ethanol dictated by specific molecular targets. PMID:23658822

  2. Determining the Heritability of Ethanol-induced Locomotor Sensitization in Mice Using Short-term Behavioral Selection

    PubMed Central

    Linsenbardt, David N.; Boehm, Stephen L.

    2013-01-01

    Rationale Sensitization to the locomotor stimulant effects of alcohol (ethanol) is thought to be a heritable risk factor for the development of alcoholism that reflects progressive increases in the positive motivational effects of this substance. However, very little is known about the degree to which genes influence this complex behavioral phenomenon. Objectives The primary goal of this work was to determine the heritability of ethanol-induced locomotor sensitization in mice using short-term behavioral selection. Methods Genetically heterogeneous C57BL/6J (B6) × DBA/2J (D2) F2 mice were generated from B6D2F1 progenitors, phenotyped for the expression of locomotor sensitization, and bred for high (HLS) and low (LLS) expression of this behavior. Selective breeding was conducted in two independently generated replicate sets to increase the confidence of our heritability estimates and for future correlated trait analyses. Results Large and significant differences in locomotor sensitization between HLS and LLS lines were evident by the fourth generation. Twenty-two percent of the observed line difference(s) were attributable to genes (h2=.22). Interestingly, locomotor activity in the absence of ethanol was genetically correlated with ethanol sensitization; high activity was associated with high sensitization. Conclusions That changes in ethanol sensitivity following repeated exposures are genetically regulated highlights the relevance of studies aimed at determining how genes regulate susceptibility to ethanol-induced behavioral and neural adaptations. As alcohol use and abuse disorders develop following many repeated alcohol exposures, these data emphasize the need for future studies determining the genetic basis by which changes in response to alcohol occur. PMID:23732838

  3. Delta receptor antagonism, ethanol taste reactivity, and ethanol consumption in outbred male rats.

    PubMed

    Higley, Amanda E; Kiefer, Stephen W

    2006-11-01

    Naltrexone, a nonspecific opioid antagonist, produces significant changes in ethanol responsivity in rats by rendering the taste of ethanol aversive as well as producing a decrease in voluntary ethanol consumption. The present study investigated the effect of naltrindole, a specific antagonist of delta opioid receptors, on ethanol taste reactivity and ethanol consumption in outbred rats. In the first experiment, rats received acute treatment of naltrexone, naltrindole, or saline followed by the measurement of ethanol consumption in a short-term access period. The second experiment involved the same treatments and investigated ethanol palatability (using the taste-reactivity test) as well as ethanol consumption. Results indicated that treatment with 3 mg/kg naltrexone significantly affected palatability (rendered ethanol more aversive, Experiment 2) and decreased voluntary ethanol consumption (Experiments 1 and 2). The effects of naltrindole were inconsistent. In Experiment 1, 8 mg/kg naltrindole significantly decreased voluntary ethanol consumption but this was not replicated in Experiment 2. The 8 mg/kg dose produced a significant increase in aversive responding (Experiment 2) but did not affect ingestive responding. Lower doses of naltrindole (2 and 4 mg/kg) were ineffective in altering rats' taste-reactivity response to and consumption of ethanol. While these data suggest that delta receptors are involved in rats' taste-reactivity response to ethanol and rats' ethanol consumption, it is likely that multiple opioid receptors mediate both behavioral responses.

  4. Effects of S-Adenosylmethionine and Its Combinations With Taurine and/or Betaine on Glutathione Homeostasis in Ethanol-induced Acute Hepatotoxicity

    PubMed Central

    Lee, Seo Yeon; Ko, Kwang Suk

    2016-01-01

    Background Exposure to ethanol abuse and severe oxidative stress are risk factors for hepatocarcinoma. The aim of this study was to evaluate the effects of S-adenosylmethionine (SAMe) and its combinations with taurine and/or betaine on the level of glutathione (GSH), a powerful antioxidant in the liver, in acute hepatotoxicity induced by ethanol. Methods To examine the effects of SAMe and its combinations with taurine and/or betaine on ethanol-induced hepatotoxicity, AML12 cells and C57BL/6 mice were pretreated with SAMe, taurine, and/or betaine, followed by ethanol challenge. Cell viability was detected with an MTT assay. GSH concentration and mRNA levels of GSH synthetic enzymes were measured using GSH reductase and quantitative real-time reverse transcriptase-PCR. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with commercially available kits. Results Pretreatment of SAMe, with or without taurine and/or betaine, attenuated decreases in GSH levels and mRNA expression of the catalytic subunit of glutamate-cysteine ligase (GCL), the rate-limiting enzyme for GSH synthesis, in ethanol-treated cells and mice. mRNA levels of the modifier subunit of GCL and glutathione synthetase were increased in mice treated with SAMe combinations. SAMe, taurine, and/or betaine pretreatment restored serum ALT and AST levels to control levels in the ethanol-treated group. Conclusions Combinations of SAMe with taurine and/or betaine have a hepatoprotective effect against ethanol-induced liver injury by maintaining GSH homeostasis. PMID:27722142

  5. Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes.

    PubMed

    Rompala, Gregory R; Mounier, Anais; Wolfe, Cody M; Lin, Qishan; Lefterov, Iliya; Homanics, Gregg E

    2018-01-01

    While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2 , known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of

  6. Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes

    PubMed Central

    Rompala, Gregory R.; Mounier, Anais; Wolfe, Cody M.; Lin, Qishan; Lefterov, Iliya; Homanics, Gregg E.

    2018-01-01

    While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2, known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of

  7. Autoshaping of ethanol drinking in rats: effects of ethanol concentration and trial spacing.

    PubMed

    Tomie, Arthur; Wong, Karlvin; Apor, Khristine; Patterson-Buckendahl, Patricia; Pohorecky, Larissa A

    2003-11-01

    In two studies, we evaluated the effects of ethanol concentration and trial spacing on Pavlovian autoshaping of ethanol drinking in rats. In these studies, the brief insertion of an ethanol sipper conditioned stimulus (CS) was followed by the response-independent presentation of food unconditioned stimulus (US), inducing sipper CS-directed drinking conditioned responses (CRs) in all rats. In Experiment 1, the ethanol concentration in the sipper CS [0%-16% volume/volume (vol./vol.), in increments of 1%] was systematically increased within subjects across autoshaping sessions. Groups of rats received sipper CS-food US pairings (Paired/Ethanol), a CS-US random procedure (Random/Ethanol), or water sipper CS paired with food US (Paired/Water). In Experiment 2, saccharin-fading procedures were used to initiate, in the Ethanol group, drinking of 6% (vol./vol.) ethanol in 0.1% saccharin or, in the Water group, drinking of tap water in 0.1% saccharin. After elimination of saccharin, and across days, the duration of access to the sipper CS during each autoshaping trial was increased (5, 10, 12.5, 15, 17.5, and 20 s), and subsequently, across days, the duration of the mean intertrial interval (ITI) was increased (60, 90, 120, and 150 s). In Experiment 1, Paired/Ethanol and Random/Ethanol groups showed higher intake of ethanol, in terms of grams per kilogram of body weight, at higher ethanol concentrations, with more ethanol intake recorded in the Paired/Ethanol group. In Experiment 2, the Ethanol group drank more than was consumed by the Water group, and, for both groups, fluid intake increased with longer ITIs. Results support the suggestion that autoshaping contributes to sipper CS-directed ethanol drinking.

  8. N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations.

    PubMed

    Morais-Silva, Gessynger; Alves, Gabrielle Cunha; Marin, Marcelo T

    2016-11-01

    Ethanol addiction is a serious public health problem that still needs more effective pharmacological treatment. A key factor in the development and maintenance of this disease is the advent of neuroadaptations in the mesocorticolimbic brain pathway upon chronic ethanol abuse. In general, these neuroadaptations are maladaptive and affect numerous neurotransmitter systems and intracellular molecules. One of these molecules is ΔFosB, a transcription factor that is altered after chronic drug use. Behavioural sensitization is a useful model for the study of the neuroadaptations related to addiction. Recent works have shown a role for the imbalance of glutamatergic neurotransmission in the symptoms found in addicted people. In this sense, the treatment with N-acetylcysteine, a l-cysteine prodrug that acts by restoring extrasynaptic concentrations of glutamate through the activation of cystine-glutamate antiporter, has shown promising results in the treatment of addiction. Thus, an animal model of behavioural sensitization was used to evaluate the effects of N-acetylcysteine treatment in the behavioural and molecular alterations induced by chronic ethanol administration. Swiss mice were subject to 13 days of daily ethanol administration to induce behavioural sensitization. Two hours before each ethanol administration and locomotor activity evaluation, the animals received intraperitoneally N-acetylcysteine injections. Immediately after the last test session, their brains were removed for ΔFosB and cystine-glutamate antiporter quantification. It was found that N-acetylcysteine treatment blocked ethanol-induced behavioural sensitization, the increase of ΔFosB content in the prefrontal cortex, and its reduction in the nucleus accumbens. The results suggest a possible use of N-acetylcysteine in ethanol-related disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Increased ethane exhalation, an in vivo index of lipid peroxidation, in alcohol-abusers.

    PubMed Central

    Lettéron, P; Duchatelle, V; Berson, A; Fromenty, B; Fisch, C; Degott, C; Benhamou, J P; Pessayre, D

    1993-01-01

    Ethane exhalation was measured in 42 control subjects, 52 patients with various non-alcoholic liver diseases, and 89 alcohol abusers who had been admitted to hospital for alcohol withdrawal and assessment of liver disease (six with normal liver tests, 10 with steatosis with or without fibrosis, six with alcoholic hepatitis, 29 with cirrhosis, 34 with both cirrhosis and alcoholic hepatitis, and four with both cirrhosis and a hepatocellular carcinoma). Ethane exhalation was similar in control subjects and in patients with non-alcoholic liver diseases, but was five times higher in alcohol abusers. Ethane exhalation in alcohol abusers was significantly, but very weakly, correlated with the daily ethanol intake before hospital admission, and the histological score for steatosis, but not with the inflammation or alcoholic hepatitis scores. Ethane exhalation was inversely correlated with the duration of abstinence before the test. In nine alcoholic patients, the exhalation of ethane was measured repeatedly, and showed slow improvement during abstinence. Ethane exhalation was significantly but weakly correlated with the Pugh's score in patients with alcoholic cirrhosis. It is concluded that the mean ethane exhalation is increased in alcohol abusers. One of the possible mechanisms may be the presence of oxidizable fat in the liver. The weak correlation with the Pugh's score is consistent with the contribution of many other factors in the progression to severe liver disease. PMID:8472992

  10. Changes in oral ethanol self-administration patterns resulting from ethanol concentration manipulations.

    PubMed

    Slawecki, C J; Samson, H H

    1997-09-01

    A variety of initiation procedures have been used to develop oral ethanol consumption. Using the sucrose-substitution procedure, oral self-administration of ethanol-water solutions with ethanol concentrations as high as 40% can be initiated in food- and fluid-sated rats. An important question for these models is the relationship between ethanol concentration and self-administration patterns after initiation. This study examined the differential patterns of ethanol self-administration maintained by a range of ethanol solutions (10 to 30%) over a 5-week period, compared with rats maintained on 10% ethanol for 5 weeks. In 43 male Long Evans rats, the sucrose-substitution procedure was used to initiate responding maintained by 10% ethanol on a Fixed Ratio 4 schedule of reinforcement. The ethanol concentration presented was then increased to 30% in stepwise fashion and then returned to 10% [Ethanol Concentration Manipulation (ECM) group, n = 32], or 10% ethanol was maintained as the reinforcer for 5 weeks [Control (Con) group, n = 11]. Significant increases in ethanol intake and decreases in responding were associated with increased ethanol concentration. Although no overall differences in total session responding were observed in either group between week 1 and week 5 (10E vs. 10E), examination of changes in initial low responders of the ECM group revealed significant increases in responding that were not observed in the initial low responders of the Con group. Significant increases in momentary response rates were observed on both the ECM and Con groups, independent of the ethanol concentration presented. Increases in response rate in the ECM group were the result of increases in initial low rate and high rate responders; however, the increased response rates in the Con group were the result of increases only in the initial low rate responders. These data suggest that the ECM procedure can aid in the initiation of ethanol self-administration and may be particularly

  11. The intellectual profile of abused and neglected children in the Philippines: An analysis of SB5 IQ scores of sexually abused, physically abused and neglected children.

    PubMed

    Bengwasan, Peejay D

    2018-05-24

    Child abuse and neglect have been associated with cognitive deficits, among other effects on child development. This study explores the prediction that child abuse and neglect has an impact on Stanford-Binet Intelligence Scales 5th Edition (SB5) IQ scores, in relation to gender, age and type of abuse experienced. 300 children with experiences of abuse and neglect were included in the study, comprising 100 sexually abused, 100 physically abused and 100 neglected children. Overall, all scores on the SB5 were found to be significantly lower than the minimum average scores on the test. Verbal IQ (VIQ) scores were likewise found to be significantly lower than Nonverbal IQ (NVIQ) scores. Full Scale IQ (FSIQ) scores did not reveal heterogeneity when gender was factored in. Age and type of abuse (with a moderate effect size) on the other hand, showed significant differences among groups. Statistical analyses of SB5 Factor Index Scores revealed that abused children, in general, have significantly higher Visual-Spatial Processing (VS) and Quantitative Reasoning (QR) scores and lower scores in Knowledge (KN). There was a large effect size found in such an analysis. Age (with a large effect size), gender and type of abuse (with moderate effect sizes) give significant variations to this obtained profile. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Loss of Ethanol Conditioned Taste Aversion and Motor Stimulation in Knockin Mice with Ethanol-Insensitive α2-Containing GABAA Receptors

    PubMed Central

    Borghese, C. M.; McCracken, M. L.; Benavidez, J. M.; Geil, C. R.; Osterndorff-Kahanek, E.; Werner, D. F.; Iyer, S.; Swihart, A.; Harrison, N. L.; Homanics, G. E.; Harris, R. A.

    2011-01-01

    GABA type A receptors (GABAA-Rs) are potential targets of ethanol. However, there are multiple subtypes of this receptor, and, thus far, individual subunits have not been definitively linked with specific ethanol behavioral actions. Interestingly, though, a chromosomal cluster of four GABAA-R subunit genes, including α2 (Gabra2), was associated with human alcoholism (Am J Hum Genet 74:705–714, 2004; Pharmacol Biochem Behav 90:95–104, 2008; J Psychiatr Res 42:184–191, 2008). The goal of our study was to determine the role of receptors containing this subunit in alcohol action. We designed an α2 subunit with serine 270 to histidine and leucine 277 to alanine mutations that was insensitive to potentiation by ethanol yet retained normal GABA sensitivity in a recombinant expression system. Knockin mice containing this mutant subunit were tested in a range of ethanol behavioral tests. These mutant mice did not develop the typical conditioned taste aversion in response to ethanol and showed complete loss of the motor stimulant effects of ethanol. Conversely, they also demonstrated changes in ethanol intake and preference in multiple tests. The knockin mice showed increased ethanol-induced hypnosis but no difference in anxiolytic effects or recovery from acute ethanol-induced motor incoordination. Overall, these studies demonstrate that the effects of ethanol at GABAergic synapses containing the α2 subunit are important for specific behavioral effects of ethanol that may be relevant to the genetic linkage of this subunit with human alcoholism. PMID:20876231

  13. Fuel ethanol

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

    Not Available

    This report discusses the Omnibus Trade and Competitiveness Act of 1988 which requires GAO to examine fuel ethanol imports from Central America and the Caribbean and their impact on the U.S. fuel ethanol industry. Ethanol is the alcohol in beverages, such as beer, wine, and whiskey. It can also be used as a fuel by blending with gasoline. It can be made from renewable resources, such as corn, wheat, grapes, and sugarcane, through a process of fermentation. This report finds that, given current sugar and gasoline prices, it is not economically feasible for Caribbean ethanol producers to meet the currentmore » local feedstock requirement.« less

  14. [Child sexual abuse: an irremediable hurt?].

    PubMed

    Di Giacomo, Ester; Alamia, Alberto; Cicolari, Federica; Cimolai, Valentina; Clerici, Massimo

    2013-01-01

    The aim of this review was to provide the state of art of child sexual abuse and its psychophysical consequences. We assessed the evidence-based literature derived from PubMed, Embase, Medline, PsychINFO databases, including a thorough analysis of what has been published in the last 5 years, not neglecting previous publications essential to the argument for their scientific validity (methodological accuracy, recruited survey). Child sexual abuse is ubiquitous both regarding victims' gender and socio-economic conditions. The important consequences linked to what they suffered--either immediately or with adolescent or adult onset--are mediated by age and family support to trauma reprocessing as well as by the frequency of repetition of the abuse or familiarity with the abuser. These factors appear to be of primary importance--both at a physical and psychic level--and may be expressed in multiple manifestations, hence it is of utmost importance to pay timely attention to possible alarm signals revealing suspected abuse suffered by any underage person. Special emphasis is addressed towards some of the consequences for which child sexual abuse is considered to be a primary cause (e.g. post-traumatic stress disorder) and the perpetuation of such abuse, both short-term as well as long-term. Poor training, regarding this field, of various professionals (pediatricians, teachers, etc.) who each day work with minors, as well as the paucity of available treatment options point to an urgent need for prevention (including in-depth diagnosis/therapy) and early intervention.

  15. Child Abuse

    MedlinePlus

    ... puts a child at risk of harm. Child abuse can be physical, sexual or emotional. Neglect, or not providing for a child's needs, is also a form of abuse. Most abused children suffer greater emotional than physical damage. An abused child may become ...

  16. Effects of co-administration of ketamine and ethanol on the dopamine system via the cortex-striatum circuitry.

    PubMed

    Liu, Qing; Xu, Tian-Yong; Zhang, Zhi-Bi; Leung, Chi-Kwan; You, Ding-Yun; Wang, Shang-Wen; Yi, Shuai; Jing, Qiang; Xie, Run-Fang; Li, Huifang-Jie; Zeng, Xiao-Feng

    2017-06-15

    Ketamine and ethanol are increasingly being used together as recreational drugs in rave parties. Their effects on the dopamine (DA) system remain largely unknown. This study aimed to investigate the effects of consuming two different concentrations of ketamine with and without alcohol on the DA system. We employed the conditioned place preference (CPP) paradigm to evaluate the rewarding effects of the combined administration of two different doses of ketamine (30mg/kg and 60mg/kg) with ethanol (0.3156g/kg). We evaluated the effects of the combined drug treatment on the transcriptional output of tyrosine hydroxylase (TH), dopa decarboxylase (DDC), synaptosomal-associated protein 25 (SNAP25), and vesicular monoamine transporter 2 (VMAT2) as well as protein expression level of brain-derived neurotrophic factor (BDNF) in rat prefrontal cortex (PFC) and striatum. We found that rats exhibited a dose-dependent, drug-paired, place preference to ketamine and ethanol associated with an elevated DA level in the striatum but not in the PFC. Moreover, treatment involving low- or high-dose ketamine with or without ethanol caused a differential regulatory response in the mRNA levels of the four DA metabolism genes and the cellular protein abundance of BDNF via the cortex-striatum circuitry. This study investigated the molecular mechanisms that occur following the combined administration of ketamine and ethanol in the DA system, which could potentially lead to alterations in the mental status and behavior of ketamine/ethanol users. Our findings may aid the development of therapeutic strategies for substance abuse patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Prevalence of ethanol and illicit drugs in road traffic accidents in the centre of Portugal: An eighteen-year update.

    PubMed

    Costa, Nádia; Silva, Rosário; Mendonça, M Cristina; Real, Francisco Corte; Vieira, Duarte Nuno; Teixeira, Helena M

    2012-03-10

    This study presents the prevalence of ethanol and illicit drugs in fatal road traffic accident victims in the Centre of Portugal between January 1990 and December 2007. Among the violent deaths, road traffic accidents presented the highest percentage (around 35%; n=3095), but decreasing throughout the years. Accidents were preponderant in males (about 80%; n=2402), between 21 and 30 years-old. Accidents involving drivers (55%; n=1310) were of the most common, being the car the main vehicle (45%), followed by the motorcycle (40%). An alcohol analysis request was present in 50% of the cases (n=1687), but increasing each year. Ethanol concentrations >1.2g/L, the legal limit in Portugal, were found in 55% (n=283) of the cases. Concerning drugs of abuse requests, only 4.4% (n=137) and 17.3% (58 cases) of the cases included the analysis at the Forensic Pathology Department (FPD) and at the Medico-Legal Office (MLO), respectively. Among the road accident cases analysed, 18 were positive, mainly in men (84%), between 21 and 30 years-old; opiates (47.1%; n=8) and cannabinoids (50%; n=4) were the most found, at the FPD and at the MLO, respectively. In conclusion, ethanol was identified as a key factor to traffic accidents, which explains the definition of specific legislation and methods of enforcement to prohibit this form of impairing. Nevertheless, ethanol still remains the psychoactive substance most frequently identified in the blood of divers killed in road-traffic crashes, recommending additional actions of supervision and control. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. Substance abuse associated with elder abuse in the United States.

    PubMed

    Jogerst, Gerald J; Daly, Jeanette M; Galloway, Lara J; Zheng, Shimin; Xu, Yinghui

    2012-01-01

    Substance abuse by either victim or perpetrator has long been associated with violence and abuse. Sparse research is available regarding elder abuse and its association with substance abuse. The objective of this study was to evaluate the association of state-reported domestic elder abuse with regional levels of substance abuse. Census demographic and elder abuse data were sorted into substate regions to align with the substance use treatment-planning regions for 2269 US counties. From the 2269 US counties there were 229 substate regions in which there were 213,444 investigations of abuse. For the other Ns (reports and substantiations) there were fewer counties and regions. See first sentence of data analyses and first sentence of results. Elder abuse report rates ranged from .03 to .41% (80 regions), investigation rates .001 to .34% (229 regions), and substantiation rates 0 to .22% (184 regions). Elder abuse investigations and substantiations were associated with various forms of substance abuse. Higher investigation rates were significantly associated with a higher rate of any illicit drug use in the past month, a lower median household income, lower proportion of the population graduated high school, and higher population of Hispanics. Higher substantiation rates were significantly associated with higher rate of illicit drug use in the past month and higher population of Hispanics. It may be worthwhile for administrators of violence programs to pay particular attention to substance abuse among their clients and in their community's environment, especially if older persons are involved. Measures of documented elder abuse at the county level are minimal. To be able to associate substance abuse with elder abuse is a significant finding, realizing that the substance abuse can be by the victim or the perpetrator of elder abuse.

  19. Loss of ethanol conditioned taste aversion and motor stimulation in knockin mice with ethanol-insensitive α2-containing GABA(A) receptors.

    PubMed

    Blednov, Y A; Borghese, C M; McCracken, M L; Benavidez, J M; Geil, C R; Osterndorff-Kahanek, E; Werner, D F; Iyer, S; Swihart, A; Harrison, N L; Homanics, G E; Harris, R A

    2011-01-01

    GABA type A receptors (GABA(A)-Rs) are potential targets of ethanol. However, there are multiple subtypes of this receptor, and, thus far, individual subunits have not been definitively linked with specific ethanol behavioral actions. Interestingly, though, a chromosomal cluster of four GABA(A)-R subunit genes, including α2 (Gabra2), was associated with human alcoholism (Am J Hum Genet 74:705-714, 2004; Pharmacol Biochem Behav 90:95-104, 2008; J Psychiatr Res 42:184-191, 2008). The goal of our study was to determine the role of receptors containing this subunit in alcohol action. We designed an α2 subunit with serine 270 to histidine and leucine 277 to alanine mutations that was insensitive to potentiation by ethanol yet retained normal GABA sensitivity in a recombinant expression system. Knockin mice containing this mutant subunit were tested in a range of ethanol behavioral tests. These mutant mice did not develop the typical conditioned taste aversion in response to ethanol and showed complete loss of the motor stimulant effects of ethanol. Conversely, they also demonstrated changes in ethanol intake and preference in multiple tests. The knockin mice showed increased ethanol-induced hypnosis but no difference in anxiolytic effects or recovery from acute ethanol-induced motor incoordination. Overall, these studies demonstrate that the effects of ethanol at GABAergic synapses containing the α2 subunit are important for specific behavioral effects of ethanol that may be relevant to the genetic linkage of this subunit with human alcoholism.

  20. Screening for childhood physical and sexual abuse among outpatient substance abusers.

    PubMed

    Simpson, T L; Westerberg, V S; Little, L M; Trujillo, M

    1994-01-01

    Research demonstrates that substance-abusing individuals report substantially higher rates of childhood sexual and physical abuse than the general population. This study sought to test a method of identifying substance-abusing clients with histories of childhood sexual and/or physical abuse and to explore the differences between those reporting childhood abuse and those not. Files of substance abusing clients from two distinct time periods were examined for reports of childhood abuse. At Time 1 (n = 399) clients were not systematically asked about experiences of childhood abuse, and at Time 2 (n = 305) clients were routinely asked about this issue. Results indicate that significantly more male and female clients disclosed childhood abuse at Time 2. Additionally, male clients reporting childhood abuse appeared more distressed than those not reporting abuse; female clients reporting childhood abuse did not appear more distressed than their counterparts.

  1. Antioxidants prevent ethanol-associated apoptosis in fetal rhombencephalic neurons.

    PubMed

    Antonio, Angeline M; Druse, Mary J

    2008-04-14

    It is well known that ethanol damages the developing nervous system by augmenting apoptosis. Previously, this laboratory reported that ethanol augments apoptosis in fetal rhombencephalic neurons, and that the increased apoptosis is associated with reduced activity of the phosphatidylinositol 3-kinase pathway and downstream expression of pro-survival genes. Other laboratories have shown that another mechanism by which ethanol induces apoptosis in developing neurons is through the generation of reactive oxygen species (ROS) and the associated oxidative stress. The present study used an in vitro model to investigate the potential neuroprotective effects of several antioxidants against ethanol-associated apoptosis in fetal rhombencephalic neurons. The investigated antioxidants included three phenolics: (-)-epigallocatechin-3-gallate (EGCG), a flavanoid polyphenol found in green tea; curcumin, found in tumeric; and resveratrol (3,5,4'-trihydroxystilbene), a component of red wine. Additional antioxidants, including melatonin, a naturally occurring indole, and alpha-lipoic acid, a naturally occurring dithiol, were also investigated. These studies demonstrated that a 24-hour treatment of fetal rhombencephalic neurons with 75 mM ethanol caused a 3-fold increase in the percentage of apoptotic neurons. However, co-treatment of these cultures with any of the five different antioxidants prevented ethanol-associated apoptosis. Antioxidant treatment did not alter the extent of apoptosis in control neurons, i.e., those cultured in the absence of ethanol. These studies showed that several classes of antioxidants can exert neuroprotection against ethanol-associated apoptosis in fetal rhombencephalic neurons.

  2. Exploring the Correlates to Depression in Elder Abuse Victims: Abusive Experience or Individual Characteristics?

    PubMed

    Santos, Ana João; Nunes, Baltazar; Kislaya, Irina; Gil, Ana Paula; Ribeiro, Oscar

    2017-09-01

    Depression and depressive symptoms have been studied both as risk factors and consequences of elder abuse, even though the most common cross-sectional design of the studies does not allow inferring cause or consequence relationships. This study estimates the proportion of older adults who screened positive for depressive symptoms among those self-reporting elder abuse and examines whether individual characteristics and/or abusive experience aspects are associated with self-reported depressive symptoms. Participants were 510 older adults self-reporting experiences of abuse in family setting enrolled in the cross-sectional victims' survey of the Aging and Violence Study. Depressive symptoms were assessed through the abbreviated version of the Geriatric Depression Scale (GDS-5). Poisson regression was used to determine the prevalence ratio (PR) of screening depressive symptoms according to individual and abusive experience covariates: sex, age group, cohabitation, perceived social support, chronic diseases, functional status, violence type, perpetrator, and number of conducts. Women (PR = 1.18, 95% confidence interval [CI] = [1.04, 1.35]) individuals perceiving low social support level (PR = 1.36, 95% CI = [1.16, 1.60]) and with long-term illness (PR = 1.17, 95% CI = [1.02, 1.33]) were found to be associated with increased risk for screening depressive symptoms. In regard to abusive experience, only the number of abusive conducts increased the PR (PR = 1.07, 95% CI = [1.05, 1.09]). Routine screening for elder abuse should include psychological well-being assessment. Interventions toward risk alleviation for both mental health problems and elder abuse should target women perceiving low social support level and with long-term illness.

  3. Running increases ethanol preference.

    PubMed

    Werme, Martin; Lindholm, Sara; Thorén, Peter; Franck, Johan; Brené, Stefan

    2002-07-18

    Wheel running performed by rats is reinforcing, rewarding and possibly addictive. In this study we analyzed if wheel running could affect ethanol preference. Lewis rats, known to be both addiction-prone and to develop an excessive wheel running behavior, were given access to ethanol in a two-bottle free-choice paradigm. The animals reached a high and stable ethanol intake after 5 weeks. In the next phase, rats were subjected to ethanol withdrawal for 1, 2 or 4 weeks with or without access to running wheels. Finally animals were again given access to ethanol in the same two-bottle free-choice paradigm, combined with access to running wheels. The rats that ran in running wheels during 1 or 2, but not 4, weeks of ethanol withdrawal increased both ethanol intake and preference as compared with the control group that did not have access to the wheels. Previous studies have demonstrated that low doses of morphine increases ethanol preference. Here we show that also running potentiates ethanol intake and preference. Thus, running which shares many of the reinforcing properties with addictive drugs appears to potentiate rats to an increased preference for ethanol. Our results describe a behavioral interaction where running increases ethanol consumption.

  4. Military Dependents: Services Provide Limited Confidentiality in Family Abuse Cases

    DTIC Science & Technology

    2000-04-01

    regarding family abuse. To respond to this mandate, we determined (1) the extent of reported spousal and child abuse within the military, (2) the degree...violence and as emotional and financial maltreatment, including any actions that harm or limit the spouse’s freedom of choice. Child abuse includes...military services has established a Family Advocacy Program to provide family counseling and to help ensure the safety of alleged spousal and child abuse victims.

  5. Secondary School Experiences of Male Recovering Substance Abusers

    ERIC Educational Resources Information Center

    Maher, Rebecca C.

    2012-01-01

    Problem: Adolescents who begin abusing substances, including alcohol, prescription drugs, and illegal drugs often fail in school suffering life-altering consequences (Cox, Zhang, Johnson, & Bender, 2007). While plentiful research exists on substance abuse, there is a dearth of research on the school experiences of recovering substance abusers.…

  6. Substance use by soldiers who abuse their spouses.

    PubMed

    Martin, Sandra L; Gibbs, Deborah A; Johnson, Ruby E; Sullivan, Kristen; Clinton-Sherrod, Monique; Walters, Jennifer L Hardison; Rentz, E Danielle

    2010-11-01

    Data on 7,424 soldier spouse abuse offenders were analyzed to determine the prevalence of substance use during abusive incidents, and to examine differences between substance-using and non-substance-using offenders. Results showed that 25% of all offenders used substances during abusive incidents, with males and non-Hispanic Whites being more likely to hav e used substances. Substance-using offenders were more likely to perpetrate physical spouse abuse and more severe spouse abuse. These findings underscore the importance of educating military personnel (including commanders) about links between substance use and domestic violence, and of coordinating preventive and therapeutic substance abuse and violence-related interventions.

  7. Definition and identification of child abuse by Finnish public health nurses.

    PubMed

    Paavilainen, Eija; Tarkka, Marja-Terttu

    2003-01-01

    The purpose of this study was to determine how public health nurses in Finland defined child abuse and how they assessed their capability to identify child abuse in the family. Public health nurses described child abuse as consisting of physical and emotional abuse. They described physical abuse as consisting of two categories, direct physical abuse towards children and other acts causing children physical harm. Emotional abuse included neglect, teasing the child, frightening the child, rejecting the child in the family, and forcing the child to assume an adult role. The nurses divided the identification of child abuse into two categories: tools for identifying child abuse and markers indicating child abuse. The tools for identifying abuse included knowledge acquisition and interactive skills, intuition, and the capacity of the nurse to handle problematic situations. Public health nurses identified child abuse in the child's behavior and appearance and in family behaviors. Public health nurses seem to be aware of child abuse, but further research is needed if they need more-specific skills regarding how to apply their theoretical knowledge to nursing practice to provide nursing care for abused children and their families.

  8. Overview: Clinical Identification of Sexually Abused Children.

    ERIC Educational Resources Information Center

    Corwin, David L.; Olafson, Erna

    1993-01-01

    This introduction to the special issue on clinical identification of sexually abused children reviews the history of the study of child sexual abuse and describes the 14 papers included in the special issue. (JDD)

  9. Executive Policy--Administration: E11.201, Illegal Drug and Substance Abuse. Executive Policy E11.203, Illegal Drugs and Alcohol Abuse.

    ERIC Educational Resources Information Center

    Hawaii Univ., Honolulu.

    This document includes two statements of policy for the University of Hawaii's drug and alcohol abuse prevention program. The first, "Illegal Drugs and Substance Abuse," opens with an introduction stating the University's general mission and that mission's incompatibility with substance abuse. A second section details the University's…

  10. Transdermal and oral dl-methylphenidate-ethanol interactions in C57BL/6J mice: transesterification to ethylphenidate and elevation of d-methylphenidate concentrations.

    PubMed

    Bell, Guinevere H; Novak, Andrew J; Griffin, William C; Patrick, Kennerly S

    2011-07-01

    We tested the hypothesis that C57BL/6J mice will model human metabolic interactions between dl-methylphenidate (MPH) and ethanol, placing an emphasis on the MPH transdermal system (MTS). Specifically, we asked: (1) will ethanol increase d-MPH biological concentrations, (2) will MTS facilitate the systemic bioavailability of l-MPH, and (3) will l-MPH enantioselectively interact with ethanol to yield l-ethylphenidate (l-EPH)? Mice were dosed with MTS (¼ of a 12.5 cm(2) patch on shaved skin) or a comparable oral dl-MPH dose (7.5 mg/kg), with or without ethanol (3.0 g/kg), and then placed in metabolic cages for 3 h. MPH and EPH isomer concentrations in blood, brain, and urine were analyzed by gas chromatographic-mass spectrometry monitoring of N-(S)-prolylpiperidyl fragments. As in humans, MTS greatly facilitated the absorption of l-MPH in this mouse strain. Similarly, ethanol led to the enantioselective formation of l-EPH and to an elevation in d-MPH concentrations with both MTS and oral MPH. Although only guarded comparisons between MTS and oral MPH can be made due to route-dependent drug absorption rate differences, MTS was associated with significant MPH-ethanol interactions. Ethanol-mediated increases in circulating concentrations of d-MPH carry toxicological and abuse liability implications should this animal model hold for ethanol-consuming attention-deficit hyperactivity disorder patients or coabusers. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

  11. Pavlovian conditioning with ethanol: sign-tracking (autoshaping), conditioned incentive, and ethanol self-administration.

    PubMed

    Krank, Marvin D

    2003-10-01

    Conditioned incentive theories of addictive behavior propose that cues signaling a drug's reinforcing effects activate a central motivational state. Incentive motivation enhances drug-taking and drug-seeking behavior. We investigated the behavioral response to cues associated with ethanol and their interaction with operant self-administration of ethanol. In two experiments, rats received operant training to press a lever for a sweetened ethanol solution. After operant training, the animals were given Pavlovian pairings of a brief and localized cue light with the sweetened ethanol solution (no lever present). Lever pressing for ethanol was then re-established, and the behavioral effects of the cue light were tested during an ethanol self-administration session. The conditioned responses resulting from pairing cue lights with the opportunity to ingest ethanol had three main effects: (1) induction of operant behavior reinforced by ethanol, (2) stimulation of ethanol-seeking behavior (magazine entries), and (3) signal-directed behavior (i.e., autoshaping, or sign-tracking). Signal-directed behavior interacted with the other two effects in a manner predicted by the location of the cue light. These conditioned responses interact with operant responding for ethanol reinforcement. These findings demonstrate the importance of Pavlovian conditioning effects on ethanol self-administration and are consistent with conditioned incentive theories of addictive behavior.

  12. Understanding Economic Abuse in the Lives of Survivors

    ERIC Educational Resources Information Center

    Postmus, Judy L.; Plummer, Sara-Beth; McMahon, Sarah; Murshid, N. Shaanta; Kim, Mi Sung

    2012-01-01

    Intimate partner violence (IPV) often includes economic abuse as one tactic commonly used by an abuser; unfortunately, there is a lack of empirical understanding of economic abuse. Additionally, research is limited on the predictors of economic self-sufficiency in the lives of women experiencing IPV. This paper furthers our knowledge about…

  13. Economic abuse in Lebanon: experiences and perceptions.

    PubMed

    Usta, Jinan; Makarem, Nisrine N; Habib, Rima R

    2013-03-01

    This article explores the experiences and perceptions of Lebanese women and men with economic abuse. Data were drawn from focus group discussions and face-to-face interviews with men, women and social workers. The findings reveal that Lebanese women experience many forms of economic abuse, including the withholding of earnings, restricted involvement in the labor force, and limited purchasing decisions. Inheritance laws and practices still favor men over women. Women tolerate economic abuse to avoid more serious forms of abuse and ensure family stability. Practical implications of the findings are presented.

  14. Ghrelin Increases GABAergic Transmission and Interacts with Ethanol Actions in the Rat Central Nucleus of the Amygdala

    PubMed Central

    Cruz, Maureen T; Herman, Melissa A; Cote, Dawn M; Ryabinin, Andrey E; Roberto, Marisa

    2013-01-01

    The neural circuitry that processes natural rewards converges with that engaged by addictive drugs. Because of this common neurocircuitry, drugs of abuse have been able to engage the hedonic mechanisms normally associated with the processing of natural rewards. Ghrelin is an orexigenic peptide that stimulates food intake by activating GHS-R1A receptors in the hypothalamus. However, ghrelin also activates GHS-R1A receptors on extrahypothalamic targets that mediate alcohol reward. The central nucleus of the amygdala (CeA) has a critical role in regulating ethanol consumption and the response to ethanol withdrawal. We previously demonstrated that rat CeA GABAergic transmission is enhanced by acute and chronic ethanol treatment. Here, we used quantitative RT-PCR (qRT-PCR) to detect Ghsr mRNA in the CeA and performed electrophysiological recordings to measure ghrelin effects on GABA transmission in this brain region. Furthermore, we examined whether acute or chronic ethanol treatment would alter these electrophysiological effects. Our qRT-PCR studies show the presence of Ghsr mRNA in the CeA. In naive animals, superfusion of ghrelin increased the amplitude of evoked inhibitory postsynaptic potentials (IPSPs) and the frequency of miniature inhibitory postsynaptic currents (mIPSCs). Coapplication of ethanol further increased the ghrelin-induced enhancement of IPSP amplitude, but to a lesser extent than ethanol alone. When applied alone, ethanol significantly increased IPSP amplitude, but this effect was attenuated by the application of ghrelin. In neurons from chronic ethanol-treated (CET) animals, the magnitude of ghrelin-induced increases in IPSP amplitude was not significantly different from that in naive animals, but the ethanol-induced increase in amplitude was abolished. Superfusion of the GHS-R1A antagonists 𝒟-Lys3-GHRP-6 and JMV 3002 decreased evoked IPSP and mIPSC frequency, revealing tonic ghrelin activity in the CeA. 𝒟-Lys3-GHRP-6 and JMV 3002

  15. Association of Drug Abuse and Child Abuse.

    ERIC Educational Resources Information Center

    Jaudes, Paula Kienberger; And Others

    1995-01-01

    Children born to mothers who used illicit drugs during pregnancy were assessed for subsequent abuse or neglect. Of the 513 children exposed inutero to drugs, 102 were substantiated as abused or neglected. Infants exposed inutero to drugs had a higher than expected risk of subsequent abuse compared to children in the general population. (Author/SW)

  16. Evaluation of a child sexual abuse prevention program.

    PubMed

    Chasan-Taber, L; Tabachnick, J

    1999-10-01

    A half-million children are believed to be sexually abused each year in the United States. In 1995, the American Medical Association declared sexual assault "a silent violent epidemic." The majority of efforts to stop child sexual abuse have focused on punishing abusers and treating victims and their families; prevention programs are uncommon and rely on educating children to report sexual abuse. This case study describes the evaluation of the first public health campaign designed to target adults for prevention. A baseline assessment of attitudes, awareness, knowledge, and policies was conducted in Vermont to identify facilitators and barriers to adult prevention of child sexual abuse. These included predisposing factors (50% of Vermont residents did not know the characteristics of an abuser), enabling factors (60% of Vermont residents did not know where to refer someone who may have sexual behavior problems), and reinforcing factors (when focus group participants knew an abuser, they were less likely to take action). This process guided the intervention, which included a broad-based media campaign targeting adults; a one-to-one communications strategy that provided information to agencies working with families at risk and a toll-free helpline for adults in an abuse situation; and a systems change strategy designed to educate decision-makers and leaders. Program evaluation measures included a random-digit dial survey, focus groups, a survey of Vermont decision-makers, and other data sets. The successes and limitations of these interventions, both as strategies in themselves and as data sources for evaluation, are discussed.

  17. The Genesis of Pedophilia: Testing the "Abuse-to-Abuser" Hypothesis.

    ERIC Educational Resources Information Center

    Fedoroff, J. Paul; Pinkus, Shari

    1996-01-01

    This study tested three versions of the "abuse-to-abuser" hypothesis by comparing men with personal histories of sexual abuse and men without sexual abuse histories. There was a statistically non-significant trend for assaulted offenders to be more likely as adults to commit genital assaults on children. Implications for the abuse-to-abuser…

  18. Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus

    PubMed Central

    Zhang, Dali; Xiong, Wei; Jackson, Michael F.

    2016-01-01

    Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5′-nucleotidase activity. Wild-type (CD73+/+) and ecto-5′-nucleotidase-deficient (CD73−/−) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73+/+ mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73+/+ mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg2+ conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5′-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73−/− mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5′-nucleotidase activity. PMID:27189965

  19. Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus.

    PubMed

    Zhang, Dali; Xiong, Wei; Jackson, Michael F; Parkinson, Fiona E

    2016-07-01

    Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5'-nucleotidase activity. Wild-type (CD73(+/+)) and ecto-5'-nucleotidase-deficient (CD73(-/-)) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73(+/+) mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73(+/+) mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg(2+) conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5'-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73(-/-) mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5'-nucleotidase activity. Copyright © 2016 The Author(s).

  20. Elder abuse in Chinese populations: a global review.

    PubMed

    Dong, XinQi

    2015-01-01

    This review focuses on the epidemiology of elder abuse in the global Chinese population with respect to its prevalence, risk factors, and consequences, as well as the perceptions of elder abuse. Evidence revealed that elder abuse and its subtypes are common among the global Chinese population with prevalence ranging from 0.2% to 64%. Younger age, lower income levels, depression, cognitive impairment, and lack of social support were consistently associated with self-reported elder abuse. Caregiver burden was a constant risk factor for the proclivity to elder abuse by caregivers. The adverse health outcomes of elder abuse included suicidal ideation and psychological stress. Some primary research gaps exist: such as, lack of consistency in measurements and recall periods, insufficient studies on the causal relationships between potential risk factors and elder abuse, consequences of elder abuse, and possible interventions. In order to reduce the risk of elder abuse in the global Chinese population, collaboration is encouraged among researchers, health care professionals, social service providers, and policy makers.

  1. Evaluation of French version of the Vulnerability to abuse screen scale (VASS), a elder abuse screening tool.

    PubMed

    Grenier, Florian; Capriz, Françoise; Lacroix-Hugues, Virginie; Paysant, François; Pradier, Christian; Franco, Alain

    2016-06-01

    The elder abuse is a major public health problem. In the world, almost 4 to 10% of people of more than 65 years would be abuse. The generalist practitioners report only 2% of the elder abuse. Furthermore, the evaluations of elder abuse screenings test found in the scientist literature were unsatisfactory. Evaluate the elder abuse screening capacities of the Vulnerability to abuse screen scale (VASS) in order to propose it to the doctors. VASS was translated in French. It's a quantitative and a forward-looking study whose the answers of people of more than 65 years old were analysed and compared in blind way to the answers of socials workers. 200 patients were included between March and May 2012 in the CHU of Cimiez, Nice. We found 104 patients in danger of abuse, 40 cases of abuse revealed by the socials workers, so 20% of abuses were reported by the gold standard. It means a sensibility of 90,9%, a specificity of 49,7% and a predictive value of 96,1% to a score of 1 to the test. The screening test VASS shown it useful to detect elder people in danger of abuse but a few discriminants and not adapted to patients who have cognitive pathologies. It's a screening tool usable by default, more sensitive than others tests in the scientist literature. However, these results ask the question of the useful of these tools of elder abuse screening in comparison with the education of doctors which made proofs of success in this subject.

  2. History of past sexual abuse in married observant Jewish women.

    PubMed

    Yehuda, Rachel; Friedman, Michelle; Rosenbaum, Talli Y; Labinsky, Ellen; Schmeidler, James

    2007-11-01

    The authors examined instances of past sexual abuse and related demographic characteristics in the self-reports of a select group of married observant Jewish women. Orthodox Jewish married women (N=380) ages 19 to 58 responded to advertisements asking them to complete an anonymous questionnaire about sexual experiences, including sexual abuse. Sexual abuse was reported by 26% of the respondents surveyed, with 16% reporting abuse occurring by the age of 13. More ultra-Orthodox Jews reported abuse than modern-Orthodox Jews. Women who were raised observant reported significantly less childhood sexual abuse than those who became observant later in life. Sexual abuse was associated with increased treatment-seeking for depression, marital counseling, or other emotional or psychological problems. While observant Jewish women live in a culture defined by a high degree of adherence to specific laws of conduct, including rules designed to regulate sexual contact, sexual abuse of various types still exists among them.

  3. Ethanol poisoning

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002644.htm Ethanol poisoning To use the sharing features on this page, please enable JavaScript. Ethanol poisoning is caused by drinking too much alcohol. ...

  4. The Cycle of Abuse: When Victims Become Offenders.

    PubMed

    Plummer, Malory; Cossins, Annie

    2016-07-19

    Various psychological theories exist in the literature to explain the behavior of men who commit child sex offences, including the belief that child sexual abuse (CSA) is a predisposing factor for the transition from victim to offender. These theories are, however, unable to explain the fact that while most victims of CSA are female, most perpetrators of CSA are male. The sex specificity of CSA in terms of victims and offenders suggests that the experience of CSA and its psychosocial effects may be different for boys, compared to girls. We hypothesize that CSA experiences may involve risk factors that affect the development of sexually abusive behavior for boys, rather than girls. Our aim was to determine whether the literature provides evidence of a cycle of abuse from victim to offender, and, if so, to document its characteristics. We undertook a comprehensive literature review of studies on both victims and offenders, including studies which revealed the following: age of onset of CSA, duration of abuse, gender of the abuser, the relationship between victim and abuser, grooming behaviors, the types and severity of abuse, and disclosure of abuse. While we found no evidence for the existence of a cycle of abuse for female CSA victims, we discovered evidence to support the existence of a cycle of abuse for male CSA victims who had experienced particular abuse characteristics. As an original contribution to the literature, we identified four factors that may be associated with a boy's transition from victim to offender as well as the methodological issues to be addressed in future research. Based on criminological theories, we argue that these four factors share a common theme, that is, that they represent experiences of power (for the abuser) and powerlessness (for the victim). © The Author(s) 2016.

  5. Clinical pharmacokinetics of non-opiate abused drugs.

    PubMed

    Busto, U; Bendayan, R; Sellers, E M

    1989-01-01

    The present review discusses the available data on the kinetic properties of non-opiate abused drugs including psychomotor stimulants, hallucinogens and CNS-depressants. Some of the drugs of abuse reviewed here are illicit drugs (e.g. cannabis, cocaine), while others are effective pharmacological agents but have the potential to be abused (e.g. benzodiazepines). Although some of the drugs mentioned in this review have been in use for centuries (e.g. caffeine, nicotine, cocaine, cannabis), knowledge of their kinetics and metabolism is very recent and in some cases still incomplete. This is partially due to the difficulties inherent in studying drugs of abuse in humans, and to the complex metabolism of some of these drugs (e.g. cannabis, caffeine) which has made it difficult to develop sensitive assays to determine biological pathways. Although drugs of abuse may have entirely different intrinsic pharmacological effects, the kinetic properties of such drugs are factors contributing to abuse and dependence. The pharmacokinetic properties that presumably contribute to self-administration and drug abuse include rapid delivery of the drug into the central nervous system and high free drug clearance. Kinetic characteristics also play an important role in the development of physical dependence and on the appearance of a withdrawal syndrome: the longer the half-life, the greater the likelihood of the development of physical dependence; the shorter the half-life, the earlier and more severe the withdrawal. The balance between these 2 factors, which has not yet been carefully studied, will also influence abuse patterns. The clinical significance of kinetic characteristics with respect to abuse is discussed where possible.

  6. Preclinical Evaluation of Riluzole: Assessments of Ethanol Self-Administration and Ethanol Withdrawal Symptoms

    PubMed Central

    Besheer, Joyce; Lepoutre, Veronique; Hodge, Clyde W.

    2010-01-01

    Background Many of the neurobehavioral effects of ethanol are mediated by inhibition of excitatory N-methyl-d-aspartate (NMDA) and enhancement of inhibitory γ-amino-butyric-acid (GABA) receptor systems. There is growing interest in drugs that alter these systems as potential medications for problems associated with alcoholism. The drug riluzole, approved for treatment of amyotrophic lateral sclerosis (ALS), inhibits NMDA and enhances GABAA receptor system activity. This study was designed to determine the preclinical efficacy of riluzole to modulate ethanol self-administration and withdrawal. Methods Male C57BL/6J mice were trained to lever press on a concurrent fixed-ratio 1 schedule of ethanol (10% v/v) versus water reinforcement during daily 16-hour sessions. Riluzole (1 to 40 mg/kg, IP) was evaluated on ethanol self-administration after acute and chronic (2 week) treatment. To determine if riluzole influences ethanol withdrawal-associated seizures, mice were fed an ethanol-containing or control liquid diet for 18 days. The effects of a single injection of riluzole (30 mg/kg) were examined on handling-induced convulsions after ethanol withdrawal. Results Acute riluzole (30 and 40 mg/kg) reduced ethanol self-administration during the first 4 hours of the session, which corresponds to the known pharmacokinetics of this drug. Ethanol self-administration was also reduced by riluzole after chronic treatment. Riluzole (30 mg/kg) significantly decreased the severity of ethanol-induced convulsions 2 hours after ethanol withdrawal. Conclusions These results demonstrate that riluzole decreases ethanol self-administration and may reduce ethanol withdrawal severity in mice. Thus, riluzole may have utility in the treatment of problems associated with alcoholism. PMID:19426166

  7. The ethanol pathway from Thermoanaerobacterium saccharolyticum improves ethanol production in Clostridium thermocellum

    DOE PAGES

    Hon, Shuen; Olson, Daniel G.; Holwerda, Evert K.; ...

    2017-06-27

    Clostridium thermocellum ferments cellulose, is a promising candidate for ethanol production from cellulosic biomass, and has been the focus of studies aimed at improving ethanol yield. Thermoanaerobacterium saccharolyticum ferments hemicellulose, but not cellulose, and has been engineered to produce ethanol at high yield and titer. Recent research has led to the identification of four genes in T. saccharolyticum involved in ethanol production: adhE, nfnA, nfnB and adhA. We introduced these genes into C. thermocellum and observed significant improvements to ethanol yield, titer, and productivity. The four genes alone, however, were insufficient to achieve in C. thermocellum the ethanol yields andmore » titers observed in engineered T. saccharolyticum strains, even when combined with gene deletions targeting hydrogen production. Here, this suggests that other parts of T. saccharolyticum metabolism may also be necessary to reproduce the high ethanol yield and titer phenotype in C. thermocellum.« less

  8. The ethanol pathway from Thermoanaerobacterium saccharolyticum improves ethanol production in Clostridium thermocellum

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

    Hon, Shuen; Olson, Daniel G.; Holwerda, Evert K.

    Clostridium thermocellum ferments cellulose, is a promising candidate for ethanol production from cellulosic biomass, and has been the focus of studies aimed at improving ethanol yield. Thermoanaerobacterium saccharolyticum ferments hemicellulose, but not cellulose, and has been engineered to produce ethanol at high yield and titer. Recent research has led to the identification of four genes in T. saccharolyticum involved in ethanol production: adhE, nfnA, nfnB and adhA. We introduced these genes into C. thermocellum and observed significant improvements to ethanol yield, titer, and productivity. The four genes alone, however, were insufficient to achieve in C. thermocellum the ethanol yields andmore » titers observed in engineered T. saccharolyticum strains, even when combined with gene deletions targeting hydrogen production. Here, this suggests that other parts of T. saccharolyticum metabolism may also be necessary to reproduce the high ethanol yield and titer phenotype in C. thermocellum.« less

  9. Chem I Supplement: Effects of Ethanol on Nutrition.

    ERIC Educational Resources Information Center

    Shorey, RoseAnn L.

    1979-01-01

    Malnutrition due to alcoholism is discussed. It includes energy from the metabolism of ethanol as it contributes to obesity, the replacement of nutritious foods by sources of ethanol, inhibition of vitamins being activated, the increase in excretion of valuable minerals, and toxicity to cells of organ systems. (Author/SA)

  10. Abuse Characteristics and Psychiatric Consequences Associated with Online Sexual Abuse.

    PubMed

    Say, Gökçe Nur; Babadağı, Zehra; Karabekiroğlu, Koray; Yüce, Murat; Akbaş, Seher

    2015-06-01

    The current study examined the rate and psychiatric correlates of sexual abuse involving the use of digital technologies by the offender in a wide sample of juvenile victims. Sociodemographic, abuse, and psychiatric characteristics of 662 sexually abused children and adolescents were evaluated. Of these, 93 reported that digital devices were used by the offender in several ways to facilitate the sexual abuse. The offender-victim relationship was initiated through the Internet in 39 victims. Involvement of digital technologies in sexual abuse was significantly associated with penetrative and recurrent form of sexual abuse commited by multiple offenders with coexisting violence. Additionally, victims of sexual abuse with a digital component were 4.21 times more likely to develop any psychopathology, 3.77 times more likely to have depression, and 2.14 times more likely to have post-traumatic stress disorder as a result of sexual abuse. These results indicated that the offender's use of digital technology may aid the initiation and facilitation of the sexual abuse of youths and may relate to more severe outcomes. This study revealed the importance of raising the awareness of professionals and the community about the potential risks associated with digital technologies and sexual abuse. Mental health professionals should consider this additional form of victimization, especially when dealing with sexual abuse victims.

  11. EFFECT OF ETHANOL ON NATURAL ATTENUATION OF BENZENE AT UST SITES

    EPA Science Inventory

    The use of ethanol as a fuel oxygenate has caused concern regarding the risk it poses as a groundwater contaminant. The natural bioattenuation of automobile fuels, including benzene, may be inhibited by the presence of ethanol as a result of a spill. Ethanol, in the presence of...

  12. Relative Fluid Novelty Differentially Alters the Time Course of Limited-Access Ethanol and Water Intake in Selectively Bred High Alcohol Preferring Mice

    PubMed Central

    Linsenbardt, David N.; Boehm, Stephen L.

    2015-01-01

    Background The influence of previous alcohol (ethanol) drinking experience on increasing the rate and amount of future ethanol consumption might be a genetically-regulated phenomenon critical to the development and maintenance of repeated excessive ethanol abuse. We have recently found evidence supporting this view, wherein inbred C57BL/6J (B6) mice develop progressive increases in the rate of binge-ethanol consumption over repeated Drinking-in-the-Dark (DID) ethanol access sessions (i.e. ‘front-loading’). The primary goal of the present study was to evaluate identical parameters in High Alcohol Preferring (HAP) mice to determine if similar temporal alterations in limited-access ethanol drinking develop in a population selected for high ethanol preference/intake under continuous (24hr) access conditions. Methods Using specialized volumetric drinking devices, HAP mice received 14 daily 2 hour DID ethanol or water access sessions. A subset of these mice was then given one day access to the opposite assigned fluid on day 15. Home cage locomotor activity was recorded concomitantly on each day of these studies. The possibility of behavioral/metabolic tolerance was evaluated on day 16 using experimenter administered ethanol. Results The amount of ethanol consumed within the first 15 minutes of access increased markedly over days. However, in contrast to previous observations in B6 mice, ethanol front-loading was also observed on day 15 in mice that only had previous DID experience with water. Furthermore, a decrease in the amount of water consumed within the first 15 minutes of access compared to animals given repeated water access was observed on day 15 in mice with 14 previous days of ethanol access. Conclusions These data further illustrate the complexity and importance of the temporal aspects of limited-access ethanol consumption, and suggest that previous procedural/fluid experience in HAP mice selectively alters the time course of ethanol and water consumption

  13. Postmortem ethanol in the setting of ethanol-containing automotive fuel.

    PubMed

    Garber, Mitchell A; Canfield, Dennis V; Lewis, Russell J; Simmons, Samuel D; Radisch, Deborah L

    2013-03-01

    The pilot of a light aircraft that crashed after a loss of power was found to have ethanol in the vitreous and the blood, but almost none in the urine. The globes of the eyes were intact, and the body was refrigerated after recovery until the autopsy was performed the following morning. The pilot was described as a "nondrinker," and additional specialized toxicology testing results were inconsistent with ethanol ingestion. The pilot's body was extensively exposed to fuel during the prolonged extraction. Investigation determined that the aircraft had been fueled with gasoline that contained 10% ethanol. Although exposure to automotive fuel has not been previously described as a source of ethanol in postmortem specimens, it may represent a source for the ethanol detected during postmortem toxicology testing in this case, and this finding may be relevant to other cases with similar exposure.

  14. Process for producing ethanol from plant biomass using the fungus Paecilomyces sp

    DOEpatents

    Wu, J.F.

    1985-08-08

    A process for producing ethanol from plant biomass is disclosed. The process includes forming a substrate from the biomass with the substrate including hydrolysates of cellulose and hemicellulose. A species of the fungus Paecilomyces which has the ability to ferment both cellobiose and xylose to ethanol is then selected and isolated. The substrate is inoculated with this fungus, and the inoculated substrate is then fermented under conditions favorable for cell viability and conversion of hydrolysates to ethanol. Finally, ethanol is recovered from the fermented substrate. 5 figs., 3 tabs.

  15. Influence of abuse on condom negotiation among Mexican-American women involved in abusive relationships.

    PubMed

    Davila, Yolanda R

    2002-01-01

    This study explored cultural and gender perspectives of abuse on condom negotiation behaviors for AIDS prevention among Mexican-American women in abusive intimate relationships. A convenience sample of 20 abused women participated in the study. Data were collected through a demographic questionnaire and audiotaped responses to a semistructured interview guide. Content analysis using QSR NUDIST was used to analyze the verbatim transcriptions of all participant interviews. The predominant category, "He always got his way," was developed in response to the content of the verbatim transcriptions. The category was further expanded to include the self-descriptive subcategories of "He beat me," "He made me feel bad," and "He forced me." Through content analysis, a relationship between abuse by male sexual partners and condom negotiation for AIDS prevention was identified. Trustworthiness of the data collection and analysis was established through methods suggested by Lincoln and Guba.

  16. Production of Ethanol From Newly Developed and Improved Winter Barley Cultivars.

    PubMed

    Nghiem, Nhuan P; Brooks, Wynse S; Griffey, Carl A; Toht, Matthew J

    2017-05-01

    Winter barley has attracted strong interest as a potential feedstock for fuel ethanol production in regions with mild winter climate such as the mid-Atlantic and northeastern USA. Ten recently developed and improved winter barley cultivars and breeding lines including five hulled and five hull-less lines were experimentally evaluated for potential ethanol production. The five hulled barley lines included three released cultivars (Thoroughbred, Atlantic, and Secretariat) and two breeding lines (VA09B-34 and VA11B-4). The five hull-less lines also included three released cultivars (Eve, Dan, and Amaze 10) and two breeding lines (VA08H-65 and VA13H-34). On the average, the hull-less barley cultivars produced more ethanol per unit mass because of their higher starch and β-glucan contents. However, since the hulled barley cultivars had higher agronomic yield, the potential ethanol production per acre of land for the two types were approximately equal. Among the ten cultivars tested, the hull-less cultivar Amaze 10 was the best one for ethanol production. The ethanol yield values obtained for this cultivar were 2.61 gal per bushel and 292 gal per acre.

  17. Assessment of transpulmonary absorption of ethanol from alcohol-based hand rub.

    PubMed

    Hautemanière, Alexis; Ahmed-Lecheheb, Djihane; Cunat, Lisiane; Hartemann, Philippe

    2013-03-01

    Alcohol-based hand rubs (ABHRs) have been associated with a reduction of nosocomial infections. Despite the worldwide introduction of these products in health care settings, the aim of this study was to assess the transpulmonary absorption of ethanol contains in ABHRs used by health care workers (HCWs) in real conditions of work shift. Twenty-six HCWs of Nancy University Hospital were included. Research consisted in monitoring participants during 4 hours of work shift to assess their exposure to ethanol. The measurement of ethanol vapors in exhaled breath was performed using a class B ethylometer (Alco-Sensor FST). Ethanol concentration in inhaled breath was measured using Gilian pump LFS-113. Concentration of ethanol, acetaldehyde, and acetate in blood and urine samples were determined using gas chromatography with flame ionization detector. Participants were 12% male and 88% female. The mean age was 40 ± 8 years. None of the employees included in the study presented any traces of ethanol or its metabolites in the blood or urine. Ethanol (0.08 ± 0.07 mg/L) was detected in the breath of 10 HCWs at 1 to 2 minutes postexposure. The mean concentration of ethanol in the inhaled air was 46.2 mg/m. Absorption of ethanol vapor from ABHRs among HCWs during their care activities was not detected. Quantification of ethanol fumes inhaled during 4 hours of work shift was below the regulatory limitations of exposure to ethanol. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  18. Routes of abuse of prescription opioid analgesics: a review and assessment of the potential impact of abuse-deterrent formulations.

    PubMed

    Gasior, Maciej; Bond, Mary; Malamut, Richard

    2016-01-01

    Prescription opioid analgesics are an important treatment option for patients with chronic pain; however, misuse, abuse and diversion of these medications are a major global public health concern. Prescription opioid analgesics can be abused via intended and non-intended routes of administration, both intact or after manipulation of the original formulation to alter the drug-delivery characteristics. Available data indicate that ingestion (with or without manipulation of the prescribed formulation) is the most prevalent route of abuse, followed by inhalation (snorting, smoking and vaping) and injection. However, reported routes of abuse vary considerably between different formulations. A number of factors have been identified that appear to be associated with non-oral routes of abuse, including a longer duration of abuse, younger age, male sex and a rural or socially deprived location. The development of abuse-deterrent formulations of prescription opioid analgesics is an important step toward reducing abuse of these medications. Available abuse-deterrent formulations aim to hinder extraction of the active ingredient, prevent administration through alternative routes and/or make abuse of the manipulated product less attractive, less rewarding or even aversive. There are currently five opioid analgesics with a Food and Drug Administration abuse-deterrent label, and a number of other products are under review. A growing body of evidence suggests that introduction of abuse-deterrent opioid analgesics in the USA has been associated with decreased rates of abuse of these formulations. The availability of abuse-deterrent formulations therefore appears to represent an important step toward curbing the epidemic of abuse of prescription opioid analgesics, while ensuring the availability of effective pain medications for patients with legitimate medical need.

  19. Prescription Drug Abuse

    MedlinePlus

    ... drug abuse. And it's illegal, just like taking street drugs. Why Do People Abuse Prescription Drugs? Some people abuse prescription drugs ... common risk of prescription drug abuse is addiction . People who abuse ... as if they were taking street drugs. That's one reason most doctors won't ...

  20. The ethanol pathway from Thermoanaerobacterium saccharolyticum improves ethanol production in Clostridium thermocellum.

    PubMed

    Hon, Shuen; Olson, Daniel G; Holwerda, Evert K; Lanahan, Anthony A; Murphy, Sean J L; Maloney, Marybeth I; Zheng, Tianyong; Papanek, Beth; Guss, Adam M; Lynd, Lee R

    2017-07-01

    Clostridium thermocellum ferments cellulose, is a promising candidate for ethanol production from cellulosic biomass, and has been the focus of studies aimed at improving ethanol yield. Thermoanaerobacterium saccharolyticum ferments hemicellulose, but not cellulose, and has been engineered to produce ethanol at high yield and titer. Recent research has led to the identification of four genes in T. saccharolyticum involved in ethanol production: adhE, nfnA, nfnB and adhA. We introduced these genes into C. thermocellum and observed significant improvements to ethanol yield, titer, and productivity. The four genes alone, however, were insufficient to achieve in C. thermocellum the ethanol yields and titers observed in engineered T. saccharolyticum strains, even when combined with gene deletions targeting hydrogen production. This suggests that other parts of T. saccharolyticum metabolism may also be necessary to reproduce the high ethanol yield and titer phenotype in C. thermocellum. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  1. The evaluation of the abuse liability of drugs.

    PubMed

    Johanson, C E

    1990-01-01

    In order to place appropriate restrictions upon the availability of certain therapeutic agents to limit their abuse, it is important to assess abuse liability, an important aspect of drug safety evaluation. However, the negative consequences of restriction must also be considered. Drugs most likely to be tested are psychoactive compounds with therapeutic indications similar to known drugs of abuse. Methods include assays of pharmacological profile, drug discrimination procedures, self-administration procedures, and measures of drug-induced toxicity including evaluations of tolerance and physical dependence. Furthermore, the evaluation of toxicity using behavioural end-points is an important component of the assessment, and it is generally believed that the most valid procedure in this evaluation is the measurement of drug self-administration. However, even this method rarely predicts the extent of abuse of a specific drug. Although methods are available which appear to measure relative abuse liability, these procedures are not validated for all drug classes. Thus, additional strategies, including abuse liability studies in humans, modelled after those used with animals, must be used in order to make a more informed prediction. Although there is pressure to place restrictions on new drugs at the time of marketing, in light of the difficulty of predicting relative abuse potential, a better strategy might be to market a drug without restrictions, but require postmarketing surveillance in order to obtain more accurate information on which to base a final decision.

  2. Sexual trajectories of abused and neglected youths.

    PubMed

    Brown, Jocelyn; Cohen, Patricia; Chen, Henian; Smailes, Elizabeth; Johnson, Jeffrey G

    2004-04-01

    The study objective was to examine whether childhood abuse or neglect is associated with the age of onset of puberty and sexual and romantic behavior. A cohort of children (the Children in the Community study) was randomly selected and studied prospectively from childhood to adulthood. A sample of 816 youths were interviewed in their homes at a mean age of 14, 16, and 22 years in 1983, from 1985 to 1986, and from 1991 to 1994. The outcome measures included age of menarche, signs of male puberty, first being in love, dating, sexual intercourse, and pregnancy reported by youths. Child abuse and neglect were measured by official records and youth reports. A history of two or more incidents of sexual abuse was significantly associated with early puberty and early pregnancy after gender, class, race, paternal absence, and mother's age at the birth of the study child were controlled statistically. Public education regarding risk for premature sexual behavior among youths who have experienced sexual abuse is warranted. Efforts to prevent teenage pregnancy should include monitoring and educating sexually abused children as they enter puberty.

  3. 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

  4. 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.

  5. A Practical Approach to Rural Drug Abuse Programming.

    ERIC Educational Resources Information Center

    Rozelle, George R.; And Others

    1980-01-01

    Reviews characteristics of rural drug abuse and general considerations for rural service delivery. Describes the Prevention Project, a rural drug abuse program in Florida, and explains its development, philosophy, and teaching techniques, including a basic educational module for use with rural youth. Includes recommendations for similar programs.…

  6. Developmental lead exposure induces opposite effects on ethanol intake and locomotion in response to central vs. systemic cyanamide administration.

    PubMed

    Mattalloni, Mara Soledad; Deza-Ponzio, Romina; Albrecht, Paula Alejandra; Cancela, Liliana Marina; Virgolini, Miriam Beatriz

    2017-02-01

    Lead (Pb) is a developmental neurotoxicant that elicits differential responses to drugs of abuse. Particularly, ethanol consumption has been demonstrated to be increased as a consequence of environmental Pb exposure, with catalase (CAT) and brain acetaldehyde (ACD, the first metabolite of ethanol) playing a role. The present study sought to interfere with ethanol metabolism by inhibiting ALDH2 (mitochondrial aldehyde dehydrogenase) activity in both liver and brain from control and Pb-exposed rats as a strategy to accumulate ACD, a substance that plays a major role in the drug's reinforcing and/or aversive effects. To evaluate the impact on a 2-h chronic voluntary ethanol intake test, developmentally Pb-exposed and control rats were administered with cyanamide (CY, an ALDH inhibitor) either systemically or intracerebroventricularly (i.c.v.) on the last 4 sessions of the experiment. Furthermore, on the last session and after locomotor activity was assessed, all animals were sacrificed to obtain brain and liver samples for ALDH2 and CAT activity determination. Systemic CY administration reduced the elevated ethanol intake already reported in the Pb-exposed animals (but not in the controls) accompanied by liver (but not brain) ALDH2 inactivation. On the other hand, a 0.3 mg i.c.v. CY administration enhanced both ethanol intake and locomotor activity accompanied by brain ALDH2 inactivation in control animals, while an increase in ethanol consumption was also observed in the Pb-exposed group, although in the absence of brain ALDH2 blockade. No changes were observed in CAT activity as a consequence of CY administration. These results support the participation of liver and brain ACD in ethanol intake and locomotor activity, responses that are modulated by developmental Pb exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. High-Octane Mid-Level Ethanol Blend Market Assessment

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

    Johnson, Caley; Newes, Emily; Brooker, Aaron

    2015-12-01

    The United States government has been promoting increased use of biofuels, including ethanol from non-food feedstocks, through policies contained in the Energy Independence and Security Act of 2007. The objective is to enhance energy security, reduce greenhouse gas (GHG) emissions, and provide economic benefits. However, the United States has reached the ethanol blend wall, where more ethanol is produced domestically than can be blended into standard gasoline. Nearly all ethanol is blended at 10 volume percent (vol%) in gasoline. At the same time, the introduction of more stringent standards for fuel economy and GHG tailpipe emissions is driving research tomore » increase the efficiency of spark ignition (SI) engines. Advanced strategies for increasing SI engine efficiency are enabled by higher octane number (more highly knock-resistant) fuels. Ethanol has a research octane number (RON) of 109, compared to typical U.S. regular gasoline at 91-93. Accordingly, high RON ethanol blends containing 20 vol% to 40 vol% ethanol are being extensively studied as fuels that enable design of more efficient engines. These blends are referred to as high-octane fuel (HOF) in this report. HOF could enable dramatic growth in the U.S. ethanol industry, with consequent energy security and GHG emission benefits, while also supporting introduction of more efficient vehicles. HOF could provide the additional ethanol demand necessary for more widespread deployment of cellulosic ethanol. However, the potential of HOF can be realized only if it is adopted by the motor fuel marketplace. This study assesses the feasibility, economics, and logistics of this adoption by the four required participants--drivers, vehicle manufacturers, fuel retailers, and fuel producers. It first assesses the benefits that could motivate these participants to adopt HOF. Then it focuses on the drawbacks and barriers that these participants could face when adopting HOF and proposes strategies--including incentives

  8. The determination of ethanol in blood and urine by mass fragmentography

    NASA Technical Reports Server (NTRS)

    Pereira, W. E.; Summons, R. E.; Rindfleisch, T. C.; Duffield, A. M.

    1974-01-01

    A mass fragmentographic technique for a rapid, specific and sensitive determination of ethanol in blood and urine is described. A Varian gas chromatograph coupled through an all-glass membrane separator to a Finnigan quadripole mass spectrometer and interfaced to a computer system is used for ethanol determination in blood and urine samples. A procedure for plotting calibration curves for ethanol quantitation is also described. Quantitation is achieved by plotting the peak area ratios of undeuterated-to-deuterated ethanol fragment ions against the amount of ethanol added. Representative results obtained by this technique are included.

  9. Adaptation to High Ethanol Reveals Complex Evolutionary Pathways

    PubMed Central

    Das, Anupam; Espinosa-Cantú, Adriana; De Maeyer, Dries; Arslan, Ahmed; Van Pee, Michiel; van der Zande, Elisa; Meert, Wim; Yang, Yudi; Zhu, Bo; Marchal, Kathleen; DeLuna, Alexander; Van Noort, Vera; Jelier, Rob; Verstrepen, Kevin J.

    2015-01-01

    Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts. PMID:26545090

  10. Neonatal ethanol exposure from ethanol-based hand sanitisers in isolettes.

    PubMed

    Hsieh, Shizuka; Sapkota, Amir; Wood, Rebecca; Bearer, Cynthia; Kapoor, Shiv

    2018-01-01

    The aims of this study is to measure the ethanol vapours in the isolette after use of hands cleaned with ethanol-based hand sanitiser (EBHS). Two squirts (1.5 mL) of hand sanitiser were rubbed on hands for 10 or 20 s before inserting the hands in the isolette for 5 min. Ethanol vapours were measured in the isolette with photoionisation detector and alcohol breathalyser for 30 min. Peak ethanol concentration in the isolette was considerably higher with a 10 s hand rub (381±192 ppm) compared with a 20 s hand rub (99±50 ppm), and dissipated to ≤5 ppm within 30 min. Under routine care, EBHS use by care providers exposes neonates in isolettes to 3.7-7.3 or 1.4-2.8 mg/kg ethanol per day with 10 or 20 s hand rubs, respectively. The expected blood level from average single exposure is 0.036 mg/dL with 10 s hand rub and may increase further with multiple exposures in a short period. Preterm neonates in the isolette are at risk of inadvertent exposure to ethanol. The expected blood alcohol level from this exposure is small and below 1 mg/dL level recommended by European Medicines Agency to limit the ethanol exposure in children. The unintended ethanol exposure can be avoided by rubbing hands for at least 20 s after applying EBHS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Childhood Sexual Abuse. A Booklet for First Nations Adult Survivors.

    ERIC Educational Resources Information Center

    Samson, Alana; And Others

    This booklet offers information about sources of help for First Nations adult survivors of childhood sexual abuse, particularly in Canada. It explains the definition of sexual abuse and describes the specifics of the law regarding such abuse. Descriptions of common aspects of childhood sexual abuse include quotes from adult survivors. Long-term…

  12. Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminal chemosensory neurons to ethanol and its flavor components.

    PubMed

    Glendinning, John I; Tang, Joyce; Morales Allende, Ana Paula; Bryant, Bruce P; Youngentob, Lisa; Youngentob, Steven L

    2017-08-01

    Fetal alcohol exposure (FAE) leads to increased intake of ethanol in adolescent rats and humans. We asked whether these behavioral changes may be mediated in part by changes in responsiveness of the peripheral taste and oral trigeminal systems. We exposed the experimental rats to ethanol in utero by administering ethanol to dams through a liquid diet; we exposed the control rats to an isocaloric and isonutritive liquid diet. To assess taste responsiveness, we recorded responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to lingual stimulation with ethanol, quinine, sucrose, and NaCl. To assess trigeminal responsiveness, we measured changes in calcium levels of isolated trigeminal ganglion (TG) neurons during stimulation with ethanol, capsaicin, mustard oil, and KCl. Compared with adolescent control rats, the adolescent experimental rats exhibited diminished CT nerve responses to ethanol, quinine, and sucrose and GL nerve responses to quinine and sucrose. The reductions in taste responsiveness persisted into adulthood for quinine but not for any of the other stimuli. Adolescent experimental rats also exhibited reduced TG neuron responses to ethanol, capsaicin, and mustard oil. The lack of change in responsiveness of the taste nerves to NaCl and the TG neurons to KCl indicates that FAE altered only a subset of the response pathways within each chemosensory system. We propose that FAE reprograms development of the peripheral taste and trigeminal systems in ways that reduce their responsiveness to ethanol and surrogates for its pleasant (i.e., sweet) and unpleasant (i.e., bitterness, oral burning) flavor attributes. NEW & NOTEWORTHY Pregnant mothers are advised to avoid alcohol. This is because even small amounts of alcohol can alter fetal brain development and increase the risk of adolescent alcohol abuse. We asked how fetal alcohol exposure (FAE) produces the latter effect in adolescent rats by measuring responsiveness of taste nerves and trigeminal

  13. Neurofunctional Abnormalities during Sustained Attention in Severe Childhood Abuse.

    PubMed

    Lim, Lena; Hart, Heledd; Mehta, Mitul A; Simmons, Andrew; Mirza, Kah; Rubia, Katya

    2016-01-01

    Childhood maltreatment is associated with adverse affective and cognitive consequences including impaired emotion processing, inhibition and attention. However, the majority of functional magnetic resonance imaging (fMRI) studies in childhood maltreatment have examined emotion processing, while very few studies have tested the neurofunctional substrates of cognitive functions and none of attention. This study investigated the association between severe childhood abuse and fMRI brain activation during a parametric sustained attention task with a progressively increasing load of sustained attention in 21 medication-naïve, drug-free young people with a history of childhood abuse controlling for psychiatric comorbidities by including 19 psychiatric controls matched for psychiatric diagnoses, and 27 healthy controls. Behaviorally, the participants exposed to childhood abuse showed increased omission errors in the task which correlated positively trend-wise with the duration of their abuse. Neurofunctionally, the participants with a history of childhood abuse, but not the psychiatric controls, displayed significantly reduced activation relative to the healthy controls during the most challenging attention condition only in typical attention regions including left inferior and dorsolateral prefrontal cortex, insula and temporal areas. We therefore show for the first time that severe childhood abuse is associated with neurofunctional abnormalities in key ventral frontal-temporal sustained attention regions. The findings represent a first step towards the delineation of abuse-related neurofunctional abnormalities in sustained attention, which may help in the development of effective treatments for victims of childhood abuse.

  14. Neurofunctional Abnormalities during Sustained Attention in Severe Childhood Abuse

    PubMed Central

    Mehta, Mitul A.; Simmons, Andrew; Mirza, Kah; Rubia, Katya

    2016-01-01

    Childhood maltreatment is associated with adverse affective and cognitive consequences including impaired emotion processing, inhibition and attention. However, the majority of functional magnetic resonance imaging (fMRI) studies in childhood maltreatment have examined emotion processing, while very few studies have tested the neurofunctional substrates of cognitive functions and none of attention. This study investigated the association between severe childhood abuse and fMRI brain activation during a parametric sustained attention task with a progressively increasing load of sustained attention in 21 medication-naïve, drug-free young people with a history of childhood abuse controlling for psychiatric comorbidities by including 19 psychiatric controls matched for psychiatric diagnoses, and 27 healthy controls. Behaviorally, the participants exposed to childhood abuse showed increased omission errors in the task which correlated positively trend-wise with the duration of their abuse. Neurofunctionally, the participants with a history of childhood abuse, but not the psychiatric controls, displayed significantly reduced activation relative to the healthy controls during the most challenging attention condition only in typical attention regions including left inferior and dorsolateral prefrontal cortex, insula and temporal areas. We therefore show for the first time that severe childhood abuse is associated with neurofunctional abnormalities in key ventral frontal-temporal sustained attention regions. The findings represent a first step towards the delineation of abuse-related neurofunctional abnormalities in sustained attention, which may help in the development of effective treatments for victims of childhood abuse. PMID:27832090

  15. Educator Sexual Abuse: Two Case Reports

    ERIC Educational Resources Information Center

    Burgess, Ann Wolbert; Welner, Michael; Willis, Danny G.

    2010-01-01

    Sexual abuse by educators has become an increasingly noted type of sexual abuse, especially among adolescents, for two reasons. First, there is a potential for these cases to be silent and prolonged and second, when disclosed, the forensic implications usually include both criminal and/or civil sanctions. For forensic case evaluations,…

  16. Types of abuse and risk factors associated with elder abuse.

    PubMed

    Simone, Lacher; Wettstein, Albert; Senn, Oliver; Rosemann, Thomas; Hasler, Susann

    2016-01-01

    Detecting elder abuse is challenging because it is a taboo, and many cases remain unreported. This study aimed to identify types of elder abuse and to investigate its associated risk factors. Retrospective analyses of 903 dossiers created at an Independent Complaints Authority for Old Age in the Canton of Zurich, Switzerland, from January 1, 2008 to October 31, 2012. Characteristics of victims and perpetrators, types of abuse, and associated risk factors related to the victim or the perpetrator were assessed. Bi- and multivariate analysis were used to identify abuse and neglect determinants. A total of 150 cases reflected at least one form of elder abuse or neglect; 104 cases were categorised as abuse with at least one type of abuse (overall 135 mentions), 46 cases were categorised as neglect (active or passive). Psychological abuse was the most reported form (47%), followed by financial (35%), physical (30%) and anticonstitutional abuse (18%). In 81% of the 150 cases at least two risk factors existed. In 13% no associated risk factor could be identified. Compared with neglect, elders with abuse were less likely to be a nursing home resident than living at home (odds ratio [OR] 0.02, 95% confidence interval [CI] 0.00-0.19). In addition, they were more likely to be cohabiting with their perpetrators (OR 18.01, 95% CI 4.43-73.19). For the majority of the reported elder abuse cases at least two associated risk factors could be identified. Knowledge about these red flags and a multifaceted strategy are needed to identify and prevent elder abuse.

  17. Method and system for ethanol production

    DOEpatents

    Feder, H.M.; Chen, M.J.

    1980-05-21

    A transition metal carbonyl and a tertiary amine are employed as a homogeneous catalytic system in methanol or a less volatile solvent to react methanol with carbon monoxide and hydrogen gas producing ethanol and carbon dioxide. The gas contains a high carbon monoxide to hydrogen ratio as is present in a typical gasifier product. The reaction has potential for anhydrous ethanol production as carbon dioxide rather than water is produced. The only other significant by-product is methane. Selected transition metal carbonyls include those of iron, ruthenium and possibly manganese and osmium. Selected amines include trimethylamine, N-Methylpyrrolidine, 24-diazabicyclooctane, dimethyneopentylamine and 2-pryidinol.

  18. Method and system for ethanol production

    DOEpatents

    Feder, Harold M.; Chen, Michael J.

    1981-01-01

    A transition metal carbonyl and a tertiary amine are employed as a homogeneous catalytic system in methanol or a less volatile solvent to react methanol with carbon monoxide and hydrogen gas producing ethanol and carbon dioxide. The gas contains a high carbon monoxide to hydrogen ratio as is present in a typical gasifier product. The reaction has potential for anhydrous ethanol production as carbon dioxide rather than water is produced. The only other significant by product is methane. Selected transition metal carbonyls include those of iron, ruthenium and possibly manganese and osmium. Selected amines include trimethylamine, N-Methylpyrrolidine, 24-diazabicyclooctane, dimethyneopentylamine and 2-pryidinol.

  19. Method and system for ethanol production

    DOEpatents

    Feder, Harold M.; Chen, Michael J.

    1983-01-01

    A transition metal carbonyl and a tertiary amine are employed as a homogeneous catalytic system in methanol or a less volatile solvent to react methanol with carbon monoxide and hydrogen gas producing ethanol and carbon dioxide. The gas contains a high carbon monoxide to hydrogen ratio as is present in a typical gasifier product. The reaction has potential for anhydrous ethanol production as carbon dioxide rather than water is produced. Selected transition metal carbonyls include those of iron, rhodium ruthenium, manganese in combination with iron and possibly osmium. Selected amines include trimethylamine, N-Methylpyrrolidine, 2,4-diazabicyclooctane, dimethylneopentylamine, N-methylpiperidine and derivatives of N-methylpiperidine.

  20. Method and system for ethanol production

    DOEpatents

    Feder, H.M.; Chen, M.J.

    1981-09-24

    A transition metal carbonyl and a tertiary amine are employed as a homogeneous catalytic system in methanol or a less volatile solvent to react methanol with carbon monoxide and hydrogen gas producing ethanol and carbon dioxide. The gas contains a high carbon monoxide to hydrogen ratio as is present in a typical gasifier product. The reaction has potential for anhydrous ethanol production as carbon dioxide rather than water is produced. Selected transition metal carbonyls include those of iron, rhodium, ruthenium, manganese in combination with iron and possibly osmium. Selected amines include trimethylamine, N-Methylpyrrolidine, 2,4-diazabicyclooctane, dimethylneopentylamine, N-methylpiperidine and derivatives of N-methylpiperidine.

  1. The induction of cytochrome P450 2E1 by ethanol leads to the loss of synaptic proteins via PPARα down-regulation.

    PubMed

    Na, Shufang; Li, Jie; Zhang, Huibo; Li, Yueran; Yang, Zheqiong; Zhong, Yanjun; Dong, Guicheng; Yang, Jing; Yue, Jiang

    2017-06-15

    Ethanol, one of the most commonly abused substances throughout history, is a substrate and potent inducer of cytochrome P450 2E1 (CYP2E1). Our previous study showed that brain CYP2E1 was induced by chronic ethanol treatment and was associated with ethanol-induced neurotoxicity in rats. We therefore investigated the possible mechanism of brain CYP2E1 involvement in ethanol-induced neurodegeneration. Compared with the controls, chronic ethanol treatment (3.0g/kg, i.g., 160days) significantly increased CYP2E1 mRNA levels in the rat cortex, but the mRNA levels of peroxisome proliferator-activated receptor α (PPARα) and the pre- and post-synaptic proteins (synaptophysin, SYP, and drebrin1, DBN1) were decreased. Ethanol treatment dose-dependently induced CYP2E1 mRNA expression, and CYP2E1 overexpression exacerbated the ethanol-induced neurotoxicity. Pretreatment with p38 inhibitor (SB202190) and ERK1/2 inhibitor (U0126) attenuated the induction of CYP2E1 mRNA and protein levels by ethanol; however, no change was observed with JNK inhibitor pretreatment. Ethanol exposure or CYP2E1 overexpression significantly decreased PPARα, SYP, and DBN1 expression as indicated by the data from real-time RT-PCR, Western blotting and immunocytochemistry. The activation of PPARα by WY14643 increased the activity of the SYP and DBN1 promoters and attenuated the inhibition of these genes by ethanol. The specific siRNA for CYP2E1 significantly attenuated the ethanol-induced inhibition of PPARα, SYP and DBN1 mRNA levels. These results suggest that the induction of CYP2E1 by ethanol may be mediated via the p38 and ERK1/2 signaling pathways in neurons but not via the JNK pathway. The CYP2E1-PPARα axis may play a role in ethanol-induced neurotoxicity via the alteration of the genes related with synaptic function. Copyright © 2017. Published by Elsevier B.V.

  2. Benefits and Limits of Abuse-Deterrent Painkillers.

    PubMed

    Hendrikson, Hollie; Hanson, Karmen

    2016-02-01

    Abuse of opioid prescription products, meant to reduce pain, has been making headlines in recent years as a growing problem not only in rural and urban areas, but also across population groups. Policymakers looking for effective ways to reduce such abuse are employing various strategies, including setting up prescription drug monitoring programs. Another approach gaining attention involves encouraging or requiring the use of prescription drug formulas that can help deter abuse of opioid painkiller products.

  3. Interleukin-32γ attenuates ethanol-induced liver injury by the inhibition of cytochrome P450 2E1 expression and inflammatory responses.

    PubMed

    Lee, Dong Hun; Kim, Dae Hwan; Hwang, Chul Ju; Song, Sukgil; Han, Sang Bae; Kim, Youngsoo; Yoo, Hwan Soo; Jung, Young Suk; Kim, Soo Hyun; Yoon, Do Young; Hong, Jin Tae

    2015-05-01

    Alcohol abuse and alcoholism lead to alcoholic liver disease (ALD), which is a major type of chronic liver disease worldwide. Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. However, the role of IL-32 in chronic liver disease has not been reported. In the present paper, we tested the effect of IL-32γ on ethanol-induced liver injury in IL-32γ-overexpressing transgenic mice (IL-32γ mice) after chronic ethanol feeding. Male C57BL/6 and IL-32γ mice (10-12 weeks old) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 6 weeks. IL-32γ-transfected HepG2 and Huh7 cells, as well as primary hepatocytes from IL-32γ mice, were treated with or without ethanol. The hepatic steatosis and damage induced by ethanol administration were attenuated in IL-32γ mice. Ethanol-induced cytochrome P450 2E1 expression and hydrogen peroxide levels were decreased in the livers of IL-32γ mice, primary hepatocytes from IL-32γ mice and IL-32γ-overexpressing human hepatic cells. The ethanol-induced expression levels of cyclo-oxygenase-2 (COX-2) and IL-6 were reduced in the livers of IL-32γ mice. Because nuclear transcription factor κB (NF-κB) is a key redox transcription factor of inflammatory responses, we examined NF-κB activity. Ethanol-induced NF-κB activities were significantly lower in the livers of IL-32γ mice than in wild-type (WT) mice. Furthermore, reduced infiltration of natural killer cells, cytotoxic T-cells and macrophages in the liver after ethanol administration was observed in IL-32γ mice. These data suggest that IL-32γ prevents ethanol-induced hepatic injury via the inhibition of oxidative damage and inflammatory responses.

  4. Updates to the Corn Ethanol Pathway and Development of an Integrated Corn and Corn Stover Ethanol Pathway in the GREET™ Model

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

    Wang, Zhichao; Dunn, Jennifer B.; Wang, Michael Q.

    Corn ethanol, a first-generation biofuel, is the predominant biofuel in the United States. In 2013, the total U.S. ethanol fuel production was 13.3 billion gallons, over 95% of which was produced from corn (RFA, 2014). The 2013 total renewable fuel mandate was 16.6 billion gallons according to the Energy Independence and Security Act (EISA) (U.S. Congress, 2007). Furthermore, until 2020, corn ethanol will make up a large portion of the renewable fuel volume mandated by Renewable Fuels Standard (RFS2). For the GREET1_2014 release, the corn ethanol pathway was subject to updates reflecting changes in corn agriculture and at corn ethanolmore » plants. In the latter case, we especially focused on the incorporation of corn oil as a corn ethanol plant co-product. Section 2 covers these updates. In addition, GREET now includes options to integrate corn grain and corn stover ethanol production on the field and at the biorefinery. These changes are the focus of Section 3.« less

  5. Subtypes of cocaine abusers.

    PubMed

    Weiss, R D; Mirin, S M

    1986-09-01

    We have characterized five subtypes of cocaine abusers on the basis of clinical presentation, family history data, and response to specific treatment interventions. These include depressed patients who value the euphorigenic effects of the drug, patients with bipolar or cyclothymic disorder who use cocaine to augment manic or hypomanic symptoms or to alleviate depression, adults with ADD, residual type, who find that cocaine has a paradoxical effect of increasing attention span and decreasing motor restlessness, patients with narcissistic and borderline personality disorders who use cocaine for its social prestige and because it bolsters self-esteem, and patients with antisocial personality disorder who use cocaine as part of an overall pattern of antisocial behavior. Although not all cocaine abusers fit neatly into these categories, careful psychiatric evaluation and subtyping is essential in designing a specific treatment program for these patients. As the prevalence rate of cocaine abuse increases, studies that examine the efficacy of various treatment approaches for specific subtypes of cocaine abusers will be essential. It is hoped that our work will be a step in that direction.

  6. Substance Abuse Among Blacks Across the Diaspora

    PubMed Central

    Lacey, Krim K.; Mouzon, Dawne M.; Govia, Ishtar O.; Matusko, Niki; Forsythe-Brown, Ivy; Abelson, Jamie M.; Jackson, James S.

    2016-01-01

    Background Lower rates of substance abuse are found among Black Americans compared to Whites, but little is known about differences in substance abuse across ethnic groups within the black population. Objectives We examined prevalence rates of substance abuse among Blacks across three geographic regions (US, Jamaica, Guyana). The study also sought to ascertain whether length of time, national context and major depressive episodes (MDE) were associated with substance abuse. Methods We utilized three different data sources based upon probability samples collected in three different countries. The samples included 3,570 African Americans and 1,621 US Caribbean Black adults from the 2001–2003 National Survey of American Life (NSAL). An additional 1,142 Guyanese Blacks and 1,176 Jamaican Blacks living in the Caribbean region were included from the 2005 NSAL replication extension study, Family Connections Across Generations and Nations (FCGN). Mental disorders were based upon DSM-IV criteria. For the analysis, we used descriptive statistics, chi-square, and multivariate logistic regression analytic procedures. Results Prevalence of substance abuse varied by national context, with higher rates among Blacks within the United States compared to the Caribbean region. Rates of substance abuse were lower overall for women, but differ across cohorts by nativity and length of time in the United States, and in association with major depressive episode. Conclusions The study highlights the need for further examination of how substance abuse disparities between US-based and Caribbean-based populations may become manifested. PMID:27191862

  7. Ethanol immunosuppression in vitro

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

    Kaplan, D.R.

    Ethanol in concentrations equivalent to levels achieved by the ingestion of moderate to large amounts of alcoholic beverages has been shown to inhibit mitogen and anti-CD3 stimulated human T lymphocyte proliferation. This inhibition was monophasic suggesting that ethanol affected a single limiting component of T cell proliferation. In experiments designed to test the effect of ethanol on various aspects of proliferation, it was demonstrated that ethanol inhibited the capacity of exogenously supplied interleukin 2 to stimulate proliferation of T cells that had previously acquired interleukin 2 receptors in a monophasic, dose-dependent manner. Moreover, there was no suppression of interleukin 2more » production or interleukin 2 receptor acquisition. Thus, ethanol was shown to mediate immunosuppression by a mechanism specific to one component of proliferation. Additive inhibition of T cell proliferation was seen with ethanol plus cyclosporin A which inhibits interleukin 2 production. The level of inhibition with 250 ng/ml cyclosporin A alone was equivalent to the level seen with 62 ng/ml cyclosporin A plus 20 mM (94 mg%) ethanol. Ethanol also suppressed an immune effector mechanism. NK cytotoxicity was depressed in a monophasic, dose-dependent manner. Thus, ethanol might be considered as a possible adjunct in immunosuppressive therapy.« less

  8. Exploring Taboos: Comparing Male- and Female-Perpetrated Child Sexual Abuse

    ERIC Educational Resources Information Center

    Peter, Tracey

    2009-01-01

    The objective of this article is to compare male- and female-perpetrated sexual abuse in terms of victim and abuser characteristics, type of abuse, family structure, and worker information. Bivariate tests of significance were performed on the 1998 Canadian Incidence Study of Reported Child Abuse and Neglect, which included 308 male and 37 female…

  9. Repeated light-dark phase shifts modulate voluntary ethanol intake in male and female high alcohol-drinking (HAD1) rats.

    PubMed

    Clark, James W; Fixaris, Michael C; Belanger, Gabriel V; Rosenwasser, Alan M

    2007-10-01

    Chronic disruption of sleep and other circadian biological rhythms, such as occurs in shift work or in frequent transmeridian travel, appears to represent a significant source of allostatic load, leading to the emergence of stress-related physical and psychological illness. Recent animal experiments have shown that these negative health effects may be effectively modeled by exposure to repeated phase shifts of the daily light-dark (LD) cycle. As chronobiological disturbances are thought to promote relapse in abstinent alcoholics, and may also be associated with increased risk of subsequent alcohol abuse in nonalcoholic populations, the present experiment was designed to examine the effects of repeated LD phase shifts on voluntary ethanol intake in rats. A selectively bred, high alcohol-drinking (HAD1) rat line was utilized to increase the likelihood of excessive alcoholic-like drinking. Male and female rats of the selectively bred HAD1 rat line were maintained individually under a LD 12:12 cycle with both ethanol (10% v/v) and water available continuously. Animals in the experimental group were subjected to repeated 6-hour LD phase advances at 3 to 4 week intervals, while control rats were maintained under a stable LD cycle throughout the study. Contact-sensing drinkometers were used to monitor circadian lick patterns, and ethanol and water intakes were recorded weekly. Control males showed progressively increasing ethanol intake and ethanol preference over the course of the study, but males exposed to chronic LD phase shifts exhibited gradual decreases in ethanol drinking. In contrast, control females displayed decreasing ethanol intake and ethanol preference over the course of the experiment, while females exposed to experimental LD phase shifts exhibited a slight increase in ethanol drinking. Chronic circadian desynchrony induced by repeated LD phase shifts resulted in sex-specific modulation of voluntary ethanol intake, reducing ethanol intake in males while

  10. Correlates of cyber dating abuse among teens.

    PubMed

    Zweig, Janine M; Lachman, Pamela; Yahner, Jennifer; Dank, Meredith

    2014-08-01

    Recent advancements in technology (e.g., social networking, texting) have created new ways for dating youth to relate to one another, including in abusive ways via "cyber dating abuse." Cyber dating abuse is a form of teen dating violence that overlaps with other types of abuse (e.g., psychological) but also has several unique characteristics. Given the phenomenon's limited presence in dating violence literature, we focus on identifying how experiencing cyber dating abuse relates to youths' individual behaviors and experiences (e.g., substance use, sexual activity), psychosocial adjustment, school connection, family relationships, and partner relationships. A total of 3,745 youth (52% female, 74% White) in three northeastern states participated in the survey and reported currently being in a dating relationship or having been in one during the prior year. We found that experiences of cyber dating abuse were most significantly correlated with being female, committing a greater variety of delinquent behaviors, having had sexual activity in one's lifetime, having higher levels of depressive symptoms, and having higher levels of anger/hostility. Further, cyber dating abuse appeared somewhat more strongly related to depressive symptoms and delinquency than did other forms of teen dating violence and abuse.

  11. Repeated Binge-Like Ethanol Drinking Alters Ethanol Drinking Patterns and Depresses Striatal GABAergic Transmission

    PubMed Central

    Wilcox, Mark V; Carlson, Verginia C Cuzon; Sherazee, Nyssa; Sprow, Gretchen M; Bock, Roland; Thiele, Todd E; Lovinger, David M; Alvarez, Veronica A

    2014-01-01

    Repeated cycles of binge alcohol drinking and abstinence are key components in the development of dependence. However, the precise behavioral mechanisms underlying binge-like drinking and its consequences on striatal synaptic physiology remain unclear. In the present study, ethanol and water drinking patterns were recorded with high temporal resolution over 6 weeks of binge-like ethanol drinking using the ‘drinking in the dark' (DID) protocol. The bottle exchange occurring at the beginning of each session prompted a transient increase in the drinking rate that might facilitate the acquisition of ethanol binge-like drinking. Ethanol drinking mice also displayed a ‘front-loading' behavior, in which the highest rate of drinking was recorded during the first 15 min. This rate increased over weeks and paralleled the mild escalation of blood ethanol concentrations. GABAergic and glutamatergic transmission in the dorsal striatum were examined following DID. Spontaneous glutamatergic transmission and the density of dendritic spines were unchanged after ethanol drinking. However, the frequency of GABAA receptor-mediated inhibitory postsynaptic currents was depressed in medium spiny neurons of ethanol drinking mice. A history of ethanol drinking also increased ethanol preference and altered the acute ethanol effects on GABAergic transmission differentially in dorsolateral and dorsomedial striatum. Together, the study shows that the bottle exchange during DID promotes fast, voluntary ethanol drinking and that this intermittent pattern of ethanol drinking causes a depression of GABAergic transmission in the dorsal striatum. PMID:23995582

  12. The allostatic impact of chronic ethanol on gene expression: A genetic analysis of chronic intermittent ethanol treatment in the BXD cohort

    PubMed Central

    van der Vaart, Andrew D.; Wolstenholme, Jennifer T.; Smith, Maren L.; Harris, Guy M.; Lopez, Marcelo F.; Wolen, Aaron R.; Becker, Howard C.; Williams, Robert W.; Miles, Michael F.

    2016-01-01

    The transition from acute to chronic ethanol exposure leads to lasting behavioral and physiological changes such as increased consumption, dependence, and withdrawal. Changes in brain gene expression are hypothesized to underlie these adaptive responses to ethanol. Previous studies on acute ethanol identified genetic variation in brain gene expression networks and behavioral responses to ethanol across the BXD panel of recombinant inbred mice. In this work, we have performed the first joint genetic and genomic analysis of transcriptome shifts in response to chronic intermittent ethanol (CIE) by vapor chamber exposure in a BXD cohort. CIE treatment is known to produce significant and sustained changes in ethanol consumption with repeated cycles of ethanol vapor. Using Affymetrix microarray analysis of prefrontal cortex (PFC) and nucleus accumbens (NAC) RNA, we compared CIE expression responses to those seen following acute ethanol treatment, and to voluntary ethanol consumption. Gene expression changes in PFC and NAC after CIE overlapped significantly across brain regions and with previously published expression following acute ethanol. Genes highly modulated by CIE were enriched for specific biological processes including synaptic transmission, neuron ensheathment, intracellular signaling, and neuronal projection development. Expression quantitative trait locus (eQTL) analyses identified genomic loci associated with ethanol-induced transcriptional changes with largely distinct loci identified between brain regions. Correlating CIE-regulated genes to ethanol consumption data identified specific genes highly associated with variation in the increase in drinking seen with repeated cycles of CIE. In particular, multiple myelin-related genes were identified. Furthermore, genetic variance in or near dynamin3 (Dnm3) on Chr1 at ~164 Mb may have a major regulatory role in CIE-responsive gene expression. Dnm3 expression correlates significantly with ethanol consumption, is

  13. Drug Abuse. A Guide for Parents and Teachers.

    ERIC Educational Resources Information Center

    St. Souver, F. Gerald; Plunkett, Thomas G.

    This booklet is concerned with providing information on drug abuse. A brief history of drug traffic and today's problem begin the pamphlet. The second part discusses the identification of drugs including opium, heroin, and marihuana. The next section is concerned with non-narcotic drug abuse, including Lysergic Acid Diethylamide (LSD) mascaline,…

  14. Suicide attempts among men with histories of child sexual abuse: examining abuse severity, mental health, and masculine norms.

    PubMed

    Easton, Scott D; Renner, Lynette M; O'Leary, Patrick

    2013-06-01

    Men who were sexually abused during childhood are at risk for a variety of long-term mental health problems, including suicidality. However, little is known about which factors are related to recent suicide attempts for this vulnerable, under-researched population. The purpose of this study was to examine the relationship between abuse severity, mental health, masculine norms and recent suicide attempts among men with histories of child sexual abuse (CSA). We analyzed survey data gathered from a purposive sample of 487 men who were sexually abused during childhood. The age of the sample ranged from 19 to 84 years (μ = 50.4 years). Recent suicide attempts served as the dependent variable in the study. Self-reported measures of sexual abuse severity, child physical abuse, mental health, masculine norms, and demographic information (age, race) represented the independent variables. The results from logistic regression modeling found that five variables - duration of the sexual abuse, use of force during the sexual abuse, high conformity to masculine norms, level of depressive symptoms, and suicidal ideation - increased the odds of a suicide attempt in the past 12 months. To improve mental health services for men with histories of CSA, mental health practitioners should incorporate sexual abuse severity, current mental health, and adherence to masculine norms into assessment and treatment planning. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. [Child abuse in the family].

    PubMed

    De Almeida, Helena Nunes; André, Isabel Margarida; De Almeida, Ana Nunes

    2002-01-01

    The objective of this study is to carry out a current survey of the situation of child abuse in the family. It is based on a national survey conducted in 1996, which was addressed to childcare professionals (in the areas of health, education and social services). This survey was based, on the one hand, on a wide-ranging definition of child abuse, including within it not just active forms of physical and psychic violence against the child, but also forms of (both material and affective) privation, omission or negligence which affect the child's growth and development. On the other hand, this study also favoured a contextual approach to child abuse. 1,126 institutions in Portugal were contacted and 755 valid survey responses were received. This report outlines some of the results obtained, namely by providing a description of the sample of the 755 child abuse victims, the respective social and family contexts to which they and the aggressors belong, as well as the types of abuse which have been committed against them; and a typology of forms of abuse and negligence, describing not just the internal aspects that make up child abuse directly, but also its relationship to the child's social and family contexts of belonging. The typology was derived from the statistical handling of the data gathered (factorial analysis of multiple matches, followed by a hierarchical analysis into clusters). A number of key concepts are summarised in the conclusion. Children of all age groups and of both sexes, and from all types of families and social backgrounds, regardless of their place in the phratry, are subject to abuse in Portugal. But different types of abuse and negligence are associated with the contexts to which the children and their families belong. Healthcare professionals are irreplaceable when it comes to detecting the wide variety of types of child abuse, and are an essential look-out post for two types of abuse which often slip through the net of other professionals

  16. The reinforcing properties of ethanol are quantitatively enhanced in adulthood by peri-adolescent ethanol, but not saccharin, consumption in female alcohol-preferring (P) rats.

    PubMed

    Toalston, Jamie E; Deehan, Gerald A; Hauser, Sheketha R; Engleman, Eric A; Bell, Richard L; Murphy, James M; McBride, William J; Rodd, Zachary A

    2015-08-01

    Alcohol drinking during adolescence is associated in adulthood with heavier alcohol drinking and an increased rate of alcohol dependence. Past research in our laboratory has indicated that peri-adolescent ethanol consumption can enhance the acquisition and reduce the rate of extinction of ethanol self-administration in adulthood. Caveats of the past research include reinforcer specificity, increased oral consumption during peri-adolescence, and a lack of quantitative assessment of the reinforcing properties of ethanol. The current experiments were designed to determine the effects of peri-adolescent ethanol or saccharin drinking on acquisition and extinction of oral ethanol self-administration and ethanol seeking, and to quantitatively assess the reinforcing properties of ethanol (progressive ratio). Ethanol or saccharin access by alcohol-preferring (P) rats occurred during postnatal day (PND) 30-60. Animals began operant self-administration of ethanol or saccharin after PND 85. After 10 weeks of daily operant self-administration, rats were tested in a progressive ratio paradigm. Two weeks later, self-administration was extinguished in all rats. Peri-adolescent ethanol consumption specifically enhanced the acquisition of ethanol self-administration, reduced the rate of extinction for ethanol self-administration, and quantitatively increased the reinforcing properties of ethanol during adulthood. Peri-adolescent saccharin consumption was without effect. The data indicate that ethanol consumption during peri-adolescence results in neuroadaptations that may specifically enhance the reinforcing properties of ethanol during adulthood. This increase in the reinforcing properties of ethanol could be a part of biological sequelae that are the basis for the effects of adolescent alcohol consumption on the increase in the rate of alcoholism during adulthood. Published by Elsevier Inc.

  17. Intoxication by gamma hydroxybutyrate and related analogues: Clinical characteristics and comparison between pure intoxication and that combined with other substances of abuse.

    PubMed

    Miró, Òscar; Galicia, Miguel; Dargan, Paul; Dines, Alison M; Giraudon, Isabelle; Heyerdahl, Fridtjof; Hovda, Knut E; Yates, Christopher; Wood, David M; Liakoni, Evangelia; Liechti, Matthias; Jürgens, Gesche; Pedersen, Carsten Boe; O'Connor, Niall; Markey, Gerard; Moughty, Adrian; Lee, Christopher; O'Donohoe, Patrick; Sein Anand, Jacek; Puiguriguer, Jordi; Homar, Catalina; Eyer, Florian; Vallersnes, Odd Martin; Persett, Per Sverre; Chevillard, Lucie; Mégarbane, Bruno; Paasma, Raido; Waring, W Stephen; Põld, Kristiina; Rabe, Christian; Kabata, Piotr Maciej

    2017-08-05

    To study the profile of European gamma-hydroxybutyrate (GHB) and gammabutyrolactone (GBL) intoxication and analyse the differences in the clinical manifestations produced by intoxication by GHB/GBL alone and in combination with other substances of abuse. We prospectively collected data on all the patients attended in the Emergency Departments (ED) of the centres participating in the Euro-DEN network over 12 months (October 2013 to September 2014) with a primary presenting complaint of drug intoxication (excluding ethanol alone) and registered the epidemiological and clinical data and outcomes. We included 710 cases (83% males, mean age 31 years), representing 12.6% of the total cases attended for drug intoxication. Of these, 73.5% arrived at the ED by ambulance, predominantly during weekend, and 71.7% consumed GHB/GBL in combination with other substances of abuse, the most frequent additional agents being ethanol (50%), amphetamine derivatives (36%), cocaine (12%) and cannabis (8%). Among 15 clinical features pre-defined in the project database, the 3 most frequently identified were altered behaviour (39%), reduced consciousness (34%) and anxiety (14%). The severity ranged from mild cases requiring no treatment (308 cases, 43.4%) to severe cases requiring admission to intensive care (103 cases, 14.6%) and mechanical ventilation (49 cases, 6.9%). No deaths were reported. In comparison with only GHB/GBL consumption, patients consuming GHB/GBL with co-intoxicants presented more vomiting (15% vs. 3%, p<0.001) and cardiovascular symptoms (5.3% vs. 1.5%, p<0.05), a greater need for treatment (59.8% vs. 48.3%, p<0.01) and a longer ED stay (11.3% vs. 3.6% patients with ED stay >12h, p<0.01). The profile of the typical GHB/GBL-intoxicated European is a young male, requiring care for altered behaviour and reduced level of consciousness, mainly during the weekend. The clinical features are more severe when GHB is consumed in combination with other substances of abuse

  18. Adolescent Abuse.

    ERIC Educational Resources Information Center

    Foreman, Susan; Seligman, Linda

    1983-01-01

    Discusses legal and developmental aspects of adolescent abuse, as distinguished from child abuse. The role of the school counselor in identifying and counseling abused adolescents and their families is discussed and several forms of intervention and support services are described. (JAC)

  19. Pathway engineering to improve ethanol production by thermophilic bacteria

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

    Lynd, L.R.

    1998-12-31

    Continuation of a research project jointly funded by the NSF and DOE is proposed. The primary project goal is to develop and characterize strains of C. thermocellum and C. thermosaccharolyticum having ethanol selectivity similar to more convenient ethanol-producing organisms. An additional goal is to document the maximum concentration of ethanol that can be produced by thermophiles. These goals build on results from the previous project, including development of most of the genetic tools required for pathway engineering in the target organisms. As well, we demonstrated that the tolerance of C. thermosaccharolyticum to added ethanol is sufficiently high to allow practicalmore » utilization should similar tolerance to produced ethanol be demonstrated, and that inhibition by neutralizing agents may explain the limited concentrations of ethanol produced in studies to date. Task 1 involves optimization of electrotransformation, using either modified conditions or alternative plasmids to improve upon the low but reproducible transformation, frequencies we have obtained thus far.« less

  20. Association for medical education and research in substance abuse.

    PubMed

    Samet, Jeffrey H; Galanter, Marc; Bridden, Carly; Lewis, David C

    2006-01-01

    The Association for Medical Education and Research in Substance Abuse (AMERSA) is a multi-disciplinary organization committed to health professional faculty development in substance abuse. In 1976, members of the Career Teachers Training Program in Alcohol and Drug Abuse, a US federally funded multi-disciplinary faculty development program, formed AMERSA. The organization grew from 59 founding members, who were primarily medical school faculty, to over 300 health professionals from a spectrum of disciplines including physicians, nurses, social workers, dentists, allied health professionals, psychologists and other clinical educators who are responsible for advancing substance abuse education. AMERSA members promote substance abuse education among health professionals by developing curricula, promulgating relevant policy and training health professional faculty to become excellent teachers in this field. AMERSA influences public policy by offering standards for improving substance abuse education. The organization publishes a peer-reviewed, quarterly journal, Substance Abuse, which emphasizes research on the education and training of health professions and also includes original clinical and prevention research. Each year, the AMERSA National Conference brings together researchers and health professional educators to learn about scientific advances and exemplary teaching approaches. In the future, AMERSA will continue to pursue this mission of advancing and supporting health professional faculty who educate students and trainees to address substance abuse in patients and clients.

  1. The relationship between childhood sexual abuse and alcohol abuse in women--a case-control study.

    PubMed

    Fleming, J; Mullen, P E; Sibthorpe, B; Attewell, R; Bammer, G

    1998-12-01

    The aim of this paper was to examine the association between reporting childhood sexual abuse (CSA) and alcohol abuse in a community sample of women using multivariate analysis which took into account a range of potential confounding variables (such as a family history of alcoholism) and effect modifiers (such as having an alcoholic partner). A two-stage retrospective case-control study was used to investigate the relationship between reporting CSA and alcohol abuse in women. Seven hundred and ten women randomly selected from the Australian federal electoral rolls. The Alcohol Use Disorders Identification Test (AUDIT) was used to measure alcohol abuse. A series of questions based on those developed by Wyatt (1985) were used to ascertain the prevalence of CSA. The final model showed that the relationship between a history of CSA and alcohol abuse reflected a complex interaction between CSA and a range of other factors in a woman's background. CSA was not by itself a significant predictor of alcohol abuse (OR = 0.61; 95% CI = 0.31-1.20). However, a history of CSA became significant in combination with co-factors which included: having a mother who was perceived as cold and uncaring; having an alcoholic partner; and believing that alcohol is a sexual disinhibitor. This study indicates that CSA alone is not a causative factor in the development of alcohol abuse among women and highlights the importance of examining the family background of women with alcohol problems.

  2. Reduction of salt content of fish sauce by ethanol treatment.

    PubMed

    Liu, Yu; Xu, Ying; He, Xiaoxia; Wang, Dongfeng; Hu, Shiwei; Li, Shijie; Jiang, Wei

    2017-08-01

    Fish sauce is a traditional condiment in Southeast Asia, normally containing high concentration of salt. The solubility of salt is lower in ethanol than in water. In the present study, fish sauce was desalted by ethanol treatment (including the processes of ethanol addition, mixing, standing and rotary evaporation). The salt concentration of fish sauce decreased significantly from 29.72 to 19.72 g/100 mL when the treated ethanol concentration was 21% (v/v). The addition of more than 12% (v/v) of ethanol significantly reduced dry weight, total soluble nitrogen content and amino acids nitrogen content. Besides, the quality of fish sauce remained first grade if no more than 21% (v/v) of ethanol was used. Furthermore, sensory analyses showed that ethanol treatment significantly reduced the taste of salty and the odor of ammonia. This study demonstrates that ethanol treatment is a potential way to decrease salt content in fish sauce, which meanwhile limits the losses of nutritional and sensorial values within an acceptable range.

  3. Evaluation of the antidepressant, anxiolytic and memory-improving efficacy of aripiprazole and fluoxetine in ethanol-treated rats.

    PubMed

    Burda-Malarz, Kinga; Kus, Krzysztof; Ratajczak, Piotr; Czubak, Anna; Hardyk, Szymon; Nowakowska, Elżbieta

    2014-07-01

    Some study results indicate a positive effect of aripiprazole (ARI) on impaired cognitive functions caused by brain damage resulting from chronic EtOH abuse. However, other research shows that to manifest itself, an ARI antidepressant effect requires a combined therapy with another selective serotonin reuptake inhibitor antidepressant, namely, fluoxetine (FLX). The aim of this article was to assess antidepressant and anxiolytic effects of ARI as well as its effect on spatial memory in ethanol-treated (alcoholized) rats. On the basis of alcohol consumption pattern, groups of (1) ethanol-preferring rats, with mean ethanol intake above 50%, and (2) ethanol-nonpreferring rats (EtNPRs), with mean ethanol intake below 50% of total daily fluid intake, were formed. The group of EtNPRs was used for this study, subdivided further into three groups administered ARI, FLX and a combination of both, respectively. Behavioral tests such as Porsolt's forced swimming test, the Morris water maze test and the two-compartment exploratory test were employed. Behavioral test results demonstrated (1) no antidepressant effect of ARI in EtNPRs in subchronic treatment and (2) no procognitive effect of ARI and FLX in EtNPRs in combined single administration. Combined administration of both drugs led to an anxiogenic effect and spatial memory deterioration in study animals. ARI had no antidepressant effect and failed to improve spatial memory in rats. However, potential antidepressant, anxiolytic and procognitive properties of the drug resulting from its mechanism of action encourage further research aimed at developing a dose of both ARI and FLX that will prove such effects in alcoholized EtNPRs.

  4. Gender differences in abused children with and without disabilities.

    PubMed

    Sobsey, D; Randall, W; Parrila, R K

    1997-08-01

    Two questions were posed: (1) What are the proportions of boys and girls in various categories of substantiated child abuse? (2) Do the gender proportions differ for children with and without disabilities? Data collected by previous researchers from a demographically representative sample of U.S. child abuse reporting districts was analyzed. This included 1,249 case files involving 1,834 children. The number of girls and boys who did and did not have disabilities was identified for three age categories and for several categories of abuse. Chi-square analyses were used to determine whether there was a relationship between disability and gender for the various age and abuse categories. More boys were physically abused and neglected, but more girls were sexually abused. Boys with disabilities, however, were over-represented in all categories of abuse. Moreover, gender proportions among abused children with disabilities differed significantly from those found among other abused children. Although slightly more than half of abused children without disabilities were girls, 65% of abused children with disabilities were boys. Boys represented a significantly larger proportion of physically abused, sexually abused, and neglected children with disabilities than would be expected from their respective proportion of abused and neglected children without disabilities. Several possible explanations for the observed gender and disability status interaction are discussed.

  5. Abuse of Disabled Children in Ghana

    ERIC Educational Resources Information Center

    Kassah, Alexander Kwesi; Kassah, Bente Lilljan Lind; Agbota, Tete Kobla

    2012-01-01

    Even though disabled children are targets of various forms of abuse, such issues remain mostly undocumented open secrets in many countries including Ghana. The article is based on a qualitative data provided by three key informants. Six stories emerged from the data and are discussed in terms of four main forms of abuse. Labelling theories are…

  6. Metabolic engineering for improved production of ethanol by Corynebacterium glutamicum.

    PubMed

    Jojima, Toru; Noburyu, Ryoji; Sasaki, Miho; Tajima, Takahisa; Suda, Masako; Yukawa, Hideaki; Inui, Masayuki

    2015-02-01

    Recombinant Corynebacterium glutamicum harboring genes for pyruvate decarboxylase (pdc) and alcohol dehydrogenase (adhB) can produce ethanol under oxygen deprivation. We investigated the effects of elevating the expression levels of glycolytic genes, as well as pdc and adhB, on ethanol production. Overexpression of four glycolytic genes (pgi, pfkA, gapA, and pyk) in C. glutamicum significantly increased the rate of ethanol production. Overexpression of tpi, encoding triosephosphate isomerase, further enhanced productivity. Elevated expression of pdc and adhB increased ethanol yield, but not the rate of production. Fed-batch fermentation using an optimized strain resulted in ethanol production of 119 g/L from 245 g/L glucose with a yield of 95% of the theoretical maximum. Further metabolic engineering, including integration of the genes for xylose and arabinose metabolism, enabled consumption of glucose, xylose, and arabinose, and ethanol production (83 g/L) at a yield of 90 %. This study demonstrated that C. glutamicum has significant potential for the production of cellulosic ethanol.

  7. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

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

    Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, comparedmore » to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights:

  8. Psychiatric Disorders of Children Living with Drug-Abusing, Alcohol-Abusing, and Non-Substance-Abusing Fathers.

    ERIC Educational Resources Information Center

    Kelley, Michelle L.; Fals-Stewart, William

    2004-01-01

    Objective: The present study examined lifetime psychiatric disorders and current emotional and behavioral problems of 8- to 12-year-old children living with drug-abusing (DA) fathers compared to children living in demographically matched homes with alcohol-abusing (AA) or non-substance-abusing fathers. Method: Children's lifetime psychiatric…

  9. Genetic toxicology of abused drugs: a brief review.

    PubMed

    Li, J H; Lin, L F

    1998-11-01

    Although numerous studies have been conducted on abused drugs, most focus on the problems of addiction (dependence) and their neurotoxicities. Now accumulated data have demonstrated that the genotoxicity and/or carcinogenicity of abused drugs can also be detrimental to our health. In this review, commonly abused substances, including LSD, opiates (diacetylmorphine, morphine, opium and codeine), cocaine, cannabis, betel quid and khat, are discussed for their potential genotoxicity/carcinogenicity. The available literature in the field, although not as abundant as for neurotoxicity, clearly indicates the capability of abused drugs to induce genotoxicity.

  10. [Community-based prevention of drug abuse in Japan].

    PubMed

    Shimane, Takuya

    2010-08-01

    The objective of this article is to review community-based drug abuse prevention and relapse prevention in Japan. Japan has a highly efficient system for the primary prevention of drug abuse; this system includes drug abuse education programs in schools and anti-drug abuse campaigns in communities. On the other hand, relapse prevention activities, such as counseling service at mental health welfare centers, self-help groups for drug addicts, and relapse prevention programs at outpatient clinics, are limited because of zero tolerance policies. Therefore, more relapse prevention activities are required in Japanese communities.

  11. Identification and management of prescription drug abuse in pregnancy.

    PubMed

    Worley, Julie

    2014-01-01

    Prescription drug abuse is a growing problem in the United States and many other countries. Estimates of prescription drug abuse rates during pregnancy range from 5% to 20%. The primary prescription drugs designated as controlled drugs with abuse potential in pregnancy are opiates prescribed for pain, benzodiazepines prescribed for anxiety, and stimulants prescribed for attention-deficit/hyperactivity disorder. Prescription drugs are obtained for abuse through diversion methods, such as purchasing them from others or by doctor shopping. The use of prescription drugs puts both the mother and the fetus at high risk during pregnancy. Identification of women who are abusing prescription drugs is important so that treatment can be ensured. It is crucial for healthcare professionals to use a multidisciplinary approach and be supportive and maintain a good rapport with pregnant women who abuse prescription drugs. Management includes inpatient hospitalization for detoxification and withdrawal symptoms, and in the case of opiate abuse, opiate maintenance is recommended for pregnant women for the duration of their pregnancy to reduce relapse rates and improve maternal and fetal outcomes. Other recommendations include referral for support groups and supportive housing.

  12. Elder Abuse and Neglect Content in Higher Education Programs on Aging.

    ERIC Educational Resources Information Center

    Stein, Karen F.

    This study sought to: (1) investigate the degree to which course content on elder abuse and neglect is a part of higher education curriculums in aging; (2) determine which specific elder abuse and neglect course content is included in required and elective coursework; and (3) describe the attitudes of instructors toward including elder abuse and…

  13. New drugs of abuse.

    PubMed

    Rech, Megan A; Donahey, Elisabeth; Cappiello Dziedzic, Jacqueline M; Oh, Laura; Greenhalgh, Elizabeth

    2015-02-01

    Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and have become increasingly popular. Recognition and treatment of new drugs of abuse pose many challenges for health care providers due to lack of quantitative reporting and routine surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal. In this article, we describe the clinical and adverse effects and purported pharmacology of several new classes of drugs of abuse including synthetic cannabinoids, synthetic cathinones, salvia, desomorphine, and kratom. Because many of these substances can have severe or life-threatening adverse effects, knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes (e.g., cholinergic, sympathomimetic, opioid, etc.) are not precipitated by many of these agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases. © 2014 Pharmacotherapy Publications, Inc.

  14. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding.

    PubMed

    Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju; Kaphalia, Bhupendra S; Calhoun, William J

    2014-06-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to <1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. Copyright © 2014 Elsevier Inc

  15. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

    PubMed Central

    Kaphalia, Lata; Boroumand, Nahal; Ju, Hyunsu; Kaphalia, Bhupendra S.; Calhoun, William J.

    2014-01-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to <0.2% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 were observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. PMID:24625836

  16. Integrated bioethanol production to boost low-concentrated cellulosic ethanol without sacrificing ethanol yield.

    PubMed

    Xu, Youjie; Zhang, Meng; Roozeboom, Kraig; Wang, Donghai

    2018-02-01

    Four integrated designs were proposed to boost cellulosic ethanol titer and yield. Results indicated co-fermentation of corn flour with hydrolysate liquor from saccharified corn stover was the best integration scheme and able to boost ethanol titers from 19.9 to 123.2 g/L with biomass loading of 8% and from 36.8 to 130.2 g/L with biomass loadings of 16%, respectively, while meeting the minimal ethanol distillation requirement of 40 g/L and achieving high ethanol yields of above 90%. These results indicated integration of first and second generation ethanol production could significantly accelerate the commercialization of cellulosic biofuel production. Co-fermentation of starchy substrate with hydrolysate liquor from saccharified biomass is able to significantly enhance ethanol concentration to reduce energy cost for distillation without sacrificing ethanol yields. This novel method could be extended to any pretreatment of biomass from low to high pH pretreatment as demonstrated in this study. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Assessing the environmental sustainability of ethanol from integrated biorefineries

    PubMed Central

    Falano, Temitope; Jeswani, Harish K; Azapagic, Adisa

    2014-01-01

    This paper considers the life cycle environmental sustainability of ethanol produced in integrated biorefineries together with chemicals and energy. Four types of second-generation feedstocks are considered: wheat straw, forest residue, poplar, and miscanthus. Seven out of 11 environmental impacts from ethanol are negative, including greenhouse gas (GHG) emissions, when the system is credited for the co-products, indicating environmental savings. Ethanol from poplar is the best and straw the worst option for most impacts. Land use change from forest to miscanthus increases the GHG emissions several-fold. For poplar, the effect is opposite: converting grassland to forest reduces the emissions by three-fold. Compared to fossil and first-generation ethanol, ethanol from integrated biorefineries is more sustainable for most impacts, with the exception of wheat straw. Pure ethanol saves up to 87% of GHG emissions compared to petrol per MJ of fuel. However, for the current 5% ethanol–petrol blends, the savings are much smaller (<3%). Therefore, unless much higher blends become widespread, the contribution of ethanol from integrated biorefineries to the reduction of GHG emissions will be insignificant. Yet, higher ethanol blends would lead to an increase in some impacts, notably terrestrial and freshwater toxicity as well as eutrophication for some feedstocks. PMID:24478110

  18. Family Medicine Curriculum Guide to Substance Abuse.

    ERIC Educational Resources Information Center

    Liepman, Michael R., Ed.; And Others

    This curriculum guide on substance abuse is intended for teachers of family medicine. Comments, learning objectives, teaching hints, and evaluations of knowledge are provided for each area in all chapters. Chapter 1 focuses on the pharmacology of commonly abused drugs including depressants, opioids, stimulants, hallucinogens, inhalants, and…

  19. Cultures of Abuse within Residential Child Care.

    ERIC Educational Resources Information Center

    Parkin, Wendy; Green, Lorraine

    1997-01-01

    Uses interviews with residents and ex-residents, ethnographic techniques, and document analysis to examine sexuality and sexual abuse in residential childcare settings, including how their culture and leadership contribute to abuse and the denial and invisibility of sexuality. Discusses issues around researching sexuality, children, and abusive…

  20. Bruising and Hemophilia: Accident or Child Abuse?

    ERIC Educational Resources Information Center

    Johnson, Charles F.; Coury, Daniel L.

    1988-01-01

    Two case histories illustrate the difficulty in evaluating abuse/neglect in children with bleeding problems such as hemophilia. Discussed are guidelines for diagnosis and prevention of abuse, including: screening techniques, the need for protection from environmental trauma, parental stress, evaluation of parents' disciplinary methods, and the…

  1. Adolescent, but Not Adult, Binge Ethanol Exposure Leads to Persistent Global Reductions of Choline Acetyltransferase Expressing Neurons in Brain

    PubMed Central

    Vetreno, Ryan P.; Broadwater, Margaret; Liu, Wen; Spear, Linda P.; Crews, Fulton T.

    2014-01-01

    During the adolescent transition from childhood to adulthood, notable maturational changes occur in brain neurotransmitter systems. The cholinergic system is composed of several distinct nuclei that exert neuromodulatory control over cognition, arousal, and reward. Binge drinking and alcohol abuse are common during this stage, which might alter the developmental trajectory of this system leading to long-term changes in adult neurobiology. In Experiment 1, adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-day on/2-day off from postnatal day [P] 25 to P55) treatment led to persistent, global reductions of choline acetyltransferase (ChAT) expression. Administration of the Toll-like receptor 4 agonist lipopolysaccharide to young adult rats (P70) produced a reduction in ChAT+IR that mimicked AIE. To determine if the binge ethanol-induced ChAT decline was unique to the adolescent, Experiment 2 examined ChAT+IR in the basal forebrain following adolescent (P28–P48) and adult (P70–P90) binge ethanol exposure. Twenty-five days later, ChAT expression was reduced in adolescent, but not adult, binge ethanol-exposed animals. In Experiment 3, expression of ChAT and vesicular acetylcholine transporter expression was found to be significantly reduced in the alcoholic basal forebrain relative to moderate drinking controls. Together, these data suggest that adolescent binge ethanol decreases adult ChAT expression, possibly through neuroimmune mechanisms, which might impact adult cognition, arousal, or reward sensitivity. PMID:25405505

  2. Adolescent, but not adult, binge ethanol exposure leads to persistent global reductions of choline acetyltransferase expressing neurons in brain.

    PubMed

    Vetreno, Ryan P; Broadwater, Margaret; Liu, Wen; Spear, Linda P; Crews, Fulton T

    2014-01-01

    During the adolescent transition from childhood to adulthood, notable maturational changes occur in brain neurotransmitter systems. The cholinergic system is composed of several distinct nuclei that exert neuromodulatory control over cognition, arousal, and reward. Binge drinking and alcohol abuse are common during this stage, which might alter the developmental trajectory of this system leading to long-term changes in adult neurobiology. In Experiment 1, adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-day on/2-day off from postnatal day [P] 25 to P55) treatment led to persistent, global reductions of choline acetyltransferase (ChAT) expression. Administration of the Toll-like receptor 4 agonist lipopolysaccharide to young adult rats (P70) produced a reduction in ChAT+IR that mimicked AIE. To determine if the binge ethanol-induced ChAT decline was unique to the adolescent, Experiment 2 examined ChAT+IR in the basal forebrain following adolescent (P28-P48) and adult (P70-P90) binge ethanol exposure. Twenty-five days later, ChAT expression was reduced in adolescent, but not adult, binge ethanol-exposed animals. In Experiment 3, expression of ChAT and vesicular acetylcholine transporter expression was found to be significantly reduced in the alcoholic basal forebrain relative to moderate drinking controls. Together, these data suggest that adolescent binge ethanol decreases adult ChAT expression, possibly through neuroimmune mechanisms, which might impact adult cognition, arousal, or reward sensitivity.

  3. Acamprosate {monocalcium bis(3-acetamidopropane-1-sulfonate)} reduces ethanol-drinking behavior in rats and glutamate-induced toxicity in ethanol-exposed primary rat cortical neuronal cultures.

    PubMed

    Oka, Michiko; Hirouchi, Masaaki; Tamura, Masaru; Sugahara, Seishi; Oyama, Tatsuya

    2013-10-15

    Acamprosate, the calcium salt of bis(3-acetamidopropane-1-sulfonate), contributes to the maintenance of abstinence in alcohol-dependent patients, but its mechanism of action in the central nervous system is unclear. Here, we report the effect of acamprosate on ethanol-drinking behavior in standard laboratory Wistar rats, including voluntary ethanol consumption and the ethanol-deprivation effect. After forced ethanol consumption arranged by the provision of only one drinking bottle containing 10% ethanol, the rats were given a choice between two drinking bottles, one containing water and the other containing 10% ethanol. In rats selected for high ethanol preference, repeated oral administration of acamprosate diminished voluntary ethanol drinking. After three months of continuous access to two bottles, rats were deprived of ethanol for three days and then presented with two bottles again. After ethanol deprivation, ethanol preference was increased, and the increase was largely abolished by acamprosate. After exposure of primary neuronal cultures of rat cerebral cortex to ethanol for four days, neurotoxicity, as measured by the extracellular leakage of lactate dehydrogenase (LDH), was induced by incubation with glutamate for 1h followed by incubation in the absence of ethanol for 24h. The N-methyl-D-aspartate receptor blocker 5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine, the metabotropic glutamate receptor subtype 5 antagonist 6-methyl-2-(phenylethynyl)pyridine and the voltage-gated calcium-channel blocker nifedipine all inhibited glutamate-induced LDH leakage from ethanol-exposed neurons. Acamprosate inhibited the glutamate-induced LDH leakage from ethanol-exposed neurons more strongly than that from intact neurons. In conclusion, acamprosate showed effective reduction of drinking behavior in rats and protected ethanol-exposed neurons by multiple blocking of glutamate signaling. © 2013 Elsevier B.V. All rights reserved.

  4. Exploring taboos: comparing male- and female-perpetrated child sexual abuse.

    PubMed

    Peter, Tracey

    2009-07-01

    The objective of this article is to compare male- and female-perpetrated sexual abuse in terms of victim and abuser characteristics, type of abuse, family structure, and worker information. Bivariate tests of significance were performed on the 1998 Canadian Incidence Study of Reported Child Abuse and Neglect, which included 308 male and 37 female abusers. Results show a prevalence rate of 10.7% for female-perpetrated sexual abuse. Girls were more likely to be victimized for both male- and female-perpetrated sexual violence and females tended to abuse younger children. The majority of children came from families with lower socioeconomic status although one in five victims of female-perpetrated sexual abuse came from middle-class homes. Referrals to child welfare agencies were more likely to be made by nonprofessionals when females abused.

  5. Method for producing ethanol and co-products from cellulosic biomass

    DOEpatents

    Nguyen, Quang A

    2013-10-01

    The present invention generally relates to processes for production of ethanol from cellulosic biomass. The present invention also relates to production of various co-products of preparation of ethanol from cellulosic biomass. The present invention further relates to improvements in one or more aspects of preparation of ethanol from cellulosic biomass including, for example, improved methods for cleaning biomass feedstocks, improved acid impregnation, and improved steam treatment, or "steam explosion."

  6. High-throughput detection of ethanol-producing cyanobacteria in a microdroplet platform.

    PubMed

    Abalde-Cela, Sara; Gould, Anna; Liu, Xin; Kazamia, Elena; Smith, Alison G; Abell, Chris

    2015-05-06

    Ethanol production by microorganisms is an important renewable energy source. Most processes involve fermentation of sugars from plant feedstock, but there is increasing interest in direct ethanol production by photosynthetic organisms. To facilitate this, a high-throughput screening technique for the detection of ethanol is required. Here, a method for the quantitative detection of ethanol in a microdroplet-based platform is described that can be used for screening cyanobacterial strains to identify those with the highest ethanol productivity levels. The detection of ethanol by enzymatic assay was optimized both in bulk and in microdroplets. In parallel, the encapsulation of engineered ethanol-producing cyanobacteria in microdroplets and their growth dynamics in microdroplet reservoirs were demonstrated. The combination of modular microdroplet operations including droplet generation for cyanobacteria encapsulation, droplet re-injection and pico-injection, and laser-induced fluorescence, were used to create this new platform to screen genetically engineered strains of cyanobacteria with different levels of ethanol production.

  7. High-throughput detection of ethanol-producing cyanobacteria in a microdroplet platform

    PubMed Central

    Abalde-Cela, Sara; Gould, Anna; Liu, Xin; Kazamia, Elena; Smith, Alison G.; Abell, Chris

    2015-01-01

    Ethanol production by microorganisms is an important renewable energy source. Most processes involve fermentation of sugars from plant feedstock, but there is increasing interest in direct ethanol production by photosynthetic organisms. To facilitate this, a high-throughput screening technique for the detection of ethanol is required. Here, a method for the quantitative detection of ethanol in a microdroplet-based platform is described that can be used for screening cyanobacterial strains to identify those with the highest ethanol productivity levels. The detection of ethanol by enzymatic assay was optimized both in bulk and in microdroplets. In parallel, the encapsulation of engineered ethanol-producing cyanobacteria in microdroplets and their growth dynamics in microdroplet reservoirs were demonstrated. The combination of modular microdroplet operations including droplet generation for cyanobacteria encapsulation, droplet re-injection and pico-injection, and laser-induced fluorescence, were used to create this new platform to screen genetically engineered strains of cyanobacteria with different levels of ethanol production. PMID:25878135

  8. Acute Ethanol Has Biphasic Effects on Short- and Long-Term Memory in Both Foreground and Background Contextual Fear Conditioning in C57BL/6 Mice

    PubMed Central

    Gulick, Danielle; Gould, Thomas J.

    2009-01-01

    Background Ethanol is a frequently abused, addictive drug that impairs cognitive function. Ethanol may disrupt cognitive processes by altering attention, short-term memory, and/ or long-term memory. Interestingly, some research suggests that ethanol may enhance cognitive processes at lower doses. The current research examined the dose-dependent effects of ethanol on contextual and cued fear conditioning. In addition, the present studies assessed the importance of stimulus salience in the effects of ethanol and directly compared the effects of ethanol on short-term and long-term memory. Methods This study employed both foreground and background fear conditioning, which differ in the salience of contextual stimuli, and tested conditioning at 4 hours, 24 hours, and 1 week in order to assess the effects of ethanol on short-term and long-term memory. Foreground conditioning consisted of 2 presentations of a foot shock unconditioned stimulus (US) (2 seconds, 0.57 mA). Background conditioning consisted of 2 auditory conditioned stimulus (30 seconds, 85 dB white noise)–foot shock (US; 2 seconds, 0.57 mA) pairings. Results For both foreground and background conditioning, ethanol enhanced short-term and long-term memory for contextual and cued conditioning at a low dose (0.25 g/kg) and impaired short-term and long-term memory for contextual and cued conditioning at a high dose (1.0 g/kg). Conclusions These results suggest that ethanol has long-lasting, biphasic effects on short-term and long-term memory for contextual and cued conditioning. Furthermore, the effects of ethanol on contextual fear conditioning are independent of the salience of the context. PMID:17760787

  9. Correcting direct effects of ethanol on translation and transcription machinery confers ethanol tolerance in bacteria

    PubMed Central

    Haft, Rembrandt J. F.; Keating, David H.; Schwaegler, Tyler; Schwalbach, Michael S.; Vinokur, Jeffrey; Tremaine, Mary; Peters, Jason M.; Kotlajich, Matthew V.; Pohlmann, Edward L.; Ong, Irene M.; Grass, Jeffrey A.; Kiley, Patricia J.; Landick, Robert

    2014-01-01

    The molecular mechanisms of ethanol toxicity and tolerance in bacteria, although important for biotechnology and bioenergy applications, remain incompletely understood. Genetic studies have identified potential cellular targets for ethanol and have revealed multiple mechanisms of tolerance, but it remains difficult to separate the direct and indirect effects of ethanol. We used adaptive evolution to generate spontaneous ethanol-tolerant strains of Escherichia coli, and then characterized mechanisms of toxicity and resistance using genome-scale DNAseq, RNAseq, and ribosome profiling coupled with specific assays of ribosome and RNA polymerase function. Evolved alleles of metJ, rho, and rpsQ recapitulated most of the observed ethanol tolerance, implicating translation and transcription as key processes affected by ethanol. Ethanol induced miscoding errors during protein synthesis, from which the evolved rpsQ allele protected cells by increasing ribosome accuracy. Ribosome profiling and RNAseq analyses established that ethanol negatively affects transcriptional and translational processivity. Ethanol-stressed cells exhibited ribosomal stalling at internal AUG codons, which may be ameliorated by the adaptive inactivation of the MetJ repressor of methionine biosynthesis genes. Ethanol also caused aberrant intragenic transcription termination for mRNAs with low ribosome density, which was reduced in a strain with the adaptive rho mutation. Furthermore, ethanol inhibited transcript elongation by RNA polymerase in vitro. We propose that ethanol-induced inhibition and uncoupling of mRNA and protein synthesis through direct effects on ribosomes and RNA polymerase conformations are major contributors to ethanol toxicity in E. coli, and that adaptive mutations in metJ, rho, and rpsQ help protect these central dogma processes in the presence of ethanol. PMID:24927582

  10. Intermittent high-dose ethanol exposures increase motivation for operant ethanol self-administration: possible neurochemical mechanism.

    PubMed

    Li, Zhimin; Zharikova, Alevtina; Vaughan, Cheryl H; Bastian, Jaime; Zandy, Shannon; Esperon, Leonardo; Axman, Elyssia; Rowland, Neil E; Peris, Joanna

    2010-01-15

    We investigated the neurochemical mechanism of how high-dose ethanol exposure may increase motivation for ethanol consumption. First, we developed an animal model of increased motivation for ethanol using a progressive ratio (PR) schedule. Sprague-Dawley rats were trained to administer 10% ethanol-containing gelatin or plain gelatin (on alternate weeks) in daily 30-min sessions under different fixed ratio (FR) and PR schedules. During FR schedules, rats self-administered about 1 g/kg ethanol, which was decreased to 0.4+/-0.03 g/kg under PR10. Rats then received four pairs of either 3 g/kg ethanol or saline injections during the weeks when the reinforcer was plain gelatin. During subsequent ethanol gel sessions, breakpoints and ethanol consumption rose 40% in the high-dose ethanol group by the fourth set of injections with no change in plain gel responding. Alterations in amino acids in the ventral striatum (VS) during PR10 responding for 10% ethanol gelatin and plain gelatin were measured using microdialysis sampling coupled with capillary electrophoresis and laser-induced fluorescence detection. There was greater release of taurine, glycine and glutamate in the NAC of the high-dose ethanol rats during 10% ethanol-containing gelatin responding, compared to the control rats or during plain gel responding. An increase in the release of glycine in this same brain region has recently been shown to be involved with anticipation of a reward. Thus, it appears that intermittent high-dose ethanol exposure not only increases motivation for ethanol responding but may also change neurotransmitter release that mediates anticipation of reinforcement, which may play a key role in the development of alcoholism. Copyright 2009 Elsevier B.V. All rights reserved.

  11. Sexual abuses.

    PubMed

    Abel, G G; Rouleau, J L

    1995-03-01

    The sexual abuses described in this article are occurring so frequently that they constitute a public health problem. Superficially they appear to be quite dissimilar because they involve individuals of different ages, different settings, and different power relationships. Basic to each of them, however, is an absence of consent by the victim and the misuse of power by the perpetrator in order to accomplish the abuse. We now have an adequate understanding of each of these abuses and it is now time to make a concerted effort to stop these abuses. This will require the combined efforts of the education of the public, improved identification of the abuses, treatment of the victims, and an appropriate criminal justice response combined with treatment of the perpetrator.

  12. Spouse Abuse, Child Abuse, and Substance Abuse Among Army Facilities: Co-Occurrence, Correlations and Service Delivery Issues

    DTIC Science & Technology

    2006-03-01

    refer spouse abuse or child abuse offenders with identified alcohol or other drug involvement to the on-base counseling center for a substance...abuse assessment. The military’s response to combat substance abuse involves a combination of education, prevention, random testing for illicit drug ...data from three Army sources: the Army Central Registry (ACR), the Drug and Alcohol Management Information System (DAMIS), and Army personnel data

  13. Prescription opioid abuse based on representative postmortem toxicology.

    PubMed

    Häkkinen, Margareeta; Vuori, Erkki; Ojanperä, Ilkka

    2014-12-01

    Opioids are important medications for pain and opioid maintenance treatment. Increasing use and abuse of prescription opioids has, however, caused worldwide concern. Our aim was to estimate the ratio between prescription opioid abuse and total use, based on representative postmortem toxicology. Our material included all the medico-legally examined deaths in Finland during 2010-2011 involving positive findings involving buprenorphine, codeine, fentanyl, methadone, oxycodone, or tramadol. We studied drug abuse by age group, with "abuse" meaning licit opioids used illicitly as narcotics. Drug-abuse history, drug injecting, or laboratory findings of illicit drugs defined an abuser case. We then compared abuser cases and other opioid-related cases between the opioids with the number of fatal poisonings, accidents, suicides, alcohol findings, concomitant opioid use, and median postmortem blood opioid concentrations. Opioid findings numbered 2499 in 2088 cases. Drug abuse involved 545 opioid-positive cases, which in Finland represented 0.5% of those deceased. The proportion of abuser cases among all opioid-related cases for buprenorphine was 85.5%, for methadone 82.4%, for tramadol 29.4%, for codeine 16.3%, for fentanyl 14.5%, and for oxycodone 6.9%. Abuse in age-groups >60 was rare. Concomitant other opioid findings were more frequent in abuser- than in other cases for codeine, oxycodone, and tramadol, whereas alcohol findings were more frequent in buprenorphine, codeine, and fentanyl abuse. Buprenorphine and methadone were most often related to drug abuse. Every other opioid studied involved some abuse, and especially tramadol. Abuse and fatal poisonings were concentrated in men aged 20-49. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. What Do We Know About Ethanol and Alkylates as Pollutants?

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

    Rich, D W; Marchetti, A A; Buscheck, T

    Gov. Davis issued Executive Order D-5-99 in March 1999 calling for removal of methyl tertiary butyl ether (MTBE) from gasoline no later than December 31, 2002. The Executive Order required the California Air Board, State Water Resources Control Board (SWRCB) and Office of Environmental Health Hazard Assessment (OEHHA) to prepare an analysis of potential impacts and health risks that may be associated with the use of ethanol as a fuel oxygenate. The SWRCB contracted with the Lawrence Livermore National Laboratory (LLNL) to lead a team of researchers, including scientists from Clarkson University, University of Iowa, and University of California, Davis,more » in evaluating the potential ground and surface water impacts that may occur if ethanol is used to replace MTBE. These findings are reported in the document entitled Health and Environmental Assessment of the Use of Ethanol as a Fuel Oxygenate. This document has been peer reviewed and presented to the California Environmental Policy Council and may be viewed at: http://www-erd.llnl.gov/ethanol/. Ethanol used for fuels is made primarily from grains, but any feed stock containing sugar, starch, or cellulose can be fermented to ethanol. Ethanol contains 34.7% oxygen by weight. It is less dense than water, but infinitely soluble in water. Ethanol vapors are denser than air. One and a half gallons of ethanol have the same energy as one gallon of gasoline. Pure fuel ethanol, and gasoline with ethanol, conducts electricity, while gasoline without ethanol is an insulator. Corrosion and compatibility of materials is an issue with the storage of pure ethanol and gasoline with high percentages of ethanol, but these issues are less important if gasoline with less than 10% ethanol is used.« less

  15. Paradoxical Neurobehavioral Rescue by Memories of Early-Life Abuse: The Safety Signal Value of Odors Learned during Abusive Attachment

    PubMed Central

    Raineki, Charlis; Sarro, Emma; Rincón-Cortés, Millie; Perry, Rosemarie; Boggs, Joy; Holman, Colin J; Wilson, Donald A; Sullivan, Regina M

    2015-01-01

    Caregiver-associated cues, including those learned in abusive attachment, provide a sense of safety and security to the child. Here, we explore how cues associated with abusive attachment, such as maternal odor, can modify the enduring neurobehavioral effects of early-life abuse. Two early-life abuse models were used: a naturalistic paradigm, where rat pups were reared by an abusive mother; and a more controlled paradigm, where pups underwent peppermint odor-shock conditioning that produces an artificial maternal odor through engagement of the attachment circuit. Animals were tested for maternal odor preference in infancy, forced swim test (FST), social behavior, and sexual motivation in adulthood—in the presence or absence of maternal odors (natural or peppermint). Amygdala odor-evoked local field potentials (LFPs) via wireless electrodes were also examined in response to the maternal odors in adulthood. Both early-life abuse models induced preference for the maternal odors in infancy. In adulthood, these early-life abuse models produced FST deficits and decreased social behavior, but did not change sexual motivation. Presentation of the maternal odors rescued FST and social behavior deficits induced by early-life abuse and enhanced sexual motivation in all animals. In addition, amygdala LFPs from both abuse animal models showed unique activation within the gamma frequency (70–90 Hz) bands in response to the specific maternal odor present during early-life abuse. These results suggest that attachment-related cues learned during infancy have a profound ability to rescue neurobehavioral dysregulation caused by early-life abuse. Paradoxically, abuse-associated cues seem to acquire powerful and enduring antidepressive properties and alter amygdala modulation. PMID:25284320

  16. Paradoxical neurobehavioral rescue by memories of early-life abuse: the safety signal value of odors learned during abusive attachment.

    PubMed

    Raineki, Charlis; Sarro, Emma; Rincón-Cortés, Millie; Perry, Rosemarie; Boggs, Joy; Holman, Colin J; Wilson, Donald A; Sullivan, Regina M

    2015-03-01

    Caregiver-associated cues, including those learned in abusive attachment, provide a sense of safety and security to the child. Here, we explore how cues associated with abusive attachment, such as maternal odor, can modify the enduring neurobehavioral effects of early-life abuse. Two early-life abuse models were used: a naturalistic paradigm, where rat pups were reared by an abusive mother; and a more controlled paradigm, where pups underwent peppermint odor-shock conditioning that produces an artificial maternal odor through engagement of the attachment circuit. Animals were tested for maternal odor preference in infancy, forced swim test (FST), social behavior, and sexual motivation in adulthood-in the presence or absence of maternal odors (natural or peppermint). Amygdala odor-evoked local field potentials (LFPs) via wireless electrodes were also examined in response to the maternal odors in adulthood. Both early-life abuse models induced preference for the maternal odors in infancy. In adulthood, these early-life abuse models produced FST deficits and decreased social behavior, but did not change sexual motivation. Presentation of the maternal odors rescued FST and social behavior deficits induced by early-life abuse and enhanced sexual motivation in all animals. In addition, amygdala LFPs from both abuse animal models showed unique activation within the gamma frequency (70-90 Hz) bands in response to the specific maternal odor present during early-life abuse. These results suggest that attachment-related cues learned during infancy have a profound ability to rescue neurobehavioral dysregulation caused by early-life abuse. Paradoxically, abuse-associated cues seem to acquire powerful and enduring antidepressive properties and alter amygdala modulation.

  17. Involvement of ventral tegmental area ionotropic glutamate receptors in the expression of ethanol-induced conditioned place preference.

    PubMed

    Pina, Melanie M; Cunningham, Christopher L

    2016-10-15

    The ventral tegmental area (VTA) is a well-established neural substrate of reward-related processes. Activity within this structure is increased by the primary and conditioned rewarding effects of abused drugs and its engagement is heavily reliant on excitatory input from structures upstream. In the case of drug seeking, it is thought that exposure to drug-associated cues engages glutamatergic VTA afferents that signal directly to dopamine cells, thereby triggering this behavior. It is unclear, however, whether glutamate input to VTA is directly involved in ethanol-associated cue seeking. Here, the role of intra-VTA ionotropic glutamate receptor (iGluR) signaling in ethanol-cue seeking was evaluated in DBA/2J mice using an ethanol conditioned place preference (CPP) procedure. Intra-VTA iGluRs α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR)/kainate and N-methyl-d-aspartate (NMDAR) were blocked during ethanol CPP expression by co-infusion of antagonist drugs 6,7-dinitroquinoxaline-2,3-dione (DNQX; AMPA/kainate) and d-(-)-2-Amino-5-phosphonopentanoic acid (AP5; NMDA). Compared to aCSF, bilateral infusion of low (1 DNQX+100 AP5ng/side) and high (5 DNQX+500 AP5ng/side) doses of the AMPAR and NMDAR antagonist cocktail into VTA blocked ethanol CPP expression. This effect was site specific, as DNQX/AP5 infusion proximal to VTA did not significantly impact CPP expression. An increase in activity was found at the high but not low dose of DNQX/AP5. These findings demonstrate that activation of iGluRs within the VTA is necessary for ethanol-associated cue seeking, as measured by CPP. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. GABAA Receptor Regulation of Voluntary Ethanol Drinking Requires PKCε

    PubMed Central

    Besheer, Joyce; Lepoutre, Veronique; Mole, Beth; Hodge, Clyde W.

    2010-01-01

    Protein kinase C (PKC) regulates a variety of neural functions, including ion channel activity, neurotransmitter release, receptor desensitization and differentiation. We have shown previously that mice lacking the ε-isoform of PKC (PKCε) self-administer 75% less ethanol and exhibit supersensitivity to acute ethanol and allosteric positive modulators of GABAA receptors when compared with wild-type controls. The purpose of the present study was to examine involvement of PKCε in GABAA receptor regulation of voluntary ethanol drinking. To address this question, PKCε null-mutant and wild-type control mice were allowed to drink ethanol (10% v/v) vs. water on a two-bottle continuous access protocol. The effects of diazepam (nonselective GABAA BZ positive modulator), zolpidem (GABAA α1 agonist), L-655,708 (BZ-sensitive GABAA α5 inverse agonist), and flumazenil (BZ antagonist) were then tested on ethanol drinking. Ethanol intake (grams/kg/day) by wild-type mice decreased significantly after diazepam or zolpidem but increased after L-655,708 administration. Flumazenil antagonized diazepam-induced reductions in ethanol drinking in wild-type mice. However, ethanol intake by PKCε null mice was not altered by any of the GABAergic compounds even though effects were seen on water drinking in these mice. Increased acute sensitivity to ethanol and diazepam, which was previously reported, was confirmed in PKCε null mice. Thus, results of the present study show that PKCε null mice do not respond to doses of GABAA BZ receptor ligands that regulate ethanol drinking by wild-type control mice. This suggests that PKCε may be required for GABAA receptor regulation of chronic ethanol drinking. PMID:16881070

  19. Abuse of Amphetamines and Structural Abnormalities in Brain

    PubMed Central

    Berman, Steven; O’Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D.

    2009-01-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse, and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques that include manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common, and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre-existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain

  20. Methanol toxicity secondary to inhalant abuse in adult men.

    PubMed

    Wallace, Erik A; Green, Adam S

    2009-03-01

    The purpose of this report is to evaluate the presentation, treatment, and outcomes of adults with methanol toxicity from inhalation of carburetor cleaning fluid fumes. Retrospective chart review of adults with positive serum volatile screen for methanol and history of carburetor cleaning fluid fume inhalation. Sixteen patients were admitted 68 times. Eleven Native American patients accounted for 90% of admissions. Sixty-five cases presented with nausea/vomiting; 27 with intoxication or altered mental status; 21 with specific visual complaints. About 93% had a pH <7.35, 96% had serum bicarbonate <20 mEq/L, 81% had osmolal gap >or=10 mOsm/L, and 69% had anion gap >16. Ten had an initial serum methanol level <20 mg/dL, 29 cases 20-49 mg/dL, 19 cases >or=50 mg/dL. Six patients had a measurable serum ethanol level. Of the 29 patients with a methanol level of 20-49 mg/dL, 20 received intravenous antidote (ethanol or fomepizole); three received an antidote and hemodialysis. All who presented with a serum methanol level >or=50 mg/dL received intravenous ethanol or fomepizole. All visual symptoms resolved before discharge and all patients survived without sequelae. Discussion. This is the largest reported number of cases of methanol toxicity from the inhalation of carburetor cleaning fluid fumes and demonstrates a problem with recurrent abuse among some older Native American men. Intentional inhalation of methanol fumes may produce toxicity. Clinicians need to question patients, especially older Native American men, regarding the possible inhalation of carburetor cleaning fluid fumes in those who present with an unexplained metabolic anion gap acidosis.

  1. Effects of Vigabatrin, an Irreversible GABA Transaminase Inhibitor, on Ethanol Reinforcement and Ethanol Discriminative Stimuli in Mice

    PubMed Central

    Griffin, William C.; Nguyen, Shaun A.; Deleon, Christopher P.; Middaugh, Lawrence D.

    2012-01-01

    We tested the hypothesis that the irreversible gamma-amino butyric acid (GABA) transaminase inhibitor, γ-vinyl GABA (Vigabatrin; VGB) would reduce ethanol reinforcement and enhance the discriminative stimulus effect of ethanol, effectively reducing ethanol intake. The present studies used adult C57BL/6J (B6) mice in well-established operant, two-bottle choice consumption, locomotor activity and ethanol discrimination procedures, to examine comprehensively the effects of VGB on ethanol-supported behaviors. VGB dose-dependently reduced operant responding for ethanol as well as ethanol consumption for long periods of time. Importantly, a low dose (200 mg/kg) of VGB was selective for reducing ethanol responding without altering intake of food or water reinforcement. Higher VGB doses (>200 mg/kg) still reduced ethanol intake, but also significantly increased water consumption and, more modestly, increased food consumption. While not affecting locomotor activity on its own, VGB interacted with ethanol to reduce the stimulatory effects of ethanol on locomotion. Finally, VGB (200 mg/kg) significantly enhanced the discriminative stimulus effects of ethanol as evidenced by significant left-ward and up-ward shifts in ethanol generalization curves. Interestingly, VGB treatment was associated with slight increases in blood ethanol concentrations. The reduction in ethanol intake by VGB appears to be related to the ability of VGB to potentiate the pharmacological effects of ethanol. PMID:22336593

  2. Toxicological Outcomes in Rats Exposed to Inhaled Ethanol During Gestation

    EPA Science Inventory

    Recent legislation has encouraged replacing petroleum-based fuels with renewable alternatives including ethanol, which is currently blended with gasoline in the United States at concentrations up to 15%. Efforts to increase the amount of ethanol in gasoline have prompted concerns...

  3. Carrying the pain of abuse: gender-specific findings on the relationship between childhood physical abuse and obesity in adulthood.

    PubMed

    Fuller-Thomson, Esme; Sinclair, Deborah A; Brennenstuhl, Sarah

    2013-01-01

    Childhood abuse has been associated with negative adult health outcomes, including obesity. This study sought to investigate the association between childhood physical abuse and adult obesity, while controlling for five clusters of potentially confounding factors: childhood stressors, socioeconomic indicators, marital status, health behaviors, and mental health. Representative data from the 2005 Canadian Community Health Survey were selected. The response rate was approximately 84%. Gender-specific logistic regression analyses determined the association between abuse and obesity, while controlling for age and race and five clusters of potentially confounding factors. Of the 12,590 respondents with complete data, 2,787 were obese and 976 reported physical abuse as a child or adolescent by someone close to them. Among women with childhood physical abuse compared to no abuse, the odds of obesity were 35% higher, even when controlling for age, race, and the five clusters of factors (odds ratio (OR) = 1.35; 95% confidence interval (CI) = 1.09, 1.67). Childhood physical abuse was not associated with adult obesity among men (OR = 1.12; 95% CI = 0.82, 1.53). This study provides one of the first population-based, gender-specific analyses of the association between childhood physical abuse and obesity controlling for a wide range of factors. The gender-specific findings require further exploration.

  4. [Pharmacist as gatekeeper: combating medication abuse and dependence].

    PubMed

    Shimane, Takuya

    2013-01-01

      The nonmedical use of medications, including psychotropic drugs, is a growing health problem in Japan. According to a nationwide survey of mental hospitals, the proportion of patients with sedative (mainly benzodiazepine)-related disorders has more than doubled over the last decade. An association between psychotropic drug overdose and suicide risk has also been reported. Furthermore, over-the-counter drug abuse is still a serious problem in Japan. In recent years, pharmacists have been expected to act as gatekeepers, making timely identifications of suicide risk or substance abuse and directing these individuals to appropriate medical care facilities. In August 2012, the revised Comprehensive Suicide Measures Act identified pharmacists as one professional group that should act as gatekeepers. This article begins by reviewing the fundamental terms involved in understanding the nonmedical use of medications, including abuse, dependence, and intoxication. The current situation of substance abuse and dependence is then introduced through a summary of several epidemiological surveys conducted in Japan. Finally, the role of pharmacists as gatekeepers in preventing substance abuse and dependence on medications is discussed.

  5. Metabolomic approach for improving ethanol stress tolerance in Saccharomyces cerevisiae.

    PubMed

    Ohta, Erika; Nakayama, Yasumune; Mukai, Yukio; Bamba, Takeshi; Fukusaki, Eiichiro

    2016-04-01

    The budding yeast Saccharomyces cerevisiae is widely used for brewing and ethanol production. The ethanol sensitivity of yeast cells is still a serious problem during ethanol fermentation, and a variety of genetic approaches (e.g., random mutant screening under selective pressure of ethanol) have been developed to improve ethanol tolerance. In this study, we developed a strategy for improving ethanol tolerance of yeast cells based on metabolomics as a high-resolution quantitative phenotypic analysis. We performed gas chromatography-mass spectrometry analysis to identify and quantify 36 compounds on 14 mutant strains including knockout strains for transcription factor and metabolic enzyme genes. A strong relation between metabolome of these mutants and their ethanol tolerance was observed. Data mining of the metabolomic analysis showed that several compounds (such as trehalose, valine, inositol and proline) contributed highly to ethanol tolerance. Our approach successfully detected well-known ethanol stress related metabolites such as trehalose and proline thus, to further prove our strategy, we focused on valine and inositol as the most promising target metabolites in our study. Our results show that simultaneous deletion of LEU4 and LEU9 (leading to accumulation of valine) or INM1 and INM2 (leading to reduction of inositol) significantly enhanced ethanol tolerance. This study shows the potential of the metabolomic approach to identify target genes for strain improvement of S. cerevisiae with higher ethanol tolerance. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  6. Substance abuse as a symptom of childhood sexual abuse.

    PubMed

    Teusch, R

    2001-11-01

    The recovery process of a 37-year-old woman with adult onset posttraumatic stress disorder (PTSD) is presented. The patient had suffered childhood sexual abuse and had self-medicated for many years with drugs and alcohol to maintain the dissociation of memories of abuse and to facilitate interpersonal functioning. Upon onset of PTSD, the patient's substance abuse became a full-blown addiction that was highly resistant to treatment. It became evident that her substance abuse symbolically repeated her traumatization. In reexperiencing the affects associated with her earlier trauma (despair, denial, shame, and helplessness) as part of her substance abuse and in the transference, the patient was able to gain mastery over these affects and, subsequently, was able to achieve a stable recovery from both illnesses.

  7. Oxycodone-induced tolerance to respiratory depression: reversal by ethanol, pregabalin and protein kinase C inhibition.

    PubMed

    Hill, Rob; Dewey, William L; Kelly, Eamonn; Henderson, Graeme

    2018-06-01

    Oxycodone, a prescription opioid, is a major drug of abuse, especially in the USA, and contributes significantly to opioid overdose deaths each year. Overdose deaths result primarily from respiratory depression. We have studied respiratory depression by oxycodone and have characterized how tolerance develops on prolonged exposure to the drug. We have investigated the role of PKC in maintaining tolerance and have examined whether ethanol or pregabalin reverses oxycodone-induced tolerance. Respiration was measured in male CD-1 mice by whole-body plethysmography. Mice were preinjected with oxycodone then implanted with mini-pumps (s.c.) delivering 20, 45 or 120 mg·kg -1 ·day -1 oxycodone for 6 days and subsequently challenged with oxycodone (3 mg·kg -1 , i.p.) or morphine (10 mg·kg -1 , i.p.) to assess the level of tolerance. Oxycodone-treated mice developed tolerance to oxycodone and cross tolerance to morphine-induced respiratory depression. Tolerance was less with 20 mg·kg -1 ·day -1 than with 45 or 120 mg·kg -1 ·day -1 oxycodone treatment. At doses that do not depress respiration, ethanol (0.3 g·kg -1 ), pregabalin (20 mg·kg -1 ) and calphostin C (45 μg·kg -1 ) all reversed oxycodone-induced tolerance resulting in significant respiratory depression. Reversal of tolerance was less in mice treated with oxycodone (120 mg·kg -1 ·day -1 ). In mice receiving ethanol and calphostin C or ethanol and pregabalin, there was no greater reversal of tolerance than seen with either drug alone. These data suggest that oxycodone-induced tolerance is mediated by PKC and that reversal of tolerance by ethanol or pregabalin may be a contributory factor in oxycodone overdose deaths. © 2018 The British Pharmacological Society.

  8. Other Drugs of Abuse

    MedlinePlus

    ... People Abuse » Other Drugs of Abuse Other Drugs of Abuse Listen There are many other drugs of abuse, ... and Rehab Resources About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  9. Self-Esteem and Attitudes toward Love in Abused and Non-Abused Women.

    ERIC Educational Resources Information Center

    Chambliss, Catherine; And Others

    This study sought to identify personality differences in abused versus non-abused women. Abused women (N=25) were from several centers for abused women and non-abused women (N=39) were students in evening psychology classes. All subjects completed Rubin's Love Scale, the abbreviated Dominance and Romanticism Scale, Rosenberg's Self-Esteem Scale,…

  10. Adolescent rats are resistant to the development of ethanol-induced chronic tolerance and ethanol-induced conditioned aversion.

    PubMed

    Pautassi, Ricardo Marcos; Godoy, Juan Carlos; Molina, Juan Carlos

    2015-11-01

    The analysis of chronic tolerance to ethanol in adult and adolescent rats has yielded mixed results. Tolerance to some effects of ethanol has been reported in adolescents, yet other studies found adults to exhibit greater tolerance than adolescents or comparable expression of the phenomena at both ages. Another unanswered question is how chronic ethanol exposure affects subsequent ethanol-mediated motivational learning at these ages. The present study examined the development of chronic tolerance to ethanol's hypothermic and motor stimulating effects, and subsequent acquisition of ethanol-mediated odor conditioning, in adolescent and adult male Wistar rats given every-other-day intragastric administrations of ethanol. Adolescent and adult rats exhibited lack of tolerance to the hypothermic effects of ethanol during an induction phase; whereas adults, but not adolescents, exhibited a trend towards a reduction in hypothermia at a challenge phase (Experiment 1). Adolescents, unlike adults, exhibited ethanol-induced motor activation after the first ethanol administration. Adults, but not adolescents, exhibited conditioned odor aversion by ethanol. Subsequent experiments conducted only in adolescents (Experiment 2, Experiment 3 and Experiment 4) manipulated the context, length and predictability of ethanol administration. These manipulations did not promote the expression of ethanol-induced tolerance. This study indicated that, when moderate ethanol doses are given every-other day for a relatively short period, adolescents are less likely than adults to develop chronic tolerance to ethanol-induced hypothermia. This resistance to tolerance development could limit long-term maintenance of ethanol intake. Adolescents, however, exhibited greater sensitivity than adults to the acute motor stimulating effects of ethanol and a blunted response to the aversive effects of ethanol. This pattern of response may put adolescents at risk for early initiation of ethanol intake

  11. Chronic Ethanol Intake Alters Circadian Phase Shifting and Free-Running Period in Mice

    PubMed Central

    Seggio, Joseph A.; Fixaris, Michael C.; Reed, Jeffrey D.; Logan, Ryan W.; Rosenwasser, Alan M.

    2011-01-01

    Chronic alcohol intake is associated with widespread disruptions in sleep and circadian rhythms in both human alcoholics and in experimental animals. Recent studies have demonstrated that chronic and acute ethanol treatments alter fundamental properties of the circadian pacemaker—including free-running period and responsiveness to photic and nonphotic phase-shifting stimuli—in rats and hamsters. In the present work, the authors extend these observations to the C57BL/6J mouse, an inbred strain characterized by very high levels of voluntary ethanol intake and by reliable and stable free-running circadian activity rhythms. Mice were housed individually in running-wheel cages under conditions of either voluntary or forced ethanol intake, whereas controls were maintained on plain water. Forced ethanol intake significantly attenuated photic phase delays (but not phase advances) and shortened free-running period in constant darkness, but voluntary ethanol intake failed to affect either of these parameters. Thus, high levels of chronic ethanol intake, beyond those normally achieved under voluntary drinking conditions, are required to alter fundamental circadian pacemaker properties in C57BL/6J mice. These observations may be related to the relative ethanol insensitivity displayed by this strain in several other phenotypic domains, including ethanol-induced sedation, ataxia, and withdrawal. Additional experiments will investigate chronobiological sensitivity to ethanol in a range of inbred strains showing diverse ethanol-related phenotypes. PMID:19625732

  12. Chronic ethanol intake alters circadian phase shifting and free-running period in mice.

    PubMed

    Seggio, Joseph A; Fixaris, Michael C; Reed, Jeffrey D; Logan, Ryan W; Rosenwasser, Alan M

    2009-08-01

    Chronic alcohol intake is associated with widespread disruptions in sleep and circadian rhythms in both human alcoholics and in experimental animals. Recent studies have demonstrated that chronic and acute ethanol treatments alter fundamental properties of the circadian pacemaker--including free-running period and responsiveness to photic and nonphotic phase-shifting stimuli--in rats and hamsters. In the present work, the authors extend these observations to the C57BL/6J mouse, an inbred strain characterized by very high levels of voluntary ethanol intake and by reliable and stable free-running circadian activity rhythms. Mice were housed individually in running-wheel cages under conditions of either voluntary or forced ethanol intake, whereas controls were maintained on plain water. Forced ethanol intake significantly attenuated photic phase delays (but not phase advances) and shortened free-running period in constant darkness, but voluntary ethanol intake failed to affect either of these parameters. Thus, high levels of chronic ethanol intake, beyond those normally achieved under voluntary drinking conditions, are required to alter fundamental circadian pacemaker properties in C57BL/6J mice. These observations may be related to the relative ethanol insensitivity displayed by this strain in several other phenotypic domains, including ethanol-induced sedation, ataxia, and withdrawal. Additional experiments will investigate chronobiological sensitivity to ethanol in a range of inbred strains showing diverse ethanol-related phenotypes.

  13. Prenatal Ethanol Increases Sucrose Reinforcement, an Effect Strengthened by Postnatal Association of Ethanol and Sucrose

    PubMed Central

    Culleré, Marcela Elena; Spear, Norman E.; Molina, Juan Carlos

    2014-01-01

    Late prenatal exposure to ethanol recruits sensory processing of the drug and of its motivational properties, an experience that leads to heightened ethanol affinity. Recent studies indicate common sensory and neurobiological substrates between this drug and sweet tastants. Using a recently developed operant conditioning technique for infant rats, we examined the effects of prenatal ethanol history upon sucrose self-administration (postnatal days, PDs 14–17). Prior to the last conditioning session, a low (0.5 g/kg) or a high (2.5 g/kg) ethanol dose were paired with sucrose. The intention was to determine if ethanol would inflate or devalue the reinforcing capability of the tastant and if these effects are dependent upon prenatal ethanol history. Male and female pups prenatally exposed to ethanol (2.0 g/kg) responded more when reinforced with sucrose than pups lacking this antenatal experience. Independently of prenatal status, a low ethanol dose (0.5 g/kg) enhanced the reinforcing capability of sucrose while the highest dose (2.5 g/kg) seemed to ameliorate the motivational properties of the tastant. During extinction (PD 18), two factors were critical in determining persistence of responding despite reinforcement omission. Pups prenatally exposed to ethanol that subsequently experienced the low ethanol dose paired with sucrose, showed higher resistance to extinction. The effects here reported were not associated with differential blood alcohol levels across prenatal treatments. These results indicate that fetal ethanol experience promotes affinity for a natural sweet reinforcer and that low doses of ethanol are also capable of enhancing the positive motivational consequences of sucrose when ethanol and sucrose are paired during infancy. PMID:24398347

  14. Factors Associated with Sexual Behavior Problems in Young Sexually Abused Children.

    ERIC Educational Resources Information Center

    Hall, Darlene Kordich; Mathews, Fred; Pearce, John

    1998-01-01

    Analysis of data from the clinical records of 100 sexually abused boys and girls, ages 3-7 years, identified five variables predictive of sexual behavior problems, including sexual arousal of the child during the abuse, perpetrator's use of sadism, a history of physical and emotional abuse, and who the child blames for the abuse. (DB)

  15. Emergency department length of stay for ethanol intoxication encounters.

    PubMed

    Klein, Lauren R; Driver, Brian E; Miner, James R; Martel, Marc L; Cole, Jon B

    2017-12-08

    Emergency Department (ED) encounters for ethanol intoxication are becoming increasingly common. The purpose of this study was to explore factors associated with ED length of stay (LOS) for ethanol intoxication encounters. This was a multi-center, retrospective, observational study of patients presenting to the ED for ethanol intoxication. Data were abstracted from the electronic medical record. To explore factors associated with ED LOS, we created a mixed-effects generalized linear model. We identified 18,664 eligible patients from 6 different EDs during the study period (2012-2016). The median age was 37years, 69% were male, and the median ethanol concentration was 213mg/dL. Median LOS was 348min (range 43-1658). Using a mixed-effects generalized linear model, independent variables associated with a significant increase in ED LOS included use of parenteral sedation (beta=0.30, increase in LOS=34%), laboratory testing (beta=0.21, increase in LOS=23%), as well as the hour of arrival to the ED, such that patients arriving to the ED during evening hours (between 18:00 and midnight) had up to an 86% increase in LOS. Variables not significantly associated with an increase in LOS included age, gender, ethanol concentration, psychiatric disposition, using the ED frequently for ethanol intoxication, CT use, and daily ED volume. Variables such as diagnostic testing, treatments, and hour of arrival may influence ED LOS in patients with acute ethanol intoxication. Identification and further exploration of these factors may assist in developing hospital and community based improvements to modify LOS in this population. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Rickets or abuse? A histologic comparison of rickets and child abuse-related fractures.

    PubMed

    Kepron, Charis; Pollanen, Michael S

    2015-03-01

    The bone changes of vitamin D deficiency rickets have been invoked as an alternate explanation for child-abuse related fractures identified through medical imaging. The lack of modern histopathologic comparisons between these two entities limits the abilities of the forensic pathologist to address this differential diagnosis, both in their autopsy reports and on the witness stand. We report a comparison of the histologic appearance of the bones in a two year old child with vitamin D deficiency rickets with fractures occurring in three young children with child abuse. In the case of rickets, there was marked architectural disorganization of endochondral ossification at the costochondral junctions and growth plates of long bones. The child abuse-related fractures showed osteochondral callus at different stages of healing, either centered on a discrete fracture line or at metaphyses (e.g. classical metaphyseal lesions). In many instances, the healing fractures disrupted the line of endochondral ossification. In none of the child abuse-related fractures was there any similarity to the histologic appearance of rickets. The maturation disturbance in the growth plate that occurs in rickets is a distinctive entity that cannot be confused histologically with healing fractures, including the classical metaphyseal lesion.

  17. Observation of Trans-Ethanol and Gauche-Ethanol Complexes with Benzene Using Matrix Isolation Infrared Spectroscopy

    NASA Astrophysics Data System (ADS)

    Amicangelo, Jay; Silbaugh, Matthew J.

    2016-06-01

    Ethanol can exist in two conformers, one in which the OH group is trans to the methyl group (trans-ethanol) and the other in which the OH group is gauche to the methyl group (gauche-ethanol). Matrix isolation infrared spectra of ethanol deposited in 20 K argon matrices display distinct infrared peaks that can be assigned to the trans-ethanol and gauche-ethanol conformers, particularly with the O-H stretching vibrations. Given this, matrix isolation experiments were performed in which ethanol (C_2H_5OH) and benzene (C_6H_6) were co-deposited in argon matrices at 20 K in order to determine if conformer specific ethanol complexes with benzene could be observed in the infrared spectra. New infrared peaks that can be attributed to the trans-ethanol and gauche-ethanol complexes with benzene have been observed near the O-H stretching vibrations of ethanol. The initial identification of the new infrared peaks as being due to the ethanol-benzene complexes was established by performing a concentration study (1:200 to 1:1600 S/M ratios), by comparing the co-deposition spectra with the spectra of the individual monomers, by matrix annealing experiments (35 K), and by performing experiments using isotopically labeled ethanol (C_2D_5OD) and benzene (C_6D_6). Quantum chemical calculations were also performed for the C_2H_5OH-C_6H_6 complexes using density functional theory (B3LYP) and ab initio (MP2) methods. Stable minima were found for the both the trans-ethanol and gauche-ethanol complexes with benzene at both levels of theory and were predicted to have similar interaction energies. Both complexes can be characterized as H-π complexes, in which the ethanol is above the benzene ring with the hydroxyl hydrogen interacting with the π cloud of the ring. The theoretical O-H stretching frequencies for the complexes were predicted to be shifted from the monomer frequencies and from each other and these results were used to make the conformer specific infrared peak assignments

  18. Acute Ethanol Causes Hepatic Mitochondrial Depolarization in Mice: Role of Ethanol Metabolism

    PubMed Central

    Zhong, Zhi; Ramshesh, Venkat K.; Rehman, Hasibur; Liu, Qinlong; Theruvath, Tom P.; Krishnasamy, Yasodha; Lemasters, John J.

    2014-01-01

    Background/Aims An increase of ethanol metabolism and hepatic mitochondrial respiration occurs in vivo after a single binge of alcohol. Here, our aim was to determine how ethanol intake affects hepatic mitochondrial polarization status in vivo in relation to ethanol metabolism and steatosis. Methods Hepatic mitochondrial polarization, permeability transition (MPT), and reduce pyridine nucleotides, and steatosis in mice were monitored by intravital confocal/multiphoton microscopy of the fluorescence of rhodamine 123 (Rh123), calcein, NAD(P)H, and BODIPY493/503, respectively, after gavage with ethanol (1–6 g/kg). Results Mitochondria depolarized in an all-or-nothing fashion in individual hepatocytes as early as 1 h after alcohol. Depolarization was dose- and time-dependent, peaked after 6 to 12 h and maximally affected 94% of hepatocytes. This mitochondrial depolarization was not due to onset of the MPT. After 24 h, mitochondria of most hepatocytes recovered normal polarization and were indistinguishable from untreated after 7 days. Cell death monitored by propidium iodide staining, histology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was low throughout. After alcohol, mitochondrial NAD(P)H autofluorescence increased and decreased, respectively, in hepatocytes with polarized and depolarized mitochondria. Ethanol also caused steatosis mainly in hepatocytes with depolarized mitochondria. Depolarization was linked to ethanol metabolism, since deficiency of alcohol dehydrogenase and cytochrome-P450 2E1 (CYP2E1), the major ethanol-metabolizing enzymes, decreased mitochondrial depolarization by ∼70% and ∼20%, respectively. Activation of aldehyde dehydrogenase decreased depolarization, whereas inhibition of aldehyde dehydrogenase enhanced depolarization. Activation of aldehyde dehydrogenase also markedly decreased steatosis. Conclusions Acute ethanol causes reversible hepatic mitochondrial depolarization in vivo that may contribute to

  19. Sexual Identity Group Differences in Child Abuse and Neglect

    PubMed Central

    Alvy, Lisa M.; Hughes, Tonda L.; Kristjanson, Arlinda F.; Wilsnack, Sharon C.

    2013-01-01

    Research suggests that sexual minority women are more likely than heterosexual women to report childhood abuse, but little is known about potential within-group variations in experiences of abuse among sexual minority women. We investigated rates and characteristics of childhood sexual and physical abuse among women from five sexual identity groups. Our analyses used a pooled sample of women from a national probability study and a large community-based study of sexual minority women designed to replicate the national study’s methodology (pooled n = 953). As predicted, heterosexual women reported significantly less childhood abuse than did women who identified as mostly heterosexual, bisexual, mostly lesbian, or lesbian. There was also considerable variability in abuse rates and characteristics, including severity of abuse, among sexual minority subgroups. To the extent that differences in reports reflect the actual prevalence and severity of abuse experiences, sexual identity subgroup differences in childhood abuse have important clinical and public health implications. PMID:23345571

  20. Autoshaping induces ethanol drinking in nondeprived rats: evidence of long-term retention but no induction of ethanol preference.

    PubMed

    Tomie, Arthur; Kuo, Teresa; Apor, Khristine R; Salomon, Kimberly E; Pohorecky, Larissa A

    2004-04-01

    The effects of autoshaping procedures (paired vs. random) and sipper fluid (ethanol vs. water) on sipper-directed drinking were evaluated in male Long-Evans rats maintained with free access to food and water. For the paired/ethanol group (n=16), autoshaping procedures consisted of presenting the ethanol sipper (containing 0% to 28% unsweetened ethanol) conditioned stimulus (CS) followed by the response-independent presentation of food unconditioned stimulus (US). The random/ethanol group (n=8) received the sipper CS and food US randomly with respect to one another. The paired/water group (n=8) received only water in the sipper CS. The paired/ethanol group showed higher grams per kilogram ethanol intake than the random/ethanol group did at ethanol concentrations of 8% to 28%. The paired/ethanol group showed higher sipper CS-directed milliliter fluid consumption than the paired/water group did at ethanol concentrations of 1% to 6%, and 15%, 16%, 18%, and 20%. Following a 42-day retention interval, the paired/ethanol group showed superior retention of CS-directed drinking of 18% ethanol, relative to the random/ethanol group, and superior retention of CS-directed milliliter fluid drinking relative to the paired/water group. When tested for home cage ethanol preference using limited access two-bottle (28% ethanol vs. water) procedures, the paired/ethanol and random/ethanol groups did not differ on any drinking measures.

  1. Corneal anesthetic abuse and Candida keratitis.

    PubMed

    Chern, K C; Meisler, D M; Wilhelmus, K R; Jones, D B; Stern, G A; Lowder, C Y

    1996-01-01

    Topical corneal anesthetic abuse is a self-inflicted injury, causing profound corneal morbidity. Superimposed infection is an important complicating factor. The authors report four patients with confirmed topical anesthetic abuse of the cornea, in whom Candida keratitis developed. A retrospective review of the medical records of four patients with confirmed topical corneal anesthetic abuse and fungal keratitis. A 21-year-old woman, two 28-year-old women, and a 35-year-old man were included in the study. All these patients sustained a corneal injury, prompting the chronic use of topical anesthetics (0.5% proparacaine hydrochloride in 3 patients, and 0.5% tetracaine hydrochloride and 0.4% benoxinate hydrochloride in the other). Corneal findings included epithelial defects in all patients, focal infiltrate in one patient, and ring-shaped stromal infiltrate in three patients. Topical anesthetic was discontinued, all patients initially were treated empirically with antibacterial agents, and three patients received topical corticosteroids. Subsequent corneal cultures grew Candida spp, Candida albicans specifically in three patients, and local and systemic antifungal therapy was started. Corneas in two patients re-epithelialized; a conjunctival flap was performed on another patient with a descemetocele; and the remaining patient was lost to follow-up, although repeat fungal cultures yielded no growth. Corneal superinfection with Candida may occur during topical anesthetic abuse. Therapy includes discontinuation of the anesthetic and institution of antifungal therapy.

  2. Water-induced ethanol dewetting transition.

    PubMed

    Ren, Xiuping; Zhou, Bo; Wang, Chunlei

    2012-07-14

    The dewetting transitions of two hydrophobic plates immersed in pure water, aqueous ethanol solutions with concentrations from 25% to 90%, and pure ethanol were investigated by molecular dynamics simulations, where the dewetting transition was analogous to a first-order phase transition from liquid to vapor. It was found that the dewetting transitions occurred except that in the pure ethanol system. Although the ethanol molecules prefer to locate in the vicinity of the two plates, the inter-plate region is unfavorable for water molecules, due to losing more than one hydrogen bond. Moreover, each inter-plate water molecule forms hydrogen bonds on average with about two ethanol molecules. These intermolecular hydrogen bonds cause water and ethanol to cooperatively fill or exit the inter-plate region. Thus, water molecules play a more important role in the inter-plate filling/empty process, and induce the ethanol dewetting transition. Our results provide insight into the effect of water on the ethanol dewetting phenomena.

  3. Exploring family environment characteristics and multiple abuse experiences among homeless youth.

    PubMed

    Ferguson, Kristin M

    2009-11-01

    This qualitative study used data from the Social Enterprise Intervention (SEI) pilot study, a comprehensive vocational training program with integrated clinical services for homeless youth. In-depth interviews were conducted with 28 homeless youth participating in the SEI study to explore their perceptions of family environment characteristics and abuse experiences. The constant comparative method was used to analyze transcripts from in-depth interviews with the youth participants. Emergent themes related to family characteristics include home instability, abandonment, and caregiver substance abuse. Abuse-related subthemes include intrafamilial abuse, caregiver abuse, rejection, and deprecation by caregivers. Grounded theory is used to interpret findings and develop working hypotheses to guide future studies of multitype maltreatment among homeless youth.

  4. 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.

  5. Biochemical Disincentives to Fertilizing Cellulosic Ethanol Crops

    NASA Astrophysics Data System (ADS)

    Gallagher, M. E.; Hockaday, W. C.; Snapp, S.; McSwiney, C.; Baldock, J.

    2010-12-01

    Corn grain biofuel crops produce the highest yields when the cropping ecosystem is not nitrogen (N)-limited, achieved by application of fertilizer. There are environmental consequences for excessive fertilizer application to crops, including greenhouse gas emissions, hypoxic “dead zones,” and health problems from N runoff into groundwater. The increase in corn acreage in response to demand for alternative fuels (i.e. ethanol) could exacerbate these problems, and divert food supplies to fuel production. A potential substitute for grain ethanol that could reduce some of these impacts is cellulosic ethanol. Cellulosic ethanol feedstocks include grasses (switchgrass), hardwoods, and crop residues (e.g. corn stover, wheat straw). It has been assumed that these feedstocks will require similar N fertilization rates to grain biofuel crops to maximize yields, but carbohydrate yield versus N application has not previously been monitored. We report the biochemical stocks (carbohydrate, protein, and lignin in Mg ha-1) of a corn ecosystem grown under varying N levels. We measured biochemical yield in Mg ha-1 within the grain, leaf and stem, and reproductive parts of corn plants grown at seven N fertilization rates (0-202 kg N ha-1), to evaluate the quantity and quality of these feedstocks across a N fertilization gradient. The N fertilization rate study was performed at the Kellogg Biological Station-Long Term Ecological Research Site (KBS-LTER) in Michigan. Biochemical stocks were measured using 13C nuclear magnetic resonance spectroscopy (NMR), combined with a molecular mixing model (Baldock et al. 2004). Carbohydrate and lignin are the main biochemicals of interest in ethanol production since carbohydrate is the ethanol feedstock, and lignin hinders the carbohydrate to ethanol conversion process. We show that corn residue carbohydrate yields respond only weakly to N fertilization compared to grain. Grain carbohydrate yields plateau in response to fertilization at

  6. Analysis of fractionation in corn-to-ethanol plants

    NASA Astrophysics Data System (ADS)

    Nelson, Camille

    As the dry grind ethanol industry has grown, the research and technology surrounding ethanol production and co-product value has increased. Including use of back-end oil extraction and front-end fractionation. Front-end fractionation is pre-fermentation separation of the corn kernel into 3 fractions: endosperm, bran, and germ. The endosperm fraction enters the existing ethanol plant, and a high protein DDGS product remains after fermentation. High value oil is extracted out of the germ fraction. This leaves corn germ meal and bran as co-products from the other two streams. These 3 co-products have a very different composition than traditional corn DDGS. Installing this technology allows ethanol plants to increase profitability by tapping into more diverse markets, and ultimately could allow for an increase in profitability. An ethanol plant model was developed to evaluate both back-end oil extraction and front-end fractionation technology and predict the change in co-products based on technology installed. The model runs in Microsoft Excel and requires inputs of whole corn composition (proximate analysis), amino acid content, and weight to predict the co-product quantity and quality. User inputs include saccharification and fermentation efficiencies, plant capacity, and plant process specifications including front-end fractionation and backend oil extraction, if applicable. This model provides plants a way to assess and monitor variability in co-product composition due to the variation in whole corn composition. Additionally the co-products predicted in this model are entered into the US Pork Center of Excellence, National Swine Nutrition Guide feed formulation software. This allows the plant user and animal nutritionists to evaluate the value of new co-products in existing animal diets.

  7. The intergenerational transfer of mother-daughter risk for gender-based abuse.

    PubMed

    McCloskey, Laura Ann

    2013-01-01

    In this 10-year longitudinal study 150 mother-daughter pairs were recruited to participate in a study examining gender-based abuse across three generations. Forms of gender-based abuse included: child sexual abuse, witnessing intimate partner violence against their mothers, and intimate partner violence or dating violence in adolescence or adulthood. Daughters were interviewed when they were on average 9, 14, and 16 years old. Regression analyses revealed that if the grandmother (G1) was abused by her husband, her daughter (G2) was more likely to be sexually molested in childhood and was also more likely to be in an abusive relationship as an adult. If the mother (G2) was sexually abused as a child her daughter (G3) was at increased risk for child sexual abuse. In turn, child sexual abuse for the daughters related to their reports of dating violence in adolescence. Daughters (G3) who were sexually abused expressed more anxiety about romantic relationships, reflecting early attachment conflicts. Both child sexual abuse and anxious romantic attachment style independently predicted adolescent sexual risk-taking as in having multiple sexual partners or dating older men. These findings demonstrate how informative it is to include multiple forms of gender-based abuse in research and practice to better illuminate complex family dynamics. In addition, the findings support previous empirical work showing the importance of attachment behavior in women who are in abusive relationships, which has unique clinical implications.

  8. Ethanol Pharmacokinetics in Neonates and Infants

    PubMed Central

    Marek, Elizabeth; Kraft, Walter K.

    2014-01-01

    Introduction Ethanol has been used for years in neonatal and infant liquid medications, yet the pharmacokinetics, pharmacodynamics, and safety of ethanol in this vulnerable population have not been well characterized. The purpose of this review is to raise awareness of ethanol use as an excipient in neonatal and infant medications and to provide insight, based on the available evidence, into clearance rates of ethanol in babies. We also discuss ethanol pharmacokinetics in adults, theoretical pharmacokinetic changes in neonates and infants as it may apply to ethanol disposition, and case reports involving ethanol exposure in neonates and infants. Materials and methods This study was a narrative review in which relevant papers were selected using databases and scientific search engines such as PubMed with the key words ethanol, infant, and newborninfant. Results It remains unclear what ethanol exposure is safe for neonates and infants. The Food and Drug Administration and American Academy of Pediatrics have both taken action, by either setting limits of ethanol content in over-the-counter medications or by recommending restricted exposure to ethanol-containing pediatric formulations. Conclusions Until the short- and long-term health effects of chronic ethanol administration can be further characterized, ethanol-containing medications should be used with caution. PMID:25379066

  9. Adolescent substance use and abuse: recognition and management.

    PubMed

    Griswold, Kim S; Aronoff, Helen; Kernan, Joan B; Kahn, Linda S

    2008-02-01

    Substance abuse in adolescents is undertreated in the United States. Family physicians are well positioned to recognize substance use in their patients and to take steps to address the issue before use escalates. Comorbid mental disorders among adolescents with substance abuse include depression, anxiety, conduct disorder, and attention-deficit/ hyperactivity disorder. Office-, home-, and school-based drug testing is not routinely recommended. Screening tools for adolescent substance abuse include the CRAFFT questionnaire. Family therapy is crucial in the management of adolescent substance use disorders. Although family physicians may be able to treat adolescents with substance use disorders in the office setting, it is often necessary and prudent to refer patients to one or more appropriate consultants who specialize specifically in substance use disorders, psychology, or psychiatry. Treatment options include anticipatory guidance, brief therapeutic counseling, school-based drug-counseling programs, outpatient substance abuse clinics, day treatment programs, and inpatient and residential programs. Working within community and family contexts, family physicians can activate and oversee the system of professionals and treatment components necessary for optimal management of substance misuse in adolescents.

  10. Gestational Exposure to Inhaled Vapors of Ethanol and Gasoline-Ethanol Blends in Rats

    EPA Science Inventory

    The US automotive fleet is powered primarily by gasoline-ethanol fuel blends containing up to 10% ethanol (ElO). Uncertainties regarding the health risks associated with exposure to ElO prompted assessment of the effects of prenatal exposure to inhaled vapors of gasoline-ethanol ...

  11. Maximizing cellulosic ethanol potentials by minimizing wastewater generation and energy consumption: Competing with corn ethanol.

    PubMed

    Liu, Gang; Bao, Jie

    2017-12-01

    Energy consumption and wastewater generation in cellulosic ethanol production are among the determinant factors on overall cost and technology penetration into fuel ethanol industry. This study analyzed the energy consumption and wastewater generation by the new biorefining process technology, dry acid pretreatment and biodetoxification (DryPB), as well as by the current mainstream technologies. DryPB minimizes the steam consumption to 8.63GJ and wastewater generation to 7.71tons in the core steps of biorefining process for production of one metric ton of ethanol, close to 7.83GJ and 8.33tons in corn ethanol production, respectively. The relatively higher electricity consumption is compensated by large electricity surplus from lignin residue combustion. The minimum ethanol selling price (MESP) by DryPB is below $2/gal and falls into the range of corn ethanol production cost. The work indicates that the technical and economical gap between cellulosic ethanol and corn ethanol has been almost filled up. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Disrespect, harassment, and abuse

    PubMed Central

    Miedema, Baukje; Easley, Julie; Fortin, Pierrette; Hamilton, Ryan; Tatemichi, Sue

    2009-01-01

    ABSTRACT OBJECTIVE To examine harassment and abusive encounters between family physicians and their patients or colleagues in the workplace. DESIGN Qualitative case study using semistructured interviews. SETTING Province of New Brunswick. PARTICIPANTS Forty-eight family physicians from across the province. METHODS A collective case-study approach was developed, with 24 cases of 2 individuals per case. Cases were selected based on sex, location (urban or rural), language (French or English), and number of years since medical school graduation (< 10 years, 10 to 20 years, or > 20 years). Physicians were interviewed in either French or English. Participants were recruited using the College of Physicians and Surgeons of New Brunswick’s physician directory. Based on the rates of response and participation, some cases were overrepresented, while others were not completed. All interviews were audiotaped, transcribed verbatim, and analyzed thematically using a categorical aggregation approach. A coding scheme for the thematic analysis was developed by the research team before the interviews were transcribed. MAIN FINDINGS Although the original intent of this study was to examine the work environment of family physicians in light of the increasing number of women entering the profession, harassment and abusive encounters in the workplace emerged as a main theme. These encounters ranged from minor to severe. Minor abusive encounters included disrespectful behaviour and verbal threats by patients, their families, and occasionally colleagues. More severe forms of harassment involved physical threats, physical encounters, and stalking. Demanding patients, such as heavy drug users, were often seen as threatening. Location of practice, years in practice, and sex of the physician seemed to affect abusive encounters—young, female, rural physicians appeared to experience such encounters most often. CONCLUSION Abusive encounters in the workplace are concerning. It is essential to

  13. Norepinephrine transporter: a candidate gene for initial ethanol sensitivity in inbred long-sleep and short-sleep mice.

    PubMed

    Haughey, Heather M; Kaiser, Alan L; Johnson, Thomas E; Bennett, Beth; Sikela, James M; Zahniser, Nancy R

    2005-10-01

    Altered noradrenergic neurotransmission is associated with depression and may contribute to drug abuse and alcoholism. Differential initial sensitivity to ethanol is an important predictor of risk for future alcoholism, making the inbred long-sleep (ILS) and inbred short-sleep (ISS) mice a useful model for identifying genes that may contribute to alcoholism. In this study, molecular biological, neurochemical, and behavioral approaches were used to test the hypothesis that the norepinephrine transporter (NET) contributes to the differences in ethanol-induced loss of righting reflex (LORR) in ILS and ISS mice. We used these mice to investigate the NET as a candidate gene contributing to this phenotype. The ILS and ISS mice carry different DNA haplotypes for NET, showing eight silent differences between allelic coding regions. Only the ILS haplotype is found in other mouse strains thus far sequenced. Brain regional analyses revealed that ILS mice have 30 to 50% lower [3H]NE uptake, NET binding, and NET mRNA levels than ISS mice. Maximal [3H]NE uptake and NET number were reduced, with no change in affinity, in the ILS mice. These neurobiological changes were associated with significant influences on the behavioral phenotype of these mice, as demonstrated by (1) a differential response in the duration of ethanol-induced LORR in ILS and ISS mice pretreated with a NET inhibitor and (2) increased ethanol-induced LORR in LXS recombinant inbred (RI) strains, homozygous for ILS in the NET chromosomal region (44-47 cM), compared with ISS homozygous strains. This is the first report to suggest that the NET gene is one of many possible genetic factors influencing ethanol sensitivity in ILS, ISS, and LXS RI mouse strains.

  14. School-Based Drug Abuse Prevention Programs in High School Students

    ERIC Educational Resources Information Center

    Sharma, Manoj; Branscum, Paul

    2013-01-01

    Drug abuse, or substance abuse, is a substantial public health problem in the United States, particularly among high school students. The purpose of this article was to review school-based programs implemented in high schools for substance abuse prevention and to suggest recommendations for future interventions. Included were English language…

  15. Hidden Abuse within the Home: Recognizing and Responding to Sibling Abuse

    ERIC Educational Resources Information Center

    Stutey, Diane; Clemens, Elysia V.

    2015-01-01

    Sibling abuse is a serious phenomenon in our society that often goes unaddressed. Victims of sibling abuse experience psychological effects similar to those of child abuse (Caspi, 2012; Wiehe, 2002). The purpose of this article is to provide school counselors with a definition of sibling abuse and a five-step model to recognize and respond. A…

  16. Sex differences in the behavioral sequelae of chronic ethanol exposure.

    PubMed

    Jury, Nicholas J; DiBerto, Jeffrey F; Kash, Thomas L; Holmes, Andrew

    2017-02-01

    Rates of alcohol use disorders (AUDs) differ between men and women, and there is also marked variation between sexes in the effects of acute and chronic alcohol. In parallel to observations in humans, prior studies in rodents have described male/female differences across a range of ethanol-related behaviors, including ethanol drinking. Nonetheless, there remain gaps in our knowledge of the role of sex in moderating the effects of ethanol, particularly in models of chronic ethanol exposure. The goal of the current study was to assess various behavioral sequelae of exposing female C57BL/6J mice to chronic intermittent ethanol (CIE) via ethanol vapors. Following four weeks of CIE exposure, adult male and female mice were compared for ethanol drinking in a two-bottle paradigm, for sensitivity to acute ethanol intoxication (via loss of righting reflex [LORR]) and for anxiety-like behaviors in the novelty-suppressed feeding and marble burying assays. Next, adult and adolescent females were tested on two different two-bottle drinking preparations (fixed or escalating ethanol concentration) after CIE. Results showed that males and females exhibited significantly blunted ethanol-induced LORR following CIE, whereas only males showed increased anxiety-like behavior after CIE. Increased ethanol drinking after CIE was also specific to males, but high baseline drinking in females may have occluded detection of a CIE-induced effect. The failure to observe elevated drinking in females in response to CIE was also seen in females exposed to CIE during adolescence, regardless of whether a fixed or escalating ethanol-concentration two-bottle procedure was employed. Collectively, these data add to the literature on sex differences in ethanol-related behaviors and provide a foundation for future studies examining how the neural consequences of CIE might differ between males and females. Published by Elsevier Inc.

  17. Sex differences in the behavioral sequelae of chronic ethanol exposure

    PubMed Central

    Jury, Nicholas J.; DiBerto, Jeffrey F.; Kash, Thomas L.; Holmes, Andrew

    2016-01-01

    Rates of alcohol use disorders (AUDs) differ between men and women, and there is also marked variation between sexes in the effects of acute and chronic alcohol. In parallel to observations in humans, prior studies in rodents have described male/female differences across a range of ethanol-related behaviors, including ethanol drinking. Nonetheless, there remain gaps in our knowledge of the role of sex in moderating the effects of ethanol, particularly in models of chronic ethanol exposure. The goal of the current study was to assess various behavioral sequelae of exposing female C57BL/6J mice to chronic intermittent ethanol (CIE) via ethanol vapors. Following four weeks of CIE exposure, adult male and female mice were compared for ethanol drinking in a two-bottle paradigm, for sensitivity to acute ethanol intoxication (via loss of righting reflex [LORR]) and for anxiety-like behaviors in the novelty-suppressed feeding and marble burying assays. Next, adult and adolescent females were tested on two different two-bottle drinking preparations (fixed or escalating ethanol concentration) after CIE. Results showed that males and females exhibited significantly blunted ethanol-induced LORR following CIE, whereas only males showed increased anxiety-like behavior after CIE. Increased ethanol drinking after CIE was also specific to males, but high baseline drinking in females may have occluded detection of a CIE-induced effect. The failure to observe elevated drinking in females in response to CIE was also seen in females exposed to CIE during adolescence, regardless of whether a fixed or escalating ethanol-concentration two-bottle procedure was employed. Collectively, these data add to the literature on sex differences in ethanol-related behaviors and provide a foundation for future studies examining how the neural consequences of CIE might differ between males and females. PMID:27624846

  18. Ethanol Basics (Fact Sheet)

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

    Not Available

    2015-01-01

    Ethanol is a widely-used, domestically-produced renewable fuel made from corn and other plant materials. More than 96% of gasoline sold in the United States contains ethanol. Learn more about this alternative fuel in the Ethanol Basics Fact Sheet, produced by the U.S. Department of Energy's Clean Cities program.

  19. The ontogeny of ethanol aversion.

    PubMed

    Saalfield, Jessica; Spear, Linda

    2016-03-15

    Recent work has suggested separate developmental periods within the broader framework of adolescence, with data suggesting distinct alterations and vulnerabilities within these intervals. While previous research has suggested reduced sensitivity to the aversive effects of alcohol in adolescence relative to adults, a more detailed ontogeny of this effect has yet to be conducted. The adolescent brain undergoes significant transitions throughout adolescence, including in regions linked with drug reward and aversion. The current study aimed to determine the ontogeny of ethanol aversion by utilizing a conditioned taste aversion procedure at six different ages to test the hypothesis that the transitions into, through, and out of adolescence are associated with ontogenetic alterations in sensitivity to the aversive properties of ethanol. Non-deprived animals given Boost® as the conditioned stimulus (CS) were used in Experiment 1, whereas Experiment 2 used water-restricted animals provided with a saccharin/sucrose solution as the CS. In both experiments, an attenuated sensitivity to the aversive properties of ethanol was evident in adolescents compared to adults, although more age differences were apparent in water deprived animals than when a highly palatable CS was given to ad libitum animals. Overall, the data suggest an attenuated sensitivity to the aversive properties of ethanol that is most pronounced during pre- and early adolescence, declining thereafter to reach the enhanced aversive sensitivity of adults. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Urine ethanol concentration and alcohol hangover severity.

    PubMed

    Van de Loo, Aurora; Mackus, Marlou; Korte-Bouws, Gerdien; Brookhuis, Karel; Garssen, Johan; Verster, Joris

    2017-01-01

    The aim of this study was to examine the relationship between urine ethanol concentration and alcohol hangover severity. N = 36 healthy social drinkers participated in a naturalistic study, comprising a hangover day and a control day. N = 18 of them have regular hangovers (the hangover group), while the other N = 18 claim to be hangover immune (hangover-immune group). On each test day at 9.30 am, urine samples were collected. Participants rated their overall hangover severity on a scale from 0 (absent) to 10 (extreme), as well as 18 individual hangover symptoms. Urine ethanol concentration was significantly higher on the hangover day when compared to the control day (p = 0.006). On the hangover day, urine ethanol concentration was significantly lower in the hangover-immune group when compared to the hangover group (p = 0.027). In the hangover-immune group, none of the correlations of urine ethanol concentration with individual hangover symptoms was significant. In contrast, in the hangover group, significant correlations were found with a variety of hangover symptoms, including nausea, concentration problems, sleepiness, weakness, apathy, sweating, stomach pain, thirst, heart racing, anxiety, and sleep problems. Urine ethanol levels are significantly associated with the presence and severity of several hangover symptoms.

  1. Dating violence victimization across the teen years: abuse frequency, number of abusive partners, and age at first occurrence.

    PubMed

    Bonomi, Amy E; Anderson, Melissa L; Nemeth, Julianna; Bartle-Haring, Suzanne; Buettner, Cynthia; Schipper, Deborah

    2012-08-10

    Prior longitudinal studies have shown high cumulative dating violence exposure rates among U.S adolescents, with 36 percent of males and 44 percent to 88 percent of females experiencing victimization across adolescence/young adulthood. Despite promising information characterizing adolescents' dating violence experiences longitudinally, prior studies tended to concentrate on physical and sexual types of violence only, and did not report information on the number of times dating violence was experienced across multiple abusive partners. We used a method similar to the timeline follow-back interview to query adolescents about dating violence victimization from age 13 to 19-including dating violence types (physical, sexual, and psychological), frequency, age at first occurrence, and number of abusive partners. A total of 730 subjects were randomly sampled from university registrar records and invited to complete an online survey, which utilized methods similar to the timeline follow-back interview, to retrospectively assess relationship histories and dating violence victimization from age 13 to 19 (eight questions adapted from widely-used surveys covering physical, sexual, and psychological abuse). Then, for each dating violence type, we asked about the number of occurrences, number of abusive partners, and age at first occurrence. Of 341 subjects who completed the survey, we included 297 (64 percent females; 36 percent males) who had a dating partner from age 13 to 19. Fully 64.7 percent of females and 61.7 percent of males reported dating violence victimization between age 13 and 19, with most experiencing multiple occurrences. More than one-third of abused females had two or more abusive partners: controlling behavior (35.6 percent); put downs/name calling (37.0); pressured sex (42.9); insults (44.3); slapped/hit (50.0); and threats (62.5). Males also had two or more abusive partners, as follows: controlling behavior (42.1 percent); insults (51.2); put downs (53

  2. Dating violence victimization across the teen years: Abuse frequency, number of abusive partners, and age at first occurrence

    PubMed Central

    2012-01-01

    Background Prior longitudinal studies have shown high cumulative dating violence exposure rates among U.S adolescents, with 36 percent of males and 44 percent to 88 percent of females experiencing victimization across adolescence/young adulthood. Despite promising information characterizing adolescents’ dating violence experiences longitudinally, prior studies tended to concentrate on physical and sexual types of violence only, and did not report information on the number of times dating violence was experienced across multiple abusive partners. We used a method similar to the timeline follow-back interview to query adolescents about dating violence victimization from age 13 to 19—including dating violence types (physical, sexual, and psychological), frequency, age at first occurrence, and number of abusive partners. Methods A total of 730 subjects were randomly sampled from university registrar records and invited to complete an online survey, which utilized methods similar to the timeline follow-back interview, to retrospectively assess relationship histories and dating violence victimization from age 13 to 19 (eight questions adapted from widely-used surveys covering physical, sexual, and psychological abuse). Then, for each dating violence type, we asked about the number of occurrences, number of abusive partners, and age at first occurrence. Of 341 subjects who completed the survey, we included 297 (64 percent females; 36 percent males) who had a dating partner from age 13 to 19. Results Fully 64.7 percent of females and 61.7 percent of males reported dating violence victimization between age 13 and 19, with most experiencing multiple occurrences. More than one-third of abused females had two or more abusive partners: controlling behavior (35.6 percent); put downs/name calling (37.0); pressured sex (42.9); insults (44.3); slapped/hit (50.0); and threats (62.5). Males also had two or more abusive partners, as follows: controlling behavior (42.1 percent

  3. Assessing the environmental sustainability of ethanol from integrated biorefineries.

    PubMed

    Falano, Temitope; Jeswani, Harish K; Azapagic, Adisa

    2014-06-01

    This paper considers the life cycle environmental sustainability of ethanol produced in integrated biorefineries together with chemicals and energy. Four types of second-generation feedstocks are considered: wheat straw, forest residue, poplar, and miscanthus. Seven out of 11 environmental impacts from ethanol are negative, including greenhouse gas (GHG) emissions, when the system is credited for the co-products, indicating environmental savings. Ethanol from poplar is the best and straw the worst option for most impacts. Land use change from forest to miscanthus increases the GHG emissions several-fold. For poplar, the effect is opposite: converting grassland to forest reduces the emissions by three-fold. Compared to fossil and first-generation ethanol, ethanol from integrated biorefineries is more sustainable for most impacts, with the exception of wheat straw. Pure ethanol saves up to 87% of GHG emissions compared to petrol per MJ of fuel. However, for the current 5% ethanol-petrol blends, the savings are much smaller (<3%). Therefore, unless much higher blends become widespread, the contribution of ethanol from integrated biorefineries to the reduction of GHG emissions will be insignificant. Yet, higher ethanol blends would lead to an increase in some impacts, notably terrestrial and freshwater toxicity as well as eutrophication for some feedstocks. © 2014 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  4. Intentional Misuse and Abuse of Loperamide: A New Look at a Drug with "Low Abuse Potential".

    PubMed

    Borron, Stephen W; Watts, Susan H; Tull, Jonathan; Baeza, Salvador; Diebold, Stephanie; Barrow, Alison

    2017-07-01

    Despite its opioid properties, loperamide has long been thought to have low abuse potential due to its poor absorption from the gastrointestinal tract and limited potential to cross the blood-brain barrier. A recent patient reportedly taking loperamide to avoid heroin withdrawal symptoms, at doses approximately 100 times those recommended, directed our attention to this issue. 1) Investigate number of cases of intentional loperamide abuse and misuse reported to poison centers between 2009 and 2015; 2) Compile reports of clinical effects of loperamide abuse; and 3) Search for evidence of increasing Internet interest in the central opioid effects of loperamide. For the years 2009 thru 2015, we reviewed exposure calls related to misuse/abuse of loperamide in the Texas Poison Center Network's database and the National Poison Data System. We used Google trend analysis to detect evidence of increased Internet interest in the illicit use of loperamide. Between 2009 and 2015, the number of misuse/abuse calls related to loperamide alone nearly doubled, with about one-third of cases occurring in teens and young adults in their 20s. Of particular concern are reports of significant cardiotoxic effects (∼18% of cases), including conduction defects and various dysrhythmias, sometimes leading to death. Google Trends analysis demonstrates an increasing number of searches for "loperamide high" and "loperamide withdrawal" beginning in 2011. Loperamide misuse/abuse seems to be on the rise. Given its propensity to induce conduction disturbances and dysrhythmias at very high doses, emergency physicians should be vigilant for this form of drug abuse. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Abuse Is Abuse: The Influence of Type of Abuse, Victim Age, and Defendant Age on Juror Decision Making.

    PubMed

    Sheahan, Chelsea L; Pica, Emily; Pozzulo, Joanna D

    2017-09-01

    The purpose of the current study was to examine the role of victim age, defendant age, and type of abuse on mock juror decision making. Mock jurors ( N = 556) read a trial transcript in which a soccer coach was accused of sexual abuse or physical abuse against a player. The victim's age (child, adolescent, or young adult), the defendant's age (young, middle age, or older adult), and the type of abuse (sexual or physical) were varied. Mock jurors provided a dichotomous and continuous verdict and rated their perceptions of the victim and the defendant. Although no differences on mock jurors' dichotomous verdict were found due to victim age, defendant age, or type of abuse, mock jurors provided higher guilt ratings when the abuse was sexual and both the victim and defendant were described as young adults. Similarly, mock jurors rated the victim more positively when the victim was described as a young adult (vs. child) for both sexual and physical abuse cases, and rated the defendant more positively when the victim was described as a child compared with young adult in sexual abuse cases. These findings suggest that mock jurors were largely influenced by victim age, particularly when the victim was described as an adult compared with a child.

  6. Preventing Child Abuse: A Meta-Analysis of Parent Training Programs

    ERIC Educational Resources Information Center

    Lundahl, Brad W.; Nimer, Janelle; Parsons, Bruce

    2006-01-01

    Objective: A meta-analysis was conducted to evaluate the ability of parent training programs to reduce parents' risk of abusing a child. Method: A total of 23 studies were submitted to a meta-analysis. Outcomes of interest included parents' attitudes toward abuse, emotional adjustment, child-rearing skills, and actual abuse. Conclusions:…

  7. The management of abuse: 2. Child abuse.

    PubMed

    Panesear, Jaspel; Sinha, Karen Juggins Sonia; Acharya, Preeti; Jafar, Hima; Bower, Elizabeth J; Harrison, Victoria E; Newton, J Tim

    2006-09-01

    The role of the GDP and the dental team in the recognition and management of child abuse is discussed. Information on the current legislation and protocols for referral are provided. This paper discusses child abuse and offers information and practical advice for the dental team.

  8. [Suspected child abuse in paediatric emergency service].

    PubMed

    Sabaté Rotés, A; Sancosmed Ron, M; Cebrián Rubio, R; Canet Ponsa, M; Martín González, M

    2009-07-01

    To describe the epidemiology of child abuse in an emergency department of a tertiary paediatric hospital. Descriptive and retrospective study from January 2008 to January 2006 including patients less than sixteen years of age who were suspected of being abused during the examination in the emergency department. Child maltreatment was 0.07% of all paediatric emergencies (45% physical abuse, 35% sexual abuse and 20% neglect). Mean age of 6 years old, with no gender differences. 86% were suspected of maltreatment. An adult living with the child was suspected in 67% of cases. Social and judicial procedures were activated. A total of 24 children were admitted, 14 under medical criteria and the rest in order to protect the child; 2 had serious neurological consequences and one died. Eight patients were discharged to social service care centres. We believe it is necessary to improve the pediatrician's knowledge of child abuse and to create specialized units.

  9. [Child psychiatric assessment and the debate regarding the abuse of abuse].

    PubMed

    Fegert, J M

    1995-03-01

    The current discussion on false allegations in sexual abuse cases has led to a polarization in the views expressed about the credibility of children. Some authors even speak of a "child sexual accuse syndrome" or of a "sexual abuse allegation in divorce" (SAID) syndrome. A phenomenological analysis of the multiple reasons for misinterpretations is presented. Instead of stressing the importance only of false positives in child sexual abuse questions, an attempt is made to describe reasons for false negatives. Based on a retrospective analysis of 50 consecutive child psychiatric experts in connection with court cases, there does not appear to be an increase in false accusations. Rather, only about one third of the cases even involved suspected sexual abuse. Sexual abuse allegations were much more frequent in girls than in boys. Of 20 abuse allegations we judge four to be false allegations. In only one of these cases, that of an adolescent girl who had been abused in childhood, was the false allegation intended.

  10. Stereological study of rat spleen following acute ethanol treatment.

    PubMed

    Budec, M; Milićević, Z; Koko, V

    2000-05-01

    To investigate the acute effect of ethanol (4 g/kg, i.p.) on spleen adult female Wistar rats were treated intraperitoneally with: a) ethanol (4 g/kg body wt), b) naltrexone (5 mg/kg body wt) followed 45 minutes later by ethanol (4 g/kg body wt) and c) naltrexone (5 mg/kg body wt) alone. Untreated and saline-treated rats were used as controls. Twenty hours after the ethanol treatment the animals were sacrificed and the spleens were removed. A piece of tissue from the central part of each organ was fixed in Bouin's solution. Paraffin sections were stained with hematoxylin-eosin and analysed using stereological measurements. The volume densities of the following tissue compartments: red pulp, white pulp (divided in follicles, periarterioral lymphatic sheath and marginal zone) and the connective tissue were determined. Stereological analysis also included parameters of follicles: the areal numerical density (the number of follicles per 1 mm2 of tissue section), the numerical density (the number of follicles per mm3 of tissue) and the mean follicle diameter. The immunoarchitecture of the spleen was preserved following acute ethanol treatment. Unlike other parameters that were unaffected, ethanol evoked a decrease in both volume density of follicle and the mean follicle diameter. Naltrexone pretreatment had no influence on ethanol-induced changes. The data obtained indicate that a single dose of ethanol has a profound effect on rat spleen affecting the follicles, but the mechanism of its action remains to be elucidated.

  11. Student Assistance Programs: An Important Approach to Drug Abuse Prevention.

    ERIC Educational Resources Information Center

    McGovern, John P.; DuPont, Robert L.

    1991-01-01

    Describes a new approach to school-based drug abuse prevention called Student Assistance Programs (SAP). SAP offers various approaches tailored to particular settings and includes students, teachers, parents, and community representatives who define and resolve student problems including substance abuse. SAP facilitates the use of 12-step…

  12. Transesterification of waste vegetable oil under pulse sonication using ethanol, methanol and ethanol-methanol mixtures.

    PubMed

    Martinez-Guerra, Edith; Gude, Veera Gnaneswar

    2014-12-01

    This study reports on the effects of direct pulse sonication and the type of alcohol (methanol and ethanol) on the transesterification reaction of waste vegetable oil without any external heating or mechanical mixing. Biodiesel yields and optimum process conditions for the transesterification reaction involving ethanol, methanol, and ethanol-methanol mixtures were evaluated. The effects of ultrasonic power densities (by varying sample volumes), power output rates (in W), and ultrasonic intensities (by varying the reactor size) were studied for transesterification reaction with ethanol, methanol and ethanol-methanol (50%-50%) mixtures. The optimum process conditions for ethanol or methanol based transesterification reaction of waste vegetable oil were determined as: 9:1 alcohol to oil ratio, 1% wt. catalyst amount, 1-2 min reaction time at a power output rate between 75 and 150 W. It was shown that the transesterification reactions using ethanol-methanol mixtures resulted in biodiesel yields as high as >99% at lower power density and ultrasound intensity when compared to ethanol or methanol based transesterification reactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Lesion of the rostromedial tegmental nucleus increases voluntary ethanol consumption and accelerates extinction of ethanol-induced conditioned taste aversion.

    PubMed

    Sheth, Chandni; Furlong, Teri M; Keefe, Kristen A; Taha, Sharif A

    2016-10-01

    Ethanol has rewarding and aversive properties, and the balance of these properties influences voluntary ethanol consumption. Preclinical and clinical evidence show that the aversive properties of ethanol limit intake. The neural circuits underlying ethanol-induced aversion learning are not fully understood. We have previously shown that the lateral habenula (LHb), a region critical for aversive conditioning, plays an important role in ethanol-directed behaviors. However, the neurocircuitry through which LHb exerts its actions is unknown. In the present study, we investigate a role for the rostromedial tegmental nucleus (RMTg), a major LHb projection target, in regulating ethanol-directed behaviors. Rats received either sham or RMTg lesions and were studied during voluntary ethanol consumption; operant ethanol self-administration, extinction, and yohimbine-induced reinstatement of ethanol-seeking; and ethanol-induced conditioned taste aversion (CTA). RMTg lesions increased voluntary ethanol consumption and accelerated extinction of ethanol-induced CTA. The RMTg plays an important role in regulating voluntary ethanol consumption, possibly by mediating ethanol-induced aversive conditioning.

  14. Abuse Tolerance Improvements

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

    Orendorff, Christopher J.; Nagasubramanian, Ganesan; Fenton, Kyle R.

    As lithium-ion battery technologies mature, the size and energy of these systems continues to increase (> 50 kWh for EVs); making safety and reliability of these high energy systems increasingly important. While most material advances for lithium-ion chemistries are directed toward improving cell performance (capacity, energy, cycle life, etc.), there are a variety of materials advancements that can be made to improve lithium-ion battery safety. Issues including energetic thermal runaway, electrolyte decomposition and flammability, anode SEI stability, and cell-level abuse tolerance continue to be critical safety concerns. This report highlights work with our collaborators to develop advanced materials to improvemore » lithium-ion battery safety and abuse tolerance and to perform cell-level characterization of new materials.« less

  15. Ethanol-induced locomotor activity in adolescent rats and the relationship with ethanol-induced conditioned place preference and conditioned taste aversion.

    PubMed

    Acevedo, María Belén; Nizhnikov, Michael E; Spear, Norman E; Molina, Juan C; Pautassi, Ricardo M

    2013-05-01

    Adolescent rats exhibit ethanol-induced locomotor activity (LMA), which is considered an index of ethanol's motivational properties likely to predict ethanol self-administration, but few studies have reported or correlated ethanol-induced LMA with conditioned place preference (CPP) by ethanol at this age. The present study assessed age-related differences in ethanol's motor stimulating effects and analyzed the association between ethanol-induced LMA and conventional measures of ethanol-induced reinforcement. Experiment 1 compared ethanol-induced LMA in adolescent and adult rats. Subsequent experiments analyzed ethanol-induced CPP and conditioned taste aversion (CTA) in adolescent rats evaluated for ethanol-induced LMA. Adolescent rats exhibit a robust LMA after high-dose ethanol. Ethanol-induced LMA was fairly similar across adolescents and adults. As expected, adolescents were sensitive to ethanol's aversive reinforcement, but they also exhibited CPP. These measures of ethanol reinforcement, however, were not related to ethanol-induced LMA. Spontaneous LMA in an open field was, however, negatively associated with ethanol-induced CTA. Copyright © 2012 Wiley Periodicals, Inc.

  16. Abuse-Deterrent Formulations and the Prescription Opioid Abuse Epidemic in the United States: Lessons Learned From OxyContin.

    PubMed

    Cicero, Theodore J; Ellis, Matthew S

    2015-05-01

    indicated experience using pre-ADF and ADF OxyContin, this residual level of abuse reflects the following 3 phenomena: (1) a transition from nonoral routes of administration to oral use (38 participants [43%]); (2) successful efforts to defeat the ADF mechanism leading to a continuation of inhaled or injected use (30 participants [34%]); and (3) exclusive use of the oral route independent of formulation type (20 participants [23%]). Abuse-deterrent formulations can have the intended purpose of curtailing abuse, but the extent of their effectiveness has clear limits, resulting in a significant level of residual abuse. Consequently, although drug abuse policy should focus on limiting supplies of prescription analgesics for abuse, including ADF technology, efforts to reduce supply alone will not mitigate the opioid abuse problem in this country.

  17. Coping capacity among women with abusive partners.

    PubMed

    Nurius, P S; Furrey, J; Berliner, L

    1992-01-01

    Coping capacity, although increasingly implicated as a mediating force in how individuals respond to personal threat, is an underrecognized factor in work with women of abusive partners. To explore the utility of coping capacity as a multivariable set to guide intervention with women of abusive partners, findings are reported comparing four groups of women: those whose partners do not engage in abuse, are abusive toward them, are sex offenders of children for whom the woman is a parent, or are offenders of children for whom the woman is not a parent. Three variable sets were included: vulnerability factors that may negatively influence appraisals of threat and ability to cope with abuse; coping responses that include cognitive, emotional, and behavioral reactions to the abuse; and coping resources expected to mediate effects of vulnerability factors and to influence the mobilization (of lack thereof) of coping responses. There were significant differences in coping capacity profiles across the four groups. These appeared to be a continuum of coping capacity, with women who were most directly threatened showing the lowest and women who were least directly threatened showing the highest levels of coping capacity. In order from the lowest to the highest levels of coping capacity were (1) battered women, (2) women whose partners are offenders against their children, (3) women whose partners are offenders against children of whom they are not the parent, and (4) control group women. The paper ends with a conceptual interpretation of the mediating functions of coping resources and implications for intervention and further study.

  18. Prenatal drug exposure effects on subsequent vulnerability to drug abuse.

    PubMed

    Glantz, Meyer D; Chambers, Jessica Campbell

    2006-01-01

    Research has shown that both prenatal alcohol and tobacco exposure are associated with increased risk of significant adverse medical, developmental, and behavioral outcomes including substance abuse. Research on the outcomes of prenatal exposure to illicit drugs (PNDE) has also found increased physical and behavioral problems for gestationally drug-exposed children. However, a clear picture has not emerged on whether the consequences of PNDE are independent from those associated with having a substance abusing parent and whether PNDE increases vulnerability to drug abuse. Because of its typical co-occurrence with factors inherent in having a drug-abusing parent, PNDE is at least a marker of significant increased risk for a range of negative outcomes including greater vulnerability to substance abuse. Although a review of the relevant research literatures indicates that the direct consequences of PNDE appear to be generally both subtle and nonglobal, PNDE does appear to have negative developmental and behavioral outcomes, and there is evidence that it is a modest direct contributor to increased substance abuse vulnerability.

  19. Child Abuse in Young, HIV-Positive Women: Linkages to Risk

    PubMed Central

    Clum, Gretchen A.; Andrinopoulos, Katherine; Muessig, Kathryn; Ellen, Jonathan M.

    2010-01-01

    In this article we explore the lives of young women living with HIV who experienced physical and/or sexual abuse in childhood. Using a modified version of the Life Story Interview, 40 women recruited from HIV clinics in three different states participated in a qualitative interview. Interviews covered abuse experiences, cognitive and emotional consequences of abuse, coping strategies, and sexual behavior and relationships. Overall, these young women had complex abuse histories, often experiencing more than one type of abuse in the context of other difficult life events. Avoidance and substance use were frequently utilized as coping strategies for abuse-related distress. Young women reported sexual and relationship concerns, including avoidance of sex, sexual dysfunction, sex as a trigger for abuse memories, and difficulty establishing intimacy and trust. Relationships between abuse-related reactions and sexual risk behavior, as well as recommendations for interventions, are discussed. PMID:19949224

  20. Child Peer Sexual Abuse: Preliminary Data on Outcomes and Disclosure Experiences

    ERIC Educational Resources Information Center

    Sperry, Debbie M.; Gilbert, Brenda O.

    2005-01-01

    Objective: This study compared experiences of children sexually abused by peers to those of children abused by adolescents/adults. Variables examined included perceived negativity of the abuse, self-reported outcomes, overall psychological functioning, and disclosure. Method: An archival data set containing retrospective reports of childhood…

  1. Process for producing ethanol from plant biomass using the fungus paecilomyces sp.

    DOEpatents

    Wu, Jung Fu

    1989-01-01

    A process for producing ethanol from plant biomass is disclosed. The process in cludes forming a substrate from the biomass with the substrate including hydrolysates of cellulose and hemicellulose. A species of the fungus Paecilomyces, which has the ability to ferment both cellobiose and xylose to ethanol, is then selected and isolated. The substrate is inoculated with this fungus, and the inoculated substrate is then fermented under conditions favorable for cell viability and conversion of hydrolysates to ethanol. Finally, ethanol is recovered from the fermented substrate.

  2. Stress in adolescence and drugs of abuse in rodent models: Role of dopamine, CRF, and HPA axis

    PubMed Central

    Burke, Andrew R.; Miczek, Klaus A.

    2014-01-01

    Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse. Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic pituitary adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms. Results and Conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse. PMID:24370534

  3. Ethanol production by engineered thermophiles.

    PubMed

    Olson, Daniel G; Sparling, Richard; Lynd, Lee R

    2015-06-01

    We compare a number of different strategies that have been pursued to engineer thermophilic microorganisms for increased ethanol production. Ethanol production from pyruvate can proceed via one of four pathways, which are named by the key pyruvate dissimilating enzyme: pyruvate decarboxylase (PDC), pyruvate dehydrogenase (PDH), pyruvate formate lyase (PFL), and pyruvate ferredoxin oxidoreductase (PFOR). For each of these pathways except PFL, we see examples where ethanol production has been engineered with a yield of >90% of the theoretical maximum. In each of these cases, this engineering was achieved mainly by modulating expression of native genes. We have not found an example where a thermophilic ethanol production pathway has been transferred to a non-ethanol-producing organism to produce ethanol at high yield. A key reason for the lack of transferability of ethanol production pathways is the current lack of understanding of the enzymes involved. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Alcoholism and Alcohol Abuse

    MedlinePlus

    ... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... the liver, brain, and other organs. Drinking during pregnancy can harm your baby. Alcohol also increases the ...

  5. Pavlovian conditioning and ethanol tolerance.

    PubMed

    Siegel, S

    1987-01-01

    Results of considerable amount of research indicate that Pavlovian conditional pharmacological responses, resulting from repeated pairings of ethanol-associated environmental cues with the systemic effects of ethanol, importantly contribute to ethanol tolerance.

  6. Improving detection and quality of assessment of child abuse and partner abuse is achievable with a formal organisational change approach.

    PubMed

    Wills, Russell; Ritchie, Miranda; Wilson, Mollie

    2008-03-01

    To improve detection and quality of assessment of child and partner abuse within a health service. A formal organisational change approach was used to implement the New Zealand Family Violence Intervention Guidelines in a mid-sized regional health service. The approach includes obtaining senior management support, community collaboration, developing resources to support practice, research, evaluation and training. Formal pre-post evaluations were conducted of the training. Barriers and enablers of practice change were assessed through 85 interviews with 60 staff. More than 6000 clinical records were audited to assess rates of questioning for partner abuse. Identifications of partner abuse and referrals made were counted through the Family Violence Accessory File. Referrals to the Department of Child, Youth and Family Services (CYFS) were recorded routinely by the CYFS. Audits assessed quality of assessment of child and partner abuse, when identified. More than 700 staff were trained in dual assessment for child and partner abuse. Evaluations demonstrate improved confidence following training, though staff still need support. Barriers and enablers to asking about partner abuse were identified. Referrals from the health service to the CYFS increased from 10 per quarter to 70 per quarter. Identification of partner abuse increased from 30 to 80 per 6-month period. Routine questioning rates for partner abuse vary between services. Achieving and sustaining improved rates of identification and quality of assessment of child and partner abuse is possible with a formal organisational change approach.

  7. Alternative Fuels Data Center: Ethanol

    Science.gov Websites

    ... Ethanol Basics Benefits & Considerations Stations Vehicles Laws & Incentives Ethanol Fuel Prices of a scale. Benefits and Considerations Explore the benefits and considerations of using ethanol as a

  8. Establishing a Short Term Program Component To Build Self-Esteem in a Small Group of Abusive and Potentially Abusive Parents.

    ERIC Educational Resources Information Center

    Zimmerman, Judith

    This practicum was designed to enhance the self-esteem of abusive and potentially abusive parents. A combination of strategies was used to enhance self-esteem and to help parents solve problems in an appropriate manner. The intervention strategy included three objectives: (1) gain the confidence of the participants; (2) use a curriculum that…

  9. Evaluation of direct and indirect ethanol biomarkers using a likelihood ratio approach to identify chronic alcohol abusers for forensic purposes.

    PubMed

    Alladio, Eugenio; Martyna, Agnieszka; Salomone, Alberto; Pirro, Valentina; Vincenti, Marco; Zadora, Grzegorz

    2017-02-01

    The detection of direct ethanol metabolites, such as ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs), in scalp hair is considered the optimal strategy to effectively recognize chronic alcohol misuses by means of specific cut-offs suggested by the Society of Hair Testing. However, several factors (e.g. hair treatments) may alter the correlation between alcohol intake and biomarkers concentrations, possibly introducing bias in the interpretative process and conclusions. 125 subjects with various drinking habits were subjected to blood and hair sampling to determine indirect (e.g. CDT) and direct alcohol biomarkers. The overall data were investigated using several multivariate statistical methods. A likelihood ratio (LR) approach was used for the first time to provide predictive models for the diagnosis of alcohol abuse, based on different combinations of direct and indirect alcohol biomarkers. LR strategies provide a more robust outcome than the plain comparison with cut-off values, where tiny changes in the analytical results can lead to dramatic divergence in the way they are interpreted. An LR model combining EtG and FAEEs hair concentrations proved to discriminate non-chronic from chronic consumers with ideal correct classification rates, whereas the contribution of indirect biomarkers proved to be negligible. Optimal results were observed using a novel approach that associates LR methods with multivariate statistics. In particular, the combination of LR approach with either Principal Component Analysis (PCA) or Linear Discriminant Analysis (LDA) proved successful in discriminating chronic from non-chronic alcohol drinkers. These LR models were subsequently tested on an independent dataset of 43 individuals, which confirmed their high efficiency. These models proved to be less prone to bias than EtG and FAEEs independently considered. In conclusion, LR models may represent an efficient strategy to sustain the diagnosis of chronic alcohol consumption

  10. An assay for evoked locomotor behavior in Drosophila reveals a role for integrins in ethanol sensitivity and rapid ethanol tolerance.

    PubMed

    Bhandari, Poonam; Kendler, Kenneth S; Bettinger, Jill C; Davies, Andrew G; Grotewiel, Mike

    2009-10-01

    Ethanol induces similar behavioral responses in mammals and the fruit fly, Drosophila melanogaster. By coupling assays for ethanol-related behavior to the genetic tools available in flies, a number of genes have been identified that influence physiological responses to ethanol. To enhance the utility of the Drosophila model for investigating genes involved in ethanol-related behavior, we explored the value of an assay that measures the sedative effects of ethanol on negative geotaxis, an evoked locomotor response. We established eRING (ethanol Rapid Iterative Negative Geotaxis) as an assay for quantitating the sedative effects of ethanol on negative geotaxis (i.e., startle-induced climbing). We validated the assay by assessing acute sensitivity to ethanol and rapid ethanol tolerance in several different control strains and in flies with mutations known to disrupt these behaviors. We also used eRING in a candidate screen to identify mutants with altered ethanol-related behaviors. Negative geotaxis measured in eRING assays was dose-dependently impaired by ethanol exposure. Flies developed tolerance to the intoxicating effects of ethanol when tested during a second exposure. Ethanol sensitivity and rapid ethanol tolerance varied across 4 control strains, but internal ethanol concentrations were indistinguishable in the 4 strains during a first and second challenge with ethanol. Ethanol sensitivity and rapid ethanol tolerance, respectively, were altered in flies with mutations in amnesiac and hangover, genes known to influence these traits. Additionally, mutations in the beta integrin gene myospheroid and the alpha integrin gene scab increased the initial sensitivity to ethanol and enhanced the development of rapid ethanol tolerance without altering internal ethanol concentrations. The eRING assay is suitable for investigating genetic mechanisms that influence ethanol sensitivity and rapid ethanol tolerance. Ethanol sensitivity and rapid ethanol tolerance depend on the

  11. Sexual maturation and control issues among sexually abused and non-abused anorexia patients.

    PubMed

    Walsh, J; Burns, F

    2000-09-01

    To assess the relative salience of the maintenance of control and the avoidance of sexual maturation as sources of motivation for maintaining pathological eating behaviours among sexually abused anorexic patients. A two-factor mixed experimental design was employed. Three independent groups (sexually abused anorexics (N = 12); non-abused anorexics (N = 9); non-anorexic/non-abused controls (N = 12)) constituted the between-subjects factor. Allocation to abuse/non-abuse group was dependent upon replies to a questionnaire-based measure of unwanted sexual experience. The within-subjects factor comprised three conditions in which words of various colours were presented to participants for colour-naming (Stroop, 1935). The conditions were represented by lists of neutral words, sexual maturation words, and control-related words. Two trials were carried out in each condition and mean response times were measured. Within-group analyses revealed that interference was greater from sexual maturation words than from control-related words among the sexually-abused anorexics, but of equal magnitude among non-abused counterparts. Between-groups analyses found that abused patients experienced marginally greater cognitive interference from sexual maturation words than the non-abused patients. Theoretically, support is offered for elaborated schematic models of cognitive processing. Clinically, treatment interventions may need to pay particular attention to issues of sexual maturation among sexually abused anorexic patients.

  12. Fetal Alcohol Syndrome, Chemo-Biology and OMICS: Ethanol Effects on Vitamin Metabolism During Neurodevelopment as Measured by Systems Biology Analysis

    PubMed Central

    Feltes, Bruno César; de Faria Poloni, Joice; Nunes, Itamar José Guimarães

    2014-01-01

    Abstract Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the interplay between ethanol metabolism and vitamins during mouse neurodevelopment. For this purpose, we designed interactomes and employed transcriptomic data analysis approaches to study the neural tissue of Mus musculus exposed to ethanol prenatally and postnatally, simulating conditions that could lead to FAS development at different life stages. Our results showed that FAS can promote early changes in neurotransmitter release and glutamate equilibrium, as well as an abnormal calcium influx that can lead to neuroinflammation and impaired neurodifferentiation, both extensively connected with vitamin action and metabolism. Genes related to retinoic acid, niacin, vitamin D, and folate metabolism were underexpressed during neurodevelopment and appear to contribute to neuroinflammation progression and impaired synapsis. Our results also indicate that genes coding for tubulin, tubulin-associated proteins, synapse plasticity proteins, and proteins related to neurodifferentiation are extensively affected by ethanol exposure. Finally, we developed a molecular model of how ethanol can affect vitamin metabolism and impair neurodevelopment. PMID:24816220

  13. Fetal alcohol syndrome, chemo-biology and OMICS: ethanol effects on vitamin metabolism during neurodevelopment as measured by systems biology analysis.

    PubMed

    Feltes, Bruno César; de Faria Poloni, Joice; Nunes, Itamar José Guimarães; Bonatto, Diego

    2014-06-01

    Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the interplay between ethanol metabolism and vitamins during mouse neurodevelopment. For this purpose, we designed interactomes and employed transcriptomic data analysis approaches to study the neural tissue of Mus musculus exposed to ethanol prenatally and postnatally, simulating conditions that could lead to FAS development at different life stages. Our results showed that FAS can promote early changes in neurotransmitter release and glutamate equilibrium, as well as an abnormal calcium influx that can lead to neuroinflammation and impaired neurodifferentiation, both extensively connected with vitamin action and metabolism. Genes related to retinoic acid, niacin, vitamin D, and folate metabolism were underexpressed during neurodevelopment and appear to contribute to neuroinflammation progression and impaired synapsis. Our results also indicate that genes coding for tubulin, tubulin-associated proteins, synapse plasticity proteins, and proteins related to neurodifferentiation are extensively affected by ethanol exposure. Finally, we developed a molecular model of how ethanol can affect vitamin metabolism and impair neurodevelopment.

  14. Imaging Findings in Elder Abuse: A Role for Radiologists in Detection.

    PubMed

    Wong, Natalie Z; Rosen, Tony; Sanchez, Allen M; Bloemen, Elizabeth M; Mennitt, Kevin W; Hentel, Keith; Nicola, Refky; Murphy, Kieran J; LoFaso, Veronica M; Flomenbaum, Neal E; Lachs, Mark S

    2017-02-01

    Emergency department assessment represents a critical but often missed opportunity to identify elder abuse, which is common and has serious consequences. Among emergency care providers, diagnostic radiologists are optimally positioned to raise suspicion for mistreatment when reviewing imaging of geriatric injury victims. However, little literature exists describing relevant injury patterns, and most radiologists currently receive neither formal nor informal training in elder abuse identification. We present 2 cases to begin characterisation of the radiographic findings in elder abuse. Findings from these cases demonstrate similarities to suspicious findings in child abuse including high-energy fractures that are inconsistent with reported mechanisms and the coexistence of acute and chronic injuries. Specific injuries uncommon to accidental injury are also noted, including a distal ulnar diaphyseal fracture. We hope to raise awareness of elder abuse among diagnostic radiologists to encourage future large-scale research, increased focus on chronic osseous findings, and the addition of elder abuse to differential diagnoses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Ethanol-diesel fuel blends -- a review.

    PubMed

    Hansen, Alan C; Zhang, Qin; Lyne, Peter W L

    2005-02-01

    Ethanol is an attractive alternative fuel because it is a renewable bio-based resource and it is oxygenated, thereby providing the potential to reduce particulate emissions in compression-ignition engines. In this review the properties and specifications of ethanol blended with diesel fuel are discussed. Special emphasis is placed on the factors critical to the potential commercial use of these blends. These factors include blend properties such as stability, viscosity and lubricity, safety and materials compatibility. The effect of the fuel on engine performance, durability and emissions is also considered. The formulation of additives to correct certain key properties and maintain blend stability is suggested as a critical factor in ensuring fuel compatibility with engines. However, maintaining vehicle safety with these blends may entail fuel tank modifications. Further work is required in specifying acceptable fuel characteristics, confirming the long-term effects on engine durability, and ensuring safety in handling and storing ethanol-diesel blends.

  16. Re-evaluation of the reward comparison hypothesis for alcohol abuse.

    PubMed

    He, Alan Bo-Han; Chang, Yu-Chieh; Meng, Anna Wan Yun; Huang, Andrew Chih Wei

    2017-08-14

    This study examined whether various doses of ethanol induced reward or aversion and then evaluated Grigson's reward comparison hypothesis (1997). Rats were given a 0.1% saccharin solution (conditioned stimulus 1 [CS1]) 15min prior to administration of a 0, 0.05, 0.125, 0.20, 0.35, or 0.50g/kg dose of ethanol (unconditioned stimulus [US]). The rats were then exposed to a paired compartment (CS2) for 30min. The low dose of 0.05g/kg ethanol did not induce conditioned suppression (i.e., conditioned taste aversion [CTA]) or conditioned place preference (CPP). The dose of 0.125g/kg ethanol induced CPP but not CTA. High doses of ethanol, including 0.35g/kg and 0.50g/kg, produced CTA but not CPP. The middle dose of 0.20g/kg ethanol simultaneously induced CTA and CPP. As a result, the reward comparison hypothesis cannot explain the present finding that the middle dose of ethanol induced CTA and CPP. Meanwhile, the high doses of ethanol induced motivationally aversive CTA but not rewarding CPP. The reward comparison hypothesis should be updated further. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Pediatric ingestions of house hold products containing ethanol: a review.

    PubMed

    Rayar, Praveen; Ratnapalan, Savithiri

    2013-03-01

    Alcohol is present in a number of household items that are readily accessible to children. Ingestion of these household products containing alcohol can lead to significant health risks. To identify reported cases of ingestions of common household items that have led to ethanol intoxication, poisoning, or death in children up to the age of 18 years. The OVID MEDLINE database from 1948 to March 2011, Embase from 1980 to March 2011, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) from 1982 to February 2011 were searched for articles with the following key terms: alcohols(ethanol or ethyl alcohol) and ingest*(ingestion) or intoxic*(intoxication) or poisoning* or death. The search was limited to children (0-18 years). All articles that reported ingestion of household products that contained ethanol were included in the analysis. Results. Many household products, particularly mouthwashes, hand sanitizers, and cosmetics contain quantities of ethanol that are significant enough to induce intoxication and hypoglycemia. There were 17 publications directly reporting on children with alcohol intoxication from household products. Serious adverse events included hypoglycemia, seizures, and death. Child-resistant closures appear to have reduced the incidence of ingestion of ethanol-based products, including mouthwashes, and may be applicable to other products such as hand sanitizers. Ingestion of household substances containing alcohol continues to be a health care problem. Legislature to reduce alcohol content in household products and public education should be instituted to prevent poisonings in children.

  18. Psychological abuse, substance abuse distress, dissatisfaction with friendships, and incident psychiatric problems.

    PubMed

    Sheikh, Mashhood Ahmed

    2018-05-01

    The aim of this study was to assess the mediating role of dissatisfaction with friendships in adulthood in the associations between psychological abuse in childhood, substance abuse distress in childhood, and incident psychiatric problems (IPPs) in adulthood over 13 years of follow-up. We used data collected from 1994 to 2008 within the framework of the Tromsø Study (N = 9502), a representative, longitudinal, prospective cohort study. Poisson regression analysis was used to assess the associations between psychological abuse, substance abuse distress, dissatisfaction with friendships in adulthood, and IPPs in adulthood. Indirect effects and proportion mediated (%) were assessed with the difference-in-coefficients method. Psychological abuse (relative risk [RR] = 1.66, 95% confidence interval [CI]: 1.45-1.89) and substance abuse distress in childhood (RR = 1.38, 95% CI: 1.18-1.62) were associated with an increased risk of dissatisfaction with friendships in adulthood. Dissatisfaction with friendships in adulthood was associated with an increased risk of IPPs in adulthood (RR = 1.71, 95% CI: 1.33-2.20). Moreover, dissatisfaction with friendships in adulthood mediated 9.31% (95% CI: 4.25-14.57) of the association between psychological abuse in childhood and IPPs in adulthood, and 9.17% (95% CI: 4.35-16.33) of the association between substance abuse distress in childhood and IPPs in adulthood. Dissatisfaction with friendships in adulthood mediates a minor proportion of the associations between psychological abuse, substance abuse distress, and IPPs in adulthood. Interventions aimed at decreasing dissatisfaction with friendships may dampen some of the effect of psychological abuse and substance abuse distress in childhood on IPPs in adulthood. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Effects of production and market factors on ethanol profitability for an integrated first and second generation ethanol plant using the whole sugarcane as feedstock.

    PubMed

    Macrelli, Stefano; Galbe, Mats; Wallberg, Ola

    2014-02-21

    Sugarcane is an attractive feedstock for ethanol production, especially if the lignocellulosic fraction can also be treated in second generation (2G) ethanol plants. However, the profitability of 2G ethanol is affected by the processing conditions, operating costs and market prices. This study focuses on the minimum ethanol selling price (MESP) and maximum profitability of ethanol production in an integrated first and second generation (1G + 2G) sugarcane-to-ethanol plant. The feedstock used was sugarcane juice, bagasse and leaves. The lignocellulosic fraction was hydrolysed with enzymes. Yields were assumed to be 95% of the theoretical for each of the critical steps in the process (steam pretreatment, enzymatic hydrolysis (EH), fermentation, solid/liquid separation, anaerobic digestion) in order to obtain the best conditions possible for ethanol production, to assess the lowest production costs. Techno-economic analysis was performed for various combinations of process options (for example use of pentoses, addition of leaves), EH conditions (water-insoluble solids (WIS) and residence time), operating cost (enzymes) and market factors (wholesale prices of electricity and ethanol, cost of the feedstock). The greatest reduction in 2G MESP was achieved when using the pentoses for the production of ethanol rather than biogas. This was followed, in decreasing order, by higher enzymatic hydrolysis efficiency (EHE), by increasing the WIS to 30% and by a short residence time (48 hours) in the EH. The addition of leaves was found to have a slightly negative impact on 1G + 2G MESP, but the effect on 2G MESP was negligible. Sugarcane price significantly affected 1G + 2G MESP, while the price of leaves had a much lower impact. Net present value (NPV) analysis of the most interesting case showed that integrated 1G + 2G ethanol production including leaves could be more profitable than 1G ethanol, despite the fact that the MESP was higher than in 1G ethanol

  20. Effects of production and market factors on ethanol profitability for an integrated first and second generation ethanol plant using the whole sugarcane as feedstock

    PubMed Central

    2014-01-01

    Background Sugarcane is an attractive feedstock for ethanol production, especially if the lignocellulosic fraction can also be treated in second generation (2G) ethanol plants. However, the profitability of 2G ethanol is affected by the processing conditions, operating costs and market prices. This study focuses on the minimum ethanol selling price (MESP) and maximum profitability of ethanol production in an integrated first and second generation (1G + 2G) sugarcane-to-ethanol plant. The feedstock used was sugarcane juice, bagasse and leaves. The lignocellulosic fraction was hydrolysed with enzymes. Yields were assumed to be 95% of the theoretical for each of the critical steps in the process (steam pretreatment, enzymatic hydrolysis (EH), fermentation, solid/liquid separation, anaerobic digestion) in order to obtain the best conditions possible for ethanol production, to assess the lowest production costs. Techno-economic analysis was performed for various combinations of process options (for example use of pentoses, addition of leaves), EH conditions (water-insoluble solids (WIS) and residence time), operating cost (enzymes) and market factors (wholesale prices of electricity and ethanol, cost of the feedstock). Results The greatest reduction in 2G MESP was achieved when using the pentoses for the production of ethanol rather than biogas. This was followed, in decreasing order, by higher enzymatic hydrolysis efficiency (EHE), by increasing the WIS to 30% and by a short residence time (48 hours) in the EH. The addition of leaves was found to have a slightly negative impact on 1G + 2G MESP, but the effect on 2G MESP was negligible. Sugarcane price significantly affected 1G + 2G MESP, while the price of leaves had a much lower impact. Net present value (NPV) analysis of the most interesting case showed that integrated 1G + 2G ethanol production including leaves could be more profitable than 1G ethanol, despite the fact that the MESP was higher than

  1. Chronic intermittent ethanol exposure during adolescence: effects on social behavior and ethanol sensitivity in adulthood.

    PubMed

    Varlinskaya, Elena I; Truxell, Eric; Spear, Linda P

    2014-08-01

    This study assessed long-lasting consequences of repeated ethanol exposure during two different periods of adolescence on 1) baseline levels of social investigation, play fighting, and social preference and 2) sensitivity to the social consequences of acute ethanol challenge. Adult male and female Sprague-Dawley rats were tested 25 days after repeated exposure to ethanol (3.5 g/kg intragastrically [i.g.], every other day for a total of 11 exposures) in a modified social interaction test. Early-mid adolescent intermittent exposure (e-AIE) occurred between postnatal days (P) 25 and 45, whereas late adolescent intermittent exposure (l-AIE) was conducted between P45 and P65. Significant decreases in social investigation and social preference were evident in adult male rats, but not their female counterparts following e-AIE, whereas neither males nor females demonstrated these alterations following l-AIE. In contrast, both e-AIE and l-AIE produced alterations in sensitivity to acute ethanol challenge in males tested 25 days after adolescent exposure. Ethanol-induced facilitation of social investigation and play fighting, reminiscent of that normally seen during adolescence, was evident in adult males after e-AIE, whereas control males showed an age-typical inhibition of social behavior. Males after l-AIE were found to be insensitive to the socially suppressing effects of acute ethanol challenge, suggesting the development of chronic tolerance in these animals. In contrast, females showed little evidence for alterations in sensitivity to acute ethanol challenge following either early or late AIE. The results of the present study demonstrate a particular vulnerability of young adolescent males to long-lasting detrimental effects of repeated ethanol. Retention of adolescent-typical sensitivity to the socially facilitating effects of ethanol could potentially make ethanol especially appealing to these males, therefore promoting relatively high levels of ethanol intake later

  2. Identity Abuse as a Tactic of Violence in LGBTQ Communities: Initial Validation of the Identity Abuse Measure.

    PubMed

    Woulfe, Julie M; Goodman, Lisa A

    2018-03-01

    Intimate partner violence (IPV; i.e., physical, sexual, or psychological abuse by a current or former partner) remains a public health concern with devastating personal and societal costs. Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals are also vulnerable to a dimension of IPV called identity abuse (IA); that is, abuse tactics that leverage systemic oppression to harm an individual. Yet, we know little about its relative prevalence in subgroups of the LGBTQ community. This study developed and evaluated a measure of IA, and explored its prevalence in a sample of 734 sexual minority adults. The sample included women (53.1%), men (27.4%), and transgender or gender nonconforming "TGNC" (19.3%) participants. The majority of participants identified as queer or pansexual (38.7%), then gay (23.6%), lesbian (22.8%), and bisexual (13.6%). Participants completed an online survey that included measures of IA and physical, sexual, and psychological abuse. The IA items formed a unidimensional factor structure with strong internal consistency and construct validity. Nearly one fifth of the sample (16.8%) experienced past year IA and 40.1% reported adult IA. Women experienced greater exposure to IA in adulthood than men, and TGNC participants reported higher rates of IA in adulthood and in the last year compared to their cisgender counterparts. The odds of queer or bisexual participants reporting IA in adulthood were almost three times higher than gay participants, and two times higher than lesbian participants. Findings have implications for advancing assessment of partner abuse in the LGBTQ community, LGBTQ-competent clinical care, and training of practitioners.

  3. The Educator's Guide to Preventing Child Sexual Abuse.

    ERIC Educational Resources Information Center

    Nelson, Mary, Ed.; Clark, Kay, Ed.

    This collection of articles was created to give professionals and educators an informed overview of current issues in the field of child sexual abuse prevention. Articles are grouped under the headings of Introduction, Issues in Child Sexual Abuse Prevention, and Guidelines for Prevention Education and include: (1) "Prevention Education in…

  4. STOP Abusive Behavior Syndrome: Developing a Community Response.

    ERIC Educational Resources Information Center

    Holzman, Lois; Rivera, Mary

    This paper discusses the social-therapeutic approach to preventing abusive behavior, and describes the implementation of specific STOP Abusive Behavior Syndrome (ABS) projects in New York City, New York. The projects' goal is to empower people to continually develop throughout their lifespans. Basic tenants include the following: (1) emotions are…

  5. Internet Abuse and Internet Addiction in the Workplace

    ERIC Educational Resources Information Center

    Griffiths, Mark

    2010-01-01

    Purpose: This paper seeks to overview the issues, concerns and challenges relating to internet abuse and internet addiction in the workplace. Design/methodology/approach: Using psychological literature, the paper outlines a number of important and inter-related areas including brief overviews of internet abuse, and the most extreme form of…

  6. Thermodynamics of R-(+)-2-(4-Hydroxyphenoxy)propanoic Acid Dissolution in Methanol, Ethanol, and Methanol-Ethanol Mixture

    NASA Astrophysics Data System (ADS)

    Liu, Wei; Ma, Jinju; Yao, Xinding; Fang, Ruina; Cheng, Liang

    2018-05-01

    The solubilities of R-(+)-2-(4-hydroxyphenoxy)propanoic acid (D-HPPA) in methanol, ethanol and various methanol-ethanol mixtures are determined in the temperature range from 273.15 to 323.15 K at atmospheric pressure using a laser detecting system. The solubilities of D-HPPA increase with increasing mole fraction of ethanol in the methanol-ethanol mixtures. Experimental data were correlated with Buchowski-Ksiazczak λ h equation and modified Apelblat equation; the first one gives better approximation for the experimental results. The enthalpy, entropy and Gibbs free energy of D-HPPA dissolution in methanol, ethanol and methanol-ethanol mixtures were also calculated from the solubility data.

  7. The effect of childhood abuse on the risk of adult obesity.

    PubMed

    Wang, Yue; Wu, Bo; Yang, Helen; Song, Xiaoyi

    2015-08-01

    The purpose of this study was to assess the association between childhood abuse and adult obesity. We performed a comprehensive meta-analysis, which included studies that reported odds ratio (OR) estimates with 95% confidence intervals (CI). Summary estimates of association were obtained using a random-effects model. Heterogeneity among studies was evaluated using Cochran Q and I2 statistics. A total of 22 cohort studies (3 prospective, 19 retrospective) were included in this meta-analysis. The pooled OR was 1.23 (95% CI, 1.16-1.31). All 4 subcategories of abuse were associated with adult obesity: physical abuse (OR, 1.26; 95% CI, 1.10-1.42), psychological abuse (OR, 1.20; 95% CI, 1.07-1.33), sexual abuse (OR, 1.22; 95% CI, 1.05-1.38), and neglect (OR, 1.22; 95% CI, 1.12-1.32). Moreover, dose-response analysis showed that severe abuse (OR, 1.38; 95% CI, 1.14-1.1.62) was significantly associated with adult obesity compared with light/moderate abuse (OR, 1.01; 95% CI, 0.84-1.18). Although slight publication bias was observed (Egger test P = .05), effect sizes remained statistically significant in sensitivity analyses. This research demonstrated a remarkably consistent association between childhood abuse and adult obesity. Medical practitioners need to be aware of the important role of childhood abuse in the development of obesity.

  8. Thermophilic ethanol fermentation from lignocellulose hydrolysate by genetically engineered Moorella thermoacetica.

    PubMed

    Rahayu, Farida; Kawai, Yuto; Iwasaki, Yuki; Yoshida, Koichiro; Kita, Akihisa; Tajima, Takahisa; Kato, Junichi; Murakami, Katsuji; Hoshino, Tamotsu; Nakashimada, Yutaka

    2017-12-01

    A transformant of Moorella thermoacetica was constructed for thermophilic ethanol production from lignocellulosic biomass by deleting two phosphotransacetylase genes, pdul1 and pdul2, and introducing the native aldehyde dehydrogenase gene (aldh) controlled by the promoter from glyceraldehyde-3-phosphate dehydrogenase. The transformant showed tolerance to 540mM and fermented sugars including fructose, glucose, galactose and xylose to mainly ethanol. In a mixed-sugar medium of glucose and xylose, all of the sugars were consumed to produce ethanol at the yield of 1.9mol/mol-sugar. The transformant successfully fermented sugars in hydrolysate prepared through the acid hydrolysis of lignocellulose to ethanol, suggesting that this transformant can be used to ferment the sugars in lignocellulosic biomass for ethanol production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Repeated episodes of chronic intermittent ethanol promote insensitivity to devaluation of the reinforcing effect of ethanol

    PubMed Central

    Lopez, M. F.; Becker, H. C.; Chandler, L. J.

    2014-01-01

    Studies in animal models have shown that repeated episodes of alcohol dependence and withdrawal promote escalation of drinking that is presumably associated with alterations in the addiction neurocircuitry. Using a lithium chloride-ethanol pairing procedure to devalue the reinforcing properties of ethanol, the present study determined whether multiple cycles of chronic intermittent ethanol (CIE) exposure by vapor inhalation also alters the sensitivity of drinking behavior to the devaluation of ethanol's reinforcing effects. The effect of devaluation on operant ethanol self-administration and extinction was examined in mice prior to initiation of CIE (short drinking history) and after repeated cycles of CIE or air control exposure (long drinking history). Devaluation significantly attenuated the recovery of baseline ethanol self-administration when tested either prior to CIE or in the air-exposed controls that had experienced repeated bouts of drinking but no CIE. In contrast, in mice that had undergone repeated cycles of CIE exposure that promoted escalation of ethanol drinking, self-administration was completely resistant to the effect of devaluation. Devaluation had no effect on the time course of extinction training in either pre-CIE or post-CIE mice. Taken together, these results are consistent with the suggestion that repeated cycles of ethanol dependence and withdrawal produce escalation of ethanol self-administration that is associated with a change in sensitivity to devaluation of the reinforcing properties of ethanol. PMID:25266936

  10. Understanding economic abuse in the lives of survivors.

    PubMed

    Postmus, Judy L; Plummer, Sara-Beth; McMahon, Sarah; Murshid, N Shaanta; Kim, Mi Sung

    2012-02-01

    Intimate partner violence (IPV) often includes economic abuse as one tactic commonly used by an abuser; unfortunately, there is a lack of empirical understanding of economic abuse. Additionally, research is limited on the predictors of economic self-sufficiency in the lives of women experiencing IPV. This paper furthers our knowledge about economic abuse and its relationship with economic self-sufficiency by presenting the results from an exploratory study with IPV survivors participating in a financial literacy program. Of the 120 individuals who participated in the first wave, 94% experienced some form of economic abuse, which also correlated highly with other forms of IPV. Seventy-nine percent experienced some form of economic control, 79% experienced economic exploitative behaviors, and 78% experienced employment sabotage. MANOVA results also indicated that economic control differed significantly based on education with those with a high school education experiencing higher rates than those with less than high school education or those with some college. Finally, results from the OLS regressions indicated that experiencing any form of economic abuse as well as economic control significantly predicted a decrease in economic self sufficiency. Implications suggest that advocates should assess for economic abuse when working with survivors and should be prepared to offer financial tools to increase survivors' economic self-sufficiency. Policymakers should understand the ramifications of economic abuse and create policies that support survivors and prohibit economic abuse. Finally, more research is needed to fully understand economic abuse and its impact on survivors and their economic self-sufficiency.

  11. Alienation and Domestic Abuse: How Abused Women Cope with Loneliness

    ERIC Educational Resources Information Center

    Arokach, Ami

    2006-01-01

    This study explored the manner in which abused women cope with loneliness. Eighty women, victims of domestic abuse, were compared to 84 women from the general population who have had no history of abusive relationships. A 34-item yes/no loneliness questionnaire was utilized in order to compare the "beneficial" ways of coping with loneliness in the…

  12. [Prevalence of sexual abuse in students and its relation with drug abuse].

    PubMed

    Ramos-Lira, L; Saldívar-Hernández, G; Medina-Mora, M E; Rojas-Guiot, E; Villatoro-Velázquez, J

    1998-01-01

    To determine the prevalence of sexual abuse among high school (secondary and preparatory) students, male and female, throughout Mexico, and its relationship with drug abuse. Data were obtained from the National Survey of Drug Use in Schools applied in November and December, 1991. A total of 61,779 students, 51.8% men and 47.1% women, with a mean age of 14.4 years completed the self-applied questionnaire. Sexual abuse was explored from the perspective of the abusers and of the victims. The prevalence of sexual abuse in adolescent victims was 4.3% and no statistically significant differences were found between sexes. The prevalence of sexual aggressors was 2.5%. Men coerced someone else in a higher proportion than women. Adolescent women experienced sexual abuse at a younger age than men and they also reported a higher percentage of intrafamily abuse. Men reported friends as the most frequent aggressors. Victims and aggressors of both sexes reported a significantly higher drug consumption than students without these antecedents. The differences in the experience of sexual abuse between men and women are described. In particular, the fact that sexual abuse in men mainly occurs outside the family sphere, while in women it is mainly within the family and at a younger age than in men. Additionally, the need for further research focusing on the consequences on mental health of infantile and adolescent sexual abuse and drug consumption is emphasized, considering the characteristics of each gender.

  13. Elder Abuse among African Americans

    ERIC Educational Resources Information Center

    Tauriac, Jesse J.; Scruggs, Natoschia

    2006-01-01

    Perceptions of extreme, moderate, and mild forms of elder abuse among African-American women (n=25) and men (n=10) were examined. African-American respondents emphasized physical abuse when giving examples of extremely abusive behavior. Along with physical abuse, verbal abuse was the most frequently identified form of abuse, and was significantly…

  14. Predictors of ethanol consumption in adult Sprague-Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake.

    PubMed

    Karatayev, Olga; Barson, Jessica R; Carr, Ambrose J; Baylan, Jessica; Chen, Yu-Wei; Leibowitz, Sarah F

    2010-06-01

    To investigate mechanisms in outbred animals that increase the propensity to consume ethanol, it is important to identify and characterize these animals before or at early stages in their exposure to ethanol. In the present study, different measures were examined in adult Sprague-Dawley rats to determine whether they can predict long-term propensity to overconsume ethanol. Before consuming 9% ethanol with a two-bottle choice paradigm, rats were examined with the commonly used behavioral measures of novelty-induced locomotor activity and anxiety, as assessed during 15 min in an open-field activity chamber. Two additional measures, intake of a low 2% ethanol concentration or circulating triglyceride (TG) levels after a meal, were also examined with respect to their ability to predict chronic 9% ethanol consumption. The results revealed significant positive correlations across individual rats between the amount of 9% ethanol ultimately consumed and three of these different measures, with high scores for activity, 2% ethanol intake, and TGs identifying rats that consume 150% more ethanol than rats with low scores. Measurements of hypothalamic peptides that stimulate ethanol intake suggest that they contribute early to the greater ethanol consumption predicted by these high scores. Rats with high 2% ethanol intake or high TGs, two measures found to be closely related, had significantly elevated expression of enkephalin (ENK) and galanin (GAL) in the hypothalamic paraventricular nucleus (PVN) but no change in neuropeptide Y (NPY) in the arcuate nucleus (ARC). This is in contrast to rats with high activity scores, which in addition to elevated PVN ENK expression showed enhanced NPY in the ARC but no change in GAL. Elevated ENK is a common characteristic related to all three predictors of chronic ethanol intake, whereas the other peptides differentiate these predictors, with GAL enhanced with high 2% ethanol intake and TG measures but NPY related to activity. 2010 Elsevier

  15. Human abuse liability evaluation of CNS stimulant drugs.

    PubMed

    Romach, Myroslava K; Schoedel, Kerri A; Sellers, Edward M

    2014-12-01

    Psychoactive drugs that increase alertness, attention and concentration and energy, while also elevating mood, heart rate and blood pressure are referred to as stimulants. Despite some overlapping similarities, stimulants cannot be easily categorized by their chemical structure, mechanism of action, receptor binding profile, effects on monoamine uptake, behavioral pharmacology (e.g., effects on locomotion, temperature, and blood pressure), therapeutic indication or efficacy. Because of their abuse liability, a pre-market assessment of abuse potential is required for drugs that show stimulant properties; this review article focuses on the clinical aspects of this evaluation. This includes clinical trial adverse events, evidence of diversion or tampering, overdoses and the results of a human abuse potential study. While there are different types of human experimental studies that can be employed to evaluate stimulant abuse potential (e.g., drug discrimination, self-administration), only the human abuse potential study and clinical trial adverse event data are required for drug approval. The principal advances that have improved human abuse potential studies include using study enrichment strategies (pharmacologic qualification), larger sample sizes, better selection of endpoints and measurement strategies and more carefully considered interpretation of data. Because of the methodological advances, comparisons of newer studies with historical data is problematic and may contribute to a biased regulatory framework for the evaluation of newer stimulant-like drugs, such as A2 antagonists. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Substance Abuse among Drivers of Motor Vehicle Collisions

    PubMed Central

    Derakhshanfar, Hojjat; Kalantari Meibodi, Mohamad; Kariman, Hamid; Arhamidolatabadi, Ali; Safari, Saeed

    2012-01-01

    Background: Motor vehicle collisions (MVC) comprise a majority cause of referral to the emergency department (ED). A large proportion of MVC appear to be preventable, if more effective measures against driving after substance abuse can be implemented. Objective: This study was aimed to investigate the prevalence of substance abuse among drivers of MVC, following road traffic accidents (RTA). Materials and Methods: This case-control research was conducted from July to October 2007. One hundred MVC drivers admitted in the ED were included as the case group and 110 hospitalized patients, due to nontraumatic causes were used as controls. History of substances abused was obtained and urine samples were tested for opium in both groups. Finally the history and laboratory results of the groups were compared using SPSS 18. Results: Of the 100 patients in the case group, 39 (39%) were positive for substance abuse (100% males). On the other hand, 49 (44.5%) patients in the control group had positive history or laboratory findings of substance abuse (73.9% male). Opioids were the most common agent abused in both groups. There was no significant difference between two groups regarding the prevalence of substance abuse (P = 0.92). Conclusions: The prevalence of substance abuse is high among victims of road traffic injury but in equal proportion to the control group. Health education and counseling is needed to reduce substance abuse in the general population although it was not significantly related to the cause of RTA. PMID:24829889

  17. Abuse history and premenstrual symptomatology: assessing the mediating role of perceived stress.

    PubMed

    Lustyk, M Kathleen B; Widman, Laura; Becker, Linda de Laveaga

    2007-01-01

    The present study assessed the interrelationships among abuse history (Abuse), perceived stress (Stress), and premenstrual symptom severity reports (PMSR) among female college students (N = 91, 18-25 years old), and determined if Stress mediated the relationship between Abuse and PMSR. Abuse history was noted by 44% of women in this sample, including sexual (25%), physical (11%), or both sexual and physical (8%) abuse. Importantly, results showed significant positive relationships between Abuse, Stress, and PMSR, suggesting Abuse affects psychological and physical aspects of women's health. Overall, women rated PMSR affect symptoms highest, and abused women rated pain and water retention higher than non-abused women. Stress did not fully mediate the relationship between Abuse and PMSR in this study, but accounted for 24% of the variance between these variables. The health implications of these findings are discussed.

  18. Childhood sexual abuse and substance abuse treatment utilization among substance-dependent incarcerated women.

    PubMed

    Peltan, Jessica R; Cellucci, Tony

    2011-10-01

    Incarcerated women have high rates of substance abuse problems and trauma. A variety of variables may influence whether these women seek help or are referred for substance abuse problems. This study reports an exploratory project on service utilization among incarcerated substance-dependent women (N = 40) in southeastern Idaho. Using self-report and interview tools, most participants reported some substance abuse treatment history, although extent and types of treatment varied. Most of the women also reported some type of childhood abuse. Age, income, and consequences of alcohol and other drug use related positively to substance abuse treatment. However, severity of childhood sexual abuse and current trauma symptoms were negatively correlated with substance abuse treatment episodes. These women may use substances to cope with childhood trauma or may not perceive the substance abuse system as responsive to their co-occurring trauma symptoms. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. [Legal consequences in cases of child abuse].

    PubMed

    Clauß, D; Richter, C; Klohs, G; Heide, S

    2013-09-01

    Medical child protection includes besides interdisciplinary diagnostics and treatment of physical and psychological symptoms also a discussion that looks at the ensuing legal consequences.This study analyses 21 criminally investigated cases of suspected child abuse from a 2 year study period and compares severity of injury to legal outcome.7 of those 21 criminal proceedings were already dropped by the prosecution and never went to trial. 4 of the 8 cases that led to a trial ended with a conviction. In all of the 4 cases that resulted in an acquittal the judges had been convinced that the child had been abused but found themselves unable to exactly identify the perpetrator. Our study's cases did not show a positive correlation between severity of injury and legal outcome.Diagnosing and treating children and minors within the context of medical child protection should always also include the ques-tion of possible legal consequences. The judicial process in cases of serious child abuse requires high medical expertise. Such expertise particularly includes the ability to determine the time of injury as exactly as possible and to provide precise written documentation of any medical findings. However, our study also shows that medical assessment is only one of many aspects in the legal response to child abuse. © Georg Thieme Verlag KG Stuttgart · New York.

  20. A Theoretical Foundation for Understanding Clergy-Perpetrated Sexual Abuse

    ERIC Educational Resources Information Center

    Fogler, Jason M.; Shipherd, Jillian C.; Rowe, Erin; Jensen, Jennifer; Clarke, Stephanie

    2008-01-01

    Incorporating elements from broadband theories of psychological adaptation to extreme adversity, including Summit's (1983) Child Sexual Abuse Accommodation Syndrome, Finkelhor and Browne's (1986) Traumagenic Dynamics Model of sexual abuse, and Pyszczynski and colleagues' (1997) Terror Management Theory, this paper proposes a unified theoretical…

  1. Study on the micro direct ethanol fuel cell (Micro-DEFC) performance

    NASA Astrophysics Data System (ADS)

    Saisirirat, Penyarat; Joommanee, Bordindech

    2018-01-01

    The direct ethanol fuel cell (DEFC) is selected for this research. DEFC uses ethanol in the fuel cell instead of the more toxic methanol. Ethanol is more attractive than methanol by many reasons. Ethanol is a hydrogen-rich liquid and it has a higher specific energy (8.0 kWh/kg) compared to that of methanol (6.1 kWh/kg). Ethanol can be obtained in great quantity from biomass through a fermentation process from renewable resources such as sugar cane, wheat, corn, and even straw. The use of ethanol would also overcome both the storage and infrastructure challenge of hydrogen for fuel cell applications. The experimental apparatus on the micro direct ethanol fuel cell for measuring the cell performance has been set for this research. The objective is to study the micro direct ethanol fuel cell performance for applying with the portable electronic devices. The cell performance is specified in the terms of cell voltage, cell current and power of the cell at room operating temperature and 1 atm for the pressure and also includes the ethanol fuel consumption. The effect of operating temperature change on the electrical production performance is also studied. The steady-state time for collecting each data value is about 5-10 minutes. The results show that with the increase of concentrations of ethanol by volume, the reactant concentration at the reaction sites increases so the electrochemical rate also increases but when it reaches the saturated point the performance gradually drops.

  2. Combined use of fatty acid ethyl esters and ethyl glucuronide in hair for diagnosis of alcohol abuse: interpretation and advantages.

    PubMed

    Pragst, F; Rothe, M; Moench, B; Hastedt, M; Herre, S; Simmert, D

    2010-03-20

    In this study the combined use of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) for diagnoses of chronically excessive alcohol abuse is investigated at 174 hair samples from driving ability examination, workplace testing and child custody cases for family courts and evaluated with respect to the basics of interpretation. Using the cut-off values of 0.50 ng/mg for FAEE and 25 pg/mg for EtG, both markers were in agreement in 75% of the cases with 103 negative and 28 positive results and there were 30 cases with FAEE positive and EtG negative and 13 cases with FAEE negative and EtG positive. As the theoretical basis of interpretation, the pharmacokinetics of FAEE and EtG is reviewed for all steps between drinking of ethanol to incorporation in hair with particular attention to relationships between alcohol dose and concentrations in hair. It is shown that the concentrations of both markers are essentially determined by the area under the ethanol concentration in blood vs. time curve AUC(EtOH), despite large inter-individual variations. It is demonstrated by calculation of AUC(EtOH) on monthly basis for moderate, risky and heavy drinking that AUC(EtOH) increases very strongly in the range between 60 and 120 g ethanol per day. This specific feature which is caused by the zero-order elimination of ethanol is a favorable prerequisite for a high discrimination power of the hair testing for alcohol abuse. From the consideration of the different profiles of FAEE and EtG along the hair and in agreement with the literature survey, a standardized hair segment 0-3 cm is proposed with cut-off values of 0.5 ng/mg for FAEE and 30 pg/mg for EtG. This improves also the agreement between FAEE and EtG results in the cases of the present study. A scheme for combined interpretation of FAEE and EtG is proposed which uses the levels of abstinence and the double of the cut-off values as criteria in addition to the cut-off's. Considering the large variations in the relationship

  3. Verbal abuse, like physical and sexual abuse, in childhood is associated with an earlier onset and more difficult course of bipolar disorder.

    PubMed

    Post, Robert M; Altshuler, Lori L; Kupka, Ralph; McElroy, Susan L; Frye, Mark A; Rowe, Michael; Leverich, Gabriele S; Grunze, Heinz; Suppes, Trisha; Keck, Paul E; Nolen, Willem A

    2015-05-01

    Physical or sexual abuse in childhood is known to have an adverse effect on the course of bipolar disorder, but the impact of verbal abuse has not been well elucidated. We examined the occurrence and frequency (never to frequently) of each type of abuse in childhood in 634 US adult outpatients (average age 40 years). Patients gave informed consent and provided information about their age of onset and course of illness prior to study entry. Verbal abuse alone occurred in 24% of the patients. Similar to a history of physical or sexual abuse, a history of verbal abuse was related to an earlier age of onset of bipolar disorder and other poor prognosis characteristics, including anxiety and substance abuse comorbidity, rapid cycling, and a deteriorating illness course as reflected in ratings of increasing frequency or severity of mania and depression. A lasting adverse impact of the experience of verbal abuse in childhood is suggested by its relationship to an earlier age of onset of bipolar disorder, other poor prognosis factors, and a deteriorating course of illness. Verbal abuse is a common confound in comparison groups defined by a lack of physical or sexual abuse. Ameliorating the impact of verbal abuse on the unfolding course of bipolar disorder appears to be an important target of therapeutics and worthy of attempts at primary and secondary prophylaxis. Family-based treatments that focus on psychoeducation, enhancing intra-family communication, and coping skills may be particularly helpful. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Drug and Substance Abuse

    MedlinePlus

    ... Some older adults also abuse illegal drugs, including marijuana, cocaine, hallucinogens, and injected narcotics. Some people misuse more than one substance. Many older adults who become addicted to drugs also have another serious medical condition, such as chronic pain or a mental ...

  5. Ethanol, saccharin, and quinine: early ontogeny of taste responsiveness and intake.

    PubMed

    Kozlov, Andrey P; Varlinskaya, Elena I; Spear, Norman E

    2008-02-01

    Rat pups demonstrate high levels of immediate acceptance of ethanol during the first 2 weeks of postnatal life. Given that the taste of ethanol is most likely perceived by infant rats as a combination of sweet and bitter, high intake of ethanol early in ontogeny may be associated with age-related enhanced responsiveness to the sweet component of ethanol taste, as well as with ontogenetic decreases in sensitivity to its bitter component. Therefore, the present study compared responsiveness to ethanol and solutions with bitter (quinine) and sweet (saccharin) taste in terms of intake and palatability across the first 2 weeks of postnatal life. Characteristic patterns of responsiveness to 10% (v/v) ethanol, 0.1% saccharin, 0.2% quinine, and water in terms of taste reactivity and fluid intake were assessed in rat pups tested on postnatal day (P) 4, 9, or 12 using a new technique of on-line monitoring of fluid flow through a two-channel intraoral cannula. Taste reactivity included analysis of ingestive and aversive responses following six intraoral infusions of the test fluids. This taste reactivity probe was followed by the intake test, in which animals were allowed to voluntarily ingest fluids from an intraoral cannula. Pups of all ages showed more appetitive responses to saccharin and ethanol than to water or quinine. No age-related differences were apparent in taste responsiveness to saccharin and ethanol. However, the age-related pattern of ethanol intake drastically differed from that of saccharin. Intake of saccharin increased from P4 to P9 and decreased substantially by P12, whereas intake of ethanol gradually increased from P4 to P12. Intake of ethanol was significantly lower than intake of saccharin on P9, whereas P12 pups took in more ethanol than saccharin. The findings of the present study indicate ontogenetic dissociations between taste reactivity to ethanol and saccharin and intake of these solutions, and suggest that high acceptance of ethanol early in

  6. Intimate Partner Violence and Cigarette Smoking: Association Between Smoking Risk and Psychological Abuse With and Without Co-Occurrence of Physical and Sexual Abuse

    PubMed Central

    Jun, Hee-Jin; Rich-Edwards, Janet W.; Boynton-Jarrett, Renée; Wright, Rosalind J.

    2008-01-01

    Objectives. We examined the association between psychological abuse in a current relationship and current cigarette smoking among women, with and without the co-occurrence of physical or sexual abuse. Methods. Women’s experience of psychological abuse, experience of physical or sexual abuse, and smoking status were ascertained through a survey of female nurses. A score of 20 or more on the Women’s Experience With Battering scale defined psychological abuse. We used logistic regression to predict current smoking, adjusting for demographic and social covariates. Analyses included women in a current relationship (n=54200). Results. Adjusted analyses demonstrated that women experiencing only psychological abuse alone were 33% (95% confidence interval [CI]=13%, 57%) more likely to smoke than nonabused women. Compared with nonabused women, psychologically abused women’s risk of smoking was greater if they reported a single co-occurrence of physical or sexual abuse (odds ratio [OR]=1.5; 95% CI=1.3, 1.8) or multiple co-occurrences (OR=1.9; 95% CI=1.7, 2.3). Conclusions. Psychological abuse in a current relationship was associated with an increased risk of smoking in this cohort of largely White, well-educated, and employed women. The co-occurrence of physical or sexual abuse enhanced that risk. Further research is needed to see if these associations hold for other groups. PMID:17600272

  7. Community characteristics associated with child abuse in Iowa.

    PubMed

    Weissman, Alicia M; Jogerst, Gerald J; Dawson, Jeffrey D

    2003-10-01

    Various demographic and community characteristics are associated with child abuse rates in national and urban samples, but similar analyses have not been done within rural areas. This study analyzes the relationships between reported and substantiated rates of child abuse and county demographic, health care resource and social services factors in a predominantly rural state in the US. County-level data from Iowa between 1984-1993 were analyzed for associations between county characteristics and rates of child abuse using univariate correlations and multivariate stagewise regression analysis. Population-adjusted rates of reported and substantiated child abuse were correlated with rates of children in poverty, single-parent families, marriage and divorce, unemployment, high-school dropouts, median family income, elder abuse, birth and death rates, numbers of physicians and other healthcare providers, hospital, social workers, and number of caseworkers in the Department of Human Services. Rates of single-parent families, divorce and elder abuse were significantly associated with reported and substantiated child abuse in multivariate analysis, while economic and most health care factors were not. Reporting and substantiation rates differed across districts after adjustment for multiple factors including caseworker workload. In this rural state, family structure is more significantly associated with child abuse report and substantiation rates than are socioeconomic factors. The level of health care resources in a county does not appear to affect these rates.

  8. Fermentation method producing ethanol

    DOEpatents

    Wang, Daniel I. C.; Dalal, Rajen

    1986-01-01

    Ethanol is the major end product of an anaerobic, thermophilic fermentation process using a mutant strain of bacterium Clostridium thermosaccharolyticum. This organism is capable of converting hexose and pentose carbohydrates to ethanol, acetic and lactic acids. Mutants of Clostridium thermosaccharolyticum are capable of converting these substrates to ethanol in exceptionally high yield and with increased productivity. Both the mutant organism and the technique for its isolation are provided.

  9. Domestic elder abuse in Yazd, Iran: a cross-sectional study.

    PubMed

    Morowatisharifabad, Mohammad Ali; Rezaeipandari, Hassan; Dehghani, Ali; Zeinali, Ahmad

    2016-01-01

    Social changes due to urbanism, acculturation, and fading of values have led to some challenges in family relationships, including domestic elder abuse. This study was conducted to determine elder abuse status in Yazd, Iran. This cross-sectional study was conducted on 250 elderly people over 60 years in Yazd in 2014-2015. Clustered random sampling was used to recruit the participants from 10 clusters in Yazd (25 individuals from each cluster). The data were gathered by the 49-item,Iranian Domestic Elder Abuse Questionnaire which was filled out through private interviews with the participants. Mean score of elder abuse was 11.84 (SD: 12.70) of total 100. Of the participants,79.6% (95% CI: 74.5-84.6) experienced at least one type of abuse. Emotional neglect was the most reported abuse and physical abuse was the least reported. Abuse score was associated with age, education level, living status, and insurance status of elders. Further, those who reported history of gastrointestinal problems, dyslipidemia, respiratory diseases, sleep disorders, audiovisual problems, joints pain, hypertension, dental/oral problems, cardiovascular disease,urinary incontinence and disability, reported a statistically significant higher abuse score. Despite overall low rate of domestic elder abuse, its high prevalence indicates that some interventions are necessary to decrease domestic elder abuse. Emotional neglect of elders should be addressed more than other abuse types.

  10. Domestic elder abuse in Yazd, Iran: a cross-sectional study

    PubMed Central

    Morowatisharifabad, Mohammad Ali; Rezaeipandari, Hassan; Dehghani, Ali; Zeinali, Ahmad

    2016-01-01

    Background: Social changes due to urbanism, acculturation, and fading of values have led to some challenges in family relationships, including domestic elder abuse. This study was conducted to determine elder abuse status in Yazd, Iran. Methods: This cross-sectional study was conducted on 250 elderly people over 60 years in Yazd in 2014-2015. Clustered random sampling was used to recruit the participants from 10 clusters in Yazd (25 individuals from each cluster). The data were gathered by the 49-item,Iranian Domestic Elder Abuse Questionnaire which was filled out through private interviews with the participants. Results: Mean score of elder abuse was 11.84 (SD: 12.70) of total 100. Of the participants,79.6% (95% CI: 74.5-84.6) experienced at least one type of abuse. Emotional neglect was the most reported abuse and physical abuse was the least reported. Abuse score was associated with age, education level, living status, and insurance status of elders. Further, those who reported history of gastrointestinal problems, dyslipidemia, respiratory diseases, sleep disorders, audiovisual problems, joints pain, hypertension, dental/oral problems, cardiovascular disease,urinary incontinence and disability, reported a statistically significant higher abuse score. Conclusion: Despite overall low rate of domestic elder abuse, its high prevalence indicates that some interventions are necessary to decrease domestic elder abuse. Emotional neglect of elders should be addressed more than other abuse types. PMID:27386426

  11. Acute and chronic ethanol intake: effects on spatial and non-spatial memory in rats.

    PubMed

    García-Moreno, Luis M; Cimadevilla, Jose M

    2012-12-01

    Abusive alcohol consumption produces neuronal damage and biochemical alterations in the mammal brain followed by cognitive disturbances. In this work rats receiving chronic and acute alcohol intake were evaluated in a spontaneous delayed non-matching to sample/position test. Chronic alcohol-treated rats had free access to an aqueous ethanol solution as the only available liquid source from the postnatal day 21 to the end of experiment (postnatal day 90). Acute alcoholic animals received an injection of 2 g/kg ethanol solution once per week. Subjects were evaluated in two tests (object recognition and spatial recognition) based on the spontaneous delayed non-matching to sample or to position paradigm using delays of 1 min, 15 min and 60 min. Results showed that chronic and acute alcohol intake impairs the rats' performance in both tests. Moreover, chronic alcohol-treated rats were more altered than acute treated animals in both tasks. Our results support the idea that chronic and acute alcohol administration during postnatal development caused widespread brain damage resulting in behavioral disturbances and learning disabilities. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Conflicts between motivational systems related to attachment trauma: Key to understanding the intra-family relationship between abused children and their abusers.

    PubMed

    Liotti, Giovanni

    2017-01-01

    Research on disorganization of infant attachment provides evidence that it can be caused not only by violent aggression or very early sexual abuse, but also by covert maltreating behavior, which includes the abdication of the caregiver's responsibility to soothe the infant's distress. This paper argues that both overtly abusive caregivers and merely "abdicating" caregivers may cause disorganization of infant attachment through a simultaneous and conflicting activation of the motivational systems governing attachment and survival defense in the infant. Other inborn motivational systems-regulating caretaking, competitiveness, and sexuality-are disorderly activated, during personality development, within the intra-family relationships of children whose infant attachment has been disorganized. The paper argues that conflicts and abnormal tensions between different motivational systems explain some paradoxical features of the interactions between abusers and abused, and allow for a better understanding of the interpersonal processes involved in the surfacing and exacerbation of dissociative symptoms in the abused.

  13. 76 FR 65517 - National Institute on Drug Abuse Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-21

    ... individual intramural programs and projects conducted by the National Institute on Drug Abuse, including.... Place: Intramural Research Program, National Institute on Drug Abuse, NIH, Johns Hopkins Bayview Campus..., Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, 251 Bayview Boulevard, Baltimore...

  14. 78 FR 55265 - National Institute on Drug Abuse; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-10

    ... individual intramural programs and projects conducted by the National Institute on Drug Abuse, including.... Place: Intramural Research Program, National Institute on Drug Abuse, NIH, Johns Hopkins Bayview Campus..., Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, 251 Bayview Boulevard, Baltimore...

  15. EFFECTS OF ETHANOL EXPOSURE DURING ADOLESCENCE OR IN ADULTHOOD ON PAVLOVIAN CONDITIONED APPROACH IN SPRAGUE-DAWLEY RATS

    PubMed Central

    McClory, Alexander James; Spear, Linda

    2014-01-01

    Human studies have shown that adolescents who repeatedly use alcohol are more likely to be dependent on alcohol and are more likely to suffer from psychological problems later in life. There has been limited research examining how ethanol exposure in adolescence might contribute to later abuse or addiction in adulthood. The present experiment examined effects of intermittent ethanol exposure during adolescence on sign-tracking behavior in adulthood, indexed by a Pavlovian conditioned approach (PCA) task wherein an 8-s lever presentation served as a cue predicting subsequent delivery of a flavored food pellet. Although no response was required for food delivery, after multiple pairings, 1 of 2 different responses often emerged during the lever presentation: goal tracking (head entries into the food trough) or sign tracking (engagement with the lever when presented). Sign tracking is thought to reflect the attribution of incentive salience to reward-paired cues and has been previously correlated with addiction-like behaviors. Following the last PCA session, blood samples were collected for analysis of post-session corticosterone levels. Sixty-two rats (n = 10–12/group) were pseudo-randomly assigned to 1 of 2 intragastric (i.g.) exposure groups (water or 4 g/kg ethanol) or a non-manipulated (NM) control group. Animals were intubated with ethanol or water every other session from postnatal session (PND) 28–48 or PND 70–90. Rats were then tested in adulthood (PND 71–79 or PND 113–122) on the PCA task. Animals exposed chronically to ethanol during adolescence exhibited significantly higher levels of sign-tracking behavior in adulthood than NM and water-treated animals, and showed higher corticosterone than NM control animals. These effects were not seen after comparable ethanol exposure in adulthood. These results suggest that adolescent alcohol exposure has long-term consequences on the expression of potential addiction-relevant behaviors in adulthood. PMID

  16. Effects of ethanol exposure during adolescence or in adulthood on Pavlovian conditioned approach in Sprague-Dawley rats.

    PubMed

    McClory, Alexander James; Spear, Linda Patia

    2014-12-01

    Human studies have shown that adolescents who repeatedly use alcohol are more likely to be dependent on alcohol and are more likely to suffer from psychological problems later in life. There has been limited research examining how ethanol exposure in adolescence might contribute to later abuse or addiction in adulthood. The present experiment examined effects of intermittent ethanol exposure during adolescence on sign-tracking behavior in adulthood, indexed by a Pavlovian conditioned approach (PCA) task wherein an 8s lever presentation served as a cue predicting subsequent delivery of a flavored food pellet. Although no response was required for food delivery, after multiple pairings, 1 of 2 different responses often emerged during the lever presentation: goal tracking (head entries into the food trough) or sign tracking (engagement with the lever when presented). Sign tracking is thought to reflect the attribution of incentive salience to reward-paired cues and has been previously correlated with addiction-like behaviors. Following the last PCA session, blood samples were collected for analysis of post-session corticosterone levels. Sixty-two rats (n = 10-12/group) were pseudo-randomly assigned to 1 of 2 intragastric (i.g.) exposure groups (water or 4 g/kg ethanol) or a non-manipulated (NM) control group. Animals were intubated with ethanol or water every other session from postnatal session (PND) 28-48 or PND 70-90. Rats were then tested in adulthood (PND 71-79 or PND 113-122) on the PCA task. Animals exposed chronically to ethanol during adolescence exhibited significantly higher levels of sign-tracking behavior in adulthood than NM and water-treated animals, and showed higher corticosterone than NM control animals. These effects were not seen after comparable ethanol exposure in adulthood. These results suggest that adolescent alcohol exposure has long-term consequences on the expression of potential addiction-relevant behaviors in adulthood. Copyright © 2014

  17. Epigenetic Effects of Ethanol on the Liver and Gastrointestinal System

    PubMed Central

    Shukla, Shivendra D.; Lim, Robert W.

    2013-01-01

    The widening web of epigenetic regulatory mechanisms also encompasses ethanol-induced changes in the gastrointestinal (GI)–hepatic system. In the past few years, increasing evidence has firmly established that alcohol modifies several epigenetic parameters in the GI tract and liver. The major pathways affected include DNA methylation, different site-specific modifications in histone proteins, and microRNAs. Ethanol metabolism, cell-signaling cascades, and oxidative stress have been implicated in these responses. Furthermore, ethanol-induced fatty liver (i.e., steatohepatitis) and progression of liver cancer (i.e., hepatic carcinoma) may be consequences of the altered epigenetics. Modification of gene and/or protein expression via epigenetic changes also may contribute to the cross-talk among the GI tract and the liver as well as to systemic changes involving other organs. Thus, epigenetic effects of ethanol may have a central role in the various pathophysiological responses induced by ethanol in multiple organs and mediated via the liver–GI axis. PMID:24313164

  18. Child-related cognitions and affective functioning of physically abusive and comparison parents.

    PubMed

    Haskett, Mary E; Smith Scott, Susan; Grant, Raven; Ward, Caryn Sabourin; Robinson, Canby

    2003-06-01

    The goal of this research was to utilize the cognitive behavioral model of abusive parenting to select and examine risk factors to illuminate the unique and combined influences of social cognitive and affective variables in predicting abuse group membership. Participants included physically abusive parents (n=56) and a closely-matched group of comparison parents (n=62). Social cognitive risk variables measured were (a) parent's expectations for children's abilities and maturity, (b) parental attributions of intentionality of child misbehavior, and (c) parents' perceptions of their children's adjustment. Affective risk variables included (a) psychopathology and (b) parenting stress. A series of logistic regression models were constructed to test the individual, combined, and interactive effects of risk variables on abuse group membership. The full set of five risk variables was predictive of abuse status; however, not all variables were predictive when considered individually and interactions did not contribute significantly to prediction. A risk composite score computed for each parent based on the five risk variables significantly predicted abuse status. Wide individual differences in risk across the five variables were apparent within the sample of abusive parents. Findings were generally consistent with a cognitive behavioral model of abuse, with cognitive variables being more salient in predicting abuse status than affective factors. Results point to the importance of considering diversity in characteristics of abusive parents.

  19. Binge ethanol exposure increases the Krüppel-like factor 11-monoamine oxidase (MAO) pathway in rats: Examining the use of MAO inhibitors to prevent ethanol-induced brain injury

    PubMed Central

    Duncan, Jeremy W.; Zhang, Xiao; Wang, Niping; Johnson, Shakevia; Harris, Sharonda; Udemgba, Chinelo; Ou, Xiao-Ming; Youdim, Moussa B.; Stockmeier, Craig A.; Wang, Jun Ming

    2016-01-01

    Binge drinking induces several neurotoxic consequences including oxidative stress and neurodegeneration. Because of these effects, drugs which prevent ethanol-induced damage to the brain may be clinically beneficial. In this study, we investigated the ethanol-mediated KLF11-MAO cell death cascade in the frontal cortex of Sprague–Dawley rats exposed to a modified Majchowicz 4-day binge ethanol model and control rats. Moreover, MAO inhibitors (MAOIs) were investigated for neuroprotective activity against binge ethanol. Binge ethanol-treated rats demonstrated a significant increase in KLF11, both MAO isoforms, protein oxidation and caspase-3, as well as a reduction in BDNF expression in the frontal cortex compared to control rats. MAOIs prevented these binge ethanol-induced changes, suggesting a neuroprotective benefit. Neither binge ethanol nor MAOI treatment significantly affected protein expression levels of the oxidative stress enzymes, SOD2 or catalase. Furthermore, ethanol-induced antinociception was enhanced following exposure to the 4-day ethanol binge. These results demonstrate that the KLF11-MAO pathway is activated by binge ethanol exposure and MAOIs are neuroprotective by preventing the binge ethanol-induced changes associated with this cell death cascade. This study supports KLF11-MAO as a mechanism of ethanol-induced neurotoxicity and cell death that could be targeted with MAOI drug therapy to alleviate alcohol-related brain injury. Further examination of MAOIs to reduce alcohol use disorder-related brain injury could provide pivotal insight to future pharmacotherapeutic opportunities. PMID:26805422

  20. EFFECT OF ETHANOL ON THE NATURAL FERMENTATION OF BENZENE IN GROUNDWATER

    EPA Science Inventory

    Ethanol is commonly used as a fuel oxygenate in California and in the mid continent area around the Great Lakes. The presence of ethanol in a gasoline spill has raised concerns about the effects of the additive on the natural biodegradation of fuel hydrocarbons, including benzen...