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Sample records for acute ethanol intake

  1. 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. PMID:22944615

  2. Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor

    SciTech Connect

    Yogi, Alvaro; Callera, Glaucia E.; Mecawi, André S.; Batalhão, Marcelo E.; Carnio, Evelin C.; Antunes-Rodrigues, José; Queiroz, Regina H.; Touyz, Rhian M.; Tirapelli, Carlos R.

    2012-11-01

    Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin–angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective AT{sub 1} receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P)H oxidase‐mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT{sub 1}-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. -- Highlights: ► Acute ethanol intake stimulates RAS activity and vascular oxidative stress. ► RAS plays a role in acute ethanol-induced oxidative damage via AT{sub 1} receptor activation.

  3. Influence of chronic nicotine intake and acute ethanol challenge on gastric mucus level and blood flow in rabbits.

    PubMed

    Luk, I S; Ho, J; Wong, W M; Yuen, S T; Luk, C T; Cho, C H

    1994-01-01

    The effects of nicotine pretreatment on ethanol-induced gastric mucosal lesions and changes of gastric mucosal mucus levels and blood flow (GBF) were studied in anaesthetized rabbits. Nicotine treatment 25 or 50 micrograms/ml drinking water did not affect the volume of water consumption during the 10-day experimental period. It did not produce gastric mucosal lesions or affect the superficial adherent mucus content. The length of mucus-containing cells and the basal GBF were also unaffected. Intragastric administration of absolute ethanol reduced GBF, this effect was not altered by nicotine. However, the alkaloid potentiated the ulcerogenic actions of ethanol both on lesion formation and mucus depletion evoked by graded oral doses of ethanol (50 or 100%, v/v). Ultrastructurally, the mucous cells were more degenerated in the animals co-treated with nicotine and ethanol. It is concluded that reductions of mucus-containing cells and adherent mucus on the gastric mucosa are likely to be the contributory factors involved in the aggravating action of nicotine on ethanol-induced gastric mucosal lesions in rabbits. PMID:7535712

  4. 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. PMID:19625732

  5. 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

  6. 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. PMID:27286934

  7. Binge ethanol exposure in late gestation induces ethanol aversion in the dam but enhances ethanol intake in the offspring and affects their postnatal learning about ethanol

    PubMed Central

    Chotro, M. Gabriela; Arias, Carlos; Spear, Norman E.

    2009-01-01

    Previous studies show that exposure to 1 or 2 g/kg ethanol during the last days of gestation increases ethanol acceptance in infant rats. We tested whether prenatal exposure to 3 g/kg, a relatively high ethanol dose, generates an aversion to ethanol in both the dam and offspring, and whether this prenatal experience affects the expression of learning derived from ethanol exposure postnatally. The answer was uncertain, since postnatal administration of a 3 g/kg ethanol dose induces an aversion to ethanol after postnatal day 10 but increases ethanol acceptance when administered during the first postnatal week. In the present study pregnant rats received intragastric administrations of water or ethanol (3 g/kg) on gestation days 17-20. On postnatal days 7-8 or 10-11 the offspring were administered water or ethanol (3 g/kg). Intake of ethanol and water, locomotor activity in an open-field and ethanol odor preference were evaluated in the pups, while the mothers were evaluated in terms of ethanol intake. Results indicated an aversion to ethanol in dams that had been administered ethanol during gestation, despite a general increase in ethanol intake observed in their pups relative to controls. The prenatal ethanol exposure also potentiated the increase in ethanol intake observed after intoxication on postnatal days 7-8. Ethanol intoxication on postnatal days 10-11 reduced ethanol consumption; this ethanol aversion was still evident in infant rats exposed prenatally to ethanol despite their general increase in ethanol intake. No effects of prenatal ethanol exposure were observed in terms of motor activity or odor preference. It is concluded that prenatal exposure to ethanol, even in a dose that induces ethanol aversion in the gestating dam, increases ethanol intake in infant rats and that this experience modulates age-related differences in subsequent postnatal learning about ethanol. PMID:19801275

  8. Binge ethanol intoxication heightens subsequent ethanol intake in adolescent, but not adult, rats.

    PubMed

    Fabio, María Carolina; Nizhnikov, Michael E; Spear, Norman E; Pautassi, Ricardo Marcos

    2014-04-01

    A question still to be answered is whether ethanol initiation has a greater effect on ethanol consumption if it occurs during adolescence than in adulthood. This study assessed the effect of ethanol initiation during adolescence or adulthood on voluntary ethanol consumption when animals were still within the same age range. Adolescent or adult rats were given 5, 2, or 0 ethanol exposures. The animals were tested for ethanol consumption through two-bottle choice tests, before undergoing a 1-week deprivation. A two-bottle assessment was conducted after the deprivation. Adolescents, but not adults, given two ethanol administrations during initiation exhibited significantly higher ethanol intake during the pre-deprivation period. These adolescents also exhibited a threefold increase in ethanol intake after 7 days of drug withdrawal, when compared with controls. These findings suggest that very brief experience with binge ethanol intoxication in adolescence, but not in adulthood, impacts later predisposition to drink. PMID:23341340

  9. Brucine suppresses ethanol intake and preference in alcohol-preferring Fawn-Hooded rats

    PubMed Central

    Li, Yu-ling; Liu, Qing; Gong, Qi; Li, Jun-xu; Wei, Shou-peng; Wang, Yan-ting; Liang, Hui; Zhang, Min; Jing, Li; Yong, Zheng; Lawrence, Andrew J; Liang, Jian-hui

    2014-01-01

    Aim: Brucine (BRU) extracted from the seeds of Strychnos nux-vomica L is glycine receptor antagonist. We hypothesize that BRU may modify alcohol consumption by acting at glycine receptors, and evaluated the pharmacodynamic profiles and adverse effects of BRU in rat models of alcohol abuse. Methods: Alcohol-preferring Fawn-Hooded (FH/Wjd) rats were administered BRU (10, 20 or 30 mg/kg, sc). The effects of BRU on alcohol consumption were examined in ethanol 2-bottle-choice drinking paradigm, ethanol/sucrose operant self-administration paradigm and 5-d ethanol deprivation test. In addition, open field test was used to assess the general locomotor activity of FH/Wjd rats, and conditioned place preference (CPP) was conducted to assess conditioned reinforcing effect. Results: In ethanol 2-bottle-choice drinking paradigm, treatment with BRU for 10 consecutive days dose-dependently decreased the ethanol intake associated with a compensatory increase of water intake, but unchanged the daily total fluid intake and body weight. In ethanol/sucrose operant self-administration paradigms, BRU (30 mg/kg) administered before each testing session significantly decreased the number of lever presses for ethanol and the ethanol intake, without affecting the number of sucrose (10%) responses, total sucrose intake, and the number of lever presses for water. Acute treatment with BRU (30 mg/kg) completely suppressed the deprivation-induced elevation of ethanol consumption. Treatment with BRU (10, 20, and 30 mg/kg) did not alter locomotion of FH/Wjd rats, nor did it produce place preference or aversion. Conclusion: BRU selectively decreases ethanol consumption with minimal adverse effects. Therefore, BRU may represent a new pharmacotherapy for alcoholism. PMID:24909512

  10. 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. PMID:19273846

  11. Amphetamine modifies ethanol intake of psychosocially stressed male rats.

    PubMed

    Pohorecky, Larissa A; Sweeny, April

    2012-05-01

    Studies of socially housed rodents have provided significant information regarding the consequences of exposure to stressors. Psychosocial stressors are known to alter the ingestion of ethanol and the activity of the dopaminergic neuronal system. Since both stressors and ethanol are known to affect the function of dopaminergic neurons, we employed amphetamine to assess the role of this neural system on the ingestion of ethanol by psychosocially stressed male rats. Male rats housed two per cage were designated as dominant or subdominant rats based on evaluations of agonistic behavior and body weight changes. The dyad-housed rats and a group of single-housed rats were sequentially assessed for ethanol intake after injections of saline or amphetamine (0.3, 0.9 or 2.7 mg/kg i.p.) both prior to dyad housing and subsequently again during dyad-housing. Prior to dyad housing ethanol intake of future subdominant rats was higher than that of future dominant rats. Dyad-housing significantly increased ethanol intake of dominant rats. Pre-dyad the highest dose of amphetamine potently depressed ethanol ingestion. Sensitivity to amphetamine's depressant effect on ethanol intake was higher at the dyad test in all subjects, most prominently in single-housed rats. In contrast to the single-housed rats, the dyad-housed rats displayed saccharin anhedonia. It can be concluded that dopaminergic system modulates, at least partially, the psychosocial stress-induced changes in ethanol intake. Furthermore, the level of ethanol ingestion at the pre-dyad test was predictive of future hierarchical status. PMID:22285324

  12. Effects of caffeine and Bombesin on ethanol and food intake

    SciTech Connect

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

    1991-01-01

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

  13. High ethanol dose during early adolescence induces locomotor activation and increases subsequent ethanol intake during late adolescence.

    PubMed

    Acevedo, María Belén; Molina, Juan Carlos; Nizhnikov, Michael E; Spear, Norman E; Pautassi, Ricardo Marcos

    2010-07-01

    Adolescent initiation of ethanol consumption is associated with subsequent heightened probability of ethanol use disorders. The present study examined the relationship between motivational sensitivity to ethanol initiation in adolescent rats and later ethanol intake. Experiment 1 determined that ethanol induces locomotor activation shortly after administration but not if tested at a later post-administration interval. In Experiment 2, adolescent rats were assessed for ethanol-induced locomotor activation on postnatal Day 28. These animals were then evaluated for ethanol-mediated conditioned taste aversion and underwent a 16-day-long ethanol intake protocol. Ethanol-mediated aversive effects were unrelated to ethanol locomotor stimulation or subsequent ethanol consumption patterns. Ethanol intake during late adolescence was greatest in animals initiated to ethanol earliest at postnatal Day 28. Females that were more sensitive to ethanol's locomotor-activating effects showed a transient increase in ethanol self-administration. Blood ethanol concentrations during initiation were not related to ethanol-induced locomotor activation. Adolescent rats appeared sensitive to the locomotor-stimulatory effects of ethanol. Even brief ethanol exposure during adolescence may promote later ethanol intake. PMID:20373327

  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. Acute and chronic exposure to ethanol and the electrophysiology of the brush border membrane of rat small intestine.

    PubMed Central

    al-Balool, F; Debnam, E S; Mazzanti, R

    1989-01-01

    In this study we have investigated the effects of (a) chronic ethanol intake on glucose and galactose absorption across the rat jejunum in vivo and on the potential difference across the isolated brush border membrane (Vm) and (b) acute exposure to ethanol (4% or 8%) and acetaldehyde (0.25%) on changes in Vm associated with Na(+)-dependent galactose absorption across the jejunum and ileum. Chronic ethanol intake was associated with hyperpolarization of Vm and an enhanced galactose but not glucose transport. Acute ethanol and acetaldehyde were without effect on Vm whether or not galactose was present. We conclude that while a greater electrochemical gradient across the brush border membrane is a likely explanation for the stimulation of galactose absorption induced by ethanol feeding, factors other than changes in Vm are responsible for the inhibitory effects of acute ethanol. PMID:2612984

  16. 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

  17. 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

  18. Effect on intake valve deposits of ethanol and additives common to the available ethanol supply

    SciTech Connect

    Shibolm, C.M.; Schoonveld, G.A.

    1990-01-01

    With the widespread introduction of the third generation additives to modern gasolines, the author's company chose to further define the effects of gasoline/ethanol blends (gasohol) on intake system deposits (ISD). The third generation additives referred to here are those that provide protection against ISD. This paper presents detailed results of the investigation in this area. During evaluation of various ISD additives, it was found that additive levels capable of controlling ISD with normal gasolines were unable to do so with fuels containing neat ethanol. Most fuel grade ethanol available in the marketplace is pretreated with additives intended to control accumulation of port fuel injector (PFI) deposits. These currently accepted PFI additives proved to be even more of a problem to intake valves than neat ethanol in gasoline. Some, however, contributed more to valve deposits than others. Data for this investigation was generated via the Modified IVD Test in BMW vehicles at an independent laboratory. Results identify that proper gasoline and ethanol additive combinations and treatment levels can provide satisfactory ISD protection in gasoline engines.

  19. Effects of gamma-hydroxybutyric acid and flunitrazepam on ethanol intake in male rats.

    PubMed

    Leonard, Stuart T; Gerak, Lisa R; Gurkovskaya, Olga; Moerschbaecher, Joseph M; Winsauer, Peter J

    2006-12-01

    Both gamma-hydroxybutyric acid (GHB) and flunitrazepam are often used illicitly in combination with ethanol. Nevertheless, the effects that these and other drugs of abuse have on the reinforcing effects of ethanol remain inconclusive. To test the effects of GHB and flunitrazepam on contingent ethanol intake, twelve male Long-Evans rats were trained to orally consume ethanol using a saccharin-fading procedure. After training, all animals preferentially consumed ethanol instead of water at each of five ethanol concentrations (0-32%) when tested with a two-bottle preference test in the homecage. Animals then received a noncontingent dose of ethanol (0.32, 0.56, 1, and 1.33 g/kg), flunitrazepam (0.032, 0.1, and 0.32 mg/kg), or GHB (100, 180, 320, and 560 mg/kg) prior to each subject's daily access to ethanol (18% v/v). Noncontingent doses of ethanol decreased ethanol intake, however, the subjects consumed enough ethanol to maintain a consistent total ethanol dose in g/kg. Flunitrazepam did not affect ethanol intake at any dose tested, whereas GHB only affected intake at the highest dose (560 mg/kg), a dose that also produced sedation. These data suggest that there are perceptible or qualitative differences between GHB, flunitrazepam, and ethanol in terms of their capacity for modulating oral ethanol intake in outbred rats. PMID:17208286

  20. Modulation of ethanol-intake by morphine: Evidence for a central site of action

    SciTech Connect

    Wild, K.D.; Reid, L.D. )

    1990-01-01

    Previous studies have shown that subcutaneous administration of low doses of morphine increase, while subcutaneous naloxone decreases, ethanol-intake in rats. However, the site of action of morphine modulation of ethanol-intake remains unclear. In an attempt to elucidate this issue, seven graded doses of morphine were given intracerebroventricularly to rats 15 min prior to an opportunity to consume water and sweetened alcoholic beverage for 2 hr. Two lower doses of intracerebroventricular morphine reliably increased ethanol-intake, while higher doses decreased intake of water. Preference ratios were reliably increased by morphine doses of 1 {mu}g and higher. The present data provide support for a central site of morphine modulation of ethanol-intake.

  1. ACUTE ETHANOL SUPPRESSES GLUTAMATERGIC NEUROTRANSMISSION THROUGH ENDOCANNABINOIDS IN HIPPOCAMPAL NEURONS

    PubMed Central

    Basavarajappa, Balapal S.; Ninan, Ipe; Arancio, Ottavio

    2008-01-01

    Ethanol exposure during fetal development is a leading cause of long-term cognitive impairments. Studies suggest that ethanol exposure have deleterious effects on the hippocampus, a brain region that is important for learning and memory. Ethanol exerts its effects, in part, via alterations in glutamatergic neurotransmission, which is critical for the maturation of neuronal circuits during development. The current literature strongly supports the growing evidence that ethanol inhibits glutamate release in the neonatal CA1 hippocampal region. However, the exact molecular mechanism responsible for this effect is not well understood. In this study, we show that ethanol enhances endocannabinoid (EC) levels in cultured hippocampal neurons, possibly through calcium pathways. Acute ethanol depresses miniature postsynaptic current (mEPSC) frequencies without affecting their amplitude. This suggests that ethanol inhibits glutamate release. The CB1 receptors (CB1Rs) present on presynaptic neurons are not altered by acute ethanol. The CB1R antagonist SR 141716A reverses ethanol-induced depression of mEPSC frequency. Drugs that are known to enhance the in vivo function of ECs occlude ethanol effects on mEPSC frequency. Chelation of postsynaptic calcium by EGTA antagonizes ethanol-induced depression of mEPSC frequency. The activation of CB1R with the selective agonist WIN55,212-2 also suppresses the mEPSC frequency. This WIN55,212-2 effect is similar to the ethanol effects and is reversed by SR141716A. In addition, tetani-induced excitatory postsynaptic currents (EPSCs) are depressed by acute ethanol. SR141716A significantly reverses ethanol effects on evoked EPSC amplitude in a dual recording preparation. These observations, taken together, suggest the participation of ECs as retrograde messengers in the ethanol-induced depression of synaptic activities. PMID:18796007

  2. Alcoholic fatty liver in rats: Role of fat and ethanol intake

    SciTech Connect

    Sankaran, H.; Deveney, C.W. ); Larkin, E.C.; Rao, G.A. )

    1991-03-11

    The claim that high intake of both ethanol and fat is essential to induce fatty liver and high blood alcohol levels (BAL) was tested. Two groups of rats were fed liquid diets containing 26% and 36% of calories as ethanol respectively. After 4 weeks, all rats were bled for BAL and some were sacrificed to obtain liver morphology. Remaining rats in Group 1 (26% ethanol) were switched to 36% ethanol diet and Group 2 (36% ethanol) to 26% ethanol diet. All rats were sacrificed after 4 weeks to obtain blood for BAL and liver morphology. The results indicate that high ethanol intake and high fat ingestion is not the criterion for induction of fatty liver. Inadequate ingestion of macronutrients plays a major role in alcoholic fatty liver and BAL.

  3. 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

  4. Prenatal ethanol increases ethanol intake throughout adolescence, alters ethanol-mediated aversive learning, and affects μ but not δ or κ opioid receptor mRNA expression.

    PubMed

    Fabio, María Carolina; Macchione, Ana Fabiola; Nizhnikov, Michael E; Pautassi, Ricardo Marcos

    2015-06-01

    Animal models of prenatal ethanol exposure (PEE) have indicated a facilitatory effect of PEE on adolescent ethanol intake, but few studies have assessed the effects of moderate PEE throughout adolescence. The mechanisms underlying this facilitatory effect remain largely unknown. In the present study, we analysed ethanol intake in male and female Wistar rats with or without PEE (2.0 g/kg, gestational days 17-20) from postnatal days 37 to 62. The results revealed greater ethanol consumption in PEE rats than in controls, which persisted throughout adolescence. By the end of testing, ethanol ingestion in PEE rats was nearly 6.0 g/kg. PEE was associated with insensitivity to ethanol-induced aversion. PEE and control rats were further analysed for levels of μ, δ and κ opioid receptor mRNA in the infralimbic cortex, nucleus accumbens shell, and ventral tegmental area. Similar levels of mRNA were observed across most areas and opioid receptors, but μ receptor mRNA in the ventral tegmental area was significantly increased by PEE. Unlike previous studies that assessed the effects of PEE on ethanol intake close to birth, or in only a few sessions during adolescence, the present study observed a facilitatory effect of PEE that lasted throughout adolescence. PEE was associated with insensitivity to the aversive effect of ethanol, and increased levels of μ opioid receptor transcripts. PEE is a prominent vulnerability factor that probably favors the engagement of adolescents in risky trajectories of ethanol use. PMID:25865037

  5. Regulation of brain anandamide by acute administration of ethanol

    PubMed Central

    Ferrer, Belen; Bermúdez-Silva, Francisco Javier; Bilbao, Ainhoa; Alvarez-Jaimes, Lily; Sanchez-Vera, Irene; Giuffrida, Andrea; Serrano, Antonia; Baixeras, Elena; Khaturia, Satishe; Navarro, Miguel; Parsons, Loren H.; Piomelli, Daniele; Rodríguez de Fonseca, Fernando

    2007-01-01

    The endogenous cannabinoid acylethanolamide AEA (arachidonoylethanolamide; also known as anandamide) participates in the neuroadaptations associated with chronic ethanol exposure. However, no studies have described the acute actions of ethanol on AEA production and degradation. In the present study, we investigated the time course of the effects of the intraperitoneal administration of ethanol (4 g/kg of body mass) on the endogenous levels of AEA in central and peripheral tissues. Acute ethanol administration decreased AEA in the cerebellum, the hippocampus and the nucleus accumbens of the ventral striatum, as well as in plasma and adipose tissue. Parallel decreases of a second acylethanolamide, PEA (palmitoylethanolamide), were observed in the brain. Effects were observed 45–90 min after ethanol administration. In vivo studies revealed that AEA decreases were associated with a remarkable inhibition of the release of both anandamide and glutamate in the nucleus accumbens. There were no changes in the expression and enzymatic activity of the main enzyme that degrades AEA, the fatty acid amidohydrolase. Acute ethanol administration did not change either the activity of N-acyltransferase, the enzyme that catalyses the synthesis of the AEA precursor, or the expression of NAPE-PLD (N-acylphosphatidylethanolamine-hydrolysing phospholipase D), the enzyme that releases AEA from membrane phospholipid precursors. These results suggest that receptor-mediated release of acylethanolamide is inhibited by the acute administration of ethanol, and that this effect is not derived from increased fatty acid ethanolamide degradation. PMID:17302558

  6. Acamprosate-responsive brain sites for suppression of ethanol intake and preference

    PubMed Central

    Brager, Allison; Prosser, Rebecca A.

    2011-01-01

    Acamprosate suppresses alcohol intake and craving in recovering alcoholics; however, the central sites of its action are unclear. To approach this question, brain regions responsive to acamprosate were mapped using acamprosate microimplants targeted to brain reward and circadian areas implicated in alcohol dependence. mPer2 mutant mice with nonfunctional mPer2, a circadian clock gene that gates endogenous timekeeping, were included, owing to their high levels of ethanol intake and preference. Male wild-type (WT) and mPer2 mutant mice received free-choice (15%) ethanol/water for 3 wk. The ethanol was withdrawn for 3 wk and then reintroduced to facilitate relapse. Four days before ethanol reintroduction, mice received bilateral blank or acamprosate-containing microimplants releasing ∼50 ng/day into reward [ventral tegmental (VTA), peduculopontine tegmentum (PPT), and nucleus accumbens (NA)] and circadian [intergeniculate leaflet (IGL) and suprachiasmatic nucleus (SCN)] areas. The hippocampus was also targeted. Circadian locomotor activity was measured throughout. Ethanol intake and preference were greater in mPer2 mutants than in wild-type (WT) mice (27 g·kg−1·day−1 vs. 13 g·kg−1·day−1 and 70% vs. 50%, respectively; both, P < 0.05). In WTs, acamprosate in all areas, except hippocampus, suppressed ethanol intake and preference (by 40–60%) during ethanol reintroduction. In mPer2 mutants, acamprosate in the VTA, PPT, and SCN suppressed ethanol intake and preference by 20–30%. These data are evidence that acamprosate's suppression of ethanol intake and preference are manifest through actions within major reward and circadian sites. PMID:21697518

  7. Regulation of ethanol intake under chronic mild stress: roles of dopamine receptors and transporters

    PubMed Central

    Delis, Foteini; Rombola, Christina; Bellezza, Robert; Rosko, Lauren; Grandy, David K.; Volkow, Nora D.; Thanos, Panayotis K.

    2015-01-01

    Studies have shown that exposure to chronic mild stress decreases ethanol intake and preference in dopamine D2 receptor wild-type mice (Drd2+/+), while it increases intake in heterozygous (Drd2+/−) and knockout (Drd2−/−) mice. Dopaminergic neurotransmission in the basal forebrain plays a major role in the reinforcing actions of ethanol as well as in brain responses to stress. In order to identify neurochemical changes associated with the regulation of ethanol intake, we used in vitro receptor autoradiography to measure the levels and distribution of dopamine D1 and D2 receptors and dopamine transporters (DAT). Receptor levels were measured in the basal forebrain of Drd2+/+, Drd2+/−, and Drd2−/− mice belonging to one of four groups: control (C), ethanol intake (E), chronic mild stress exposure (S), and ethanol intake under chronic mild stress (ES). D2 receptor levels were higher in the lateral and medial striatum of Drd2+/+ ES mice, compared with Drd2+/+ E mice. Ethanol intake in Drd2+/+ mice was negatively correlated with striatal D2 receptor levels. D2 receptor levels in Drd2+/− mice were the same among the four treatment groups. DAT levels were lower in Drd2+/− C and Drd2−/− C mice, compared with Drd2+/+ C mice. Among Drd2+/− mice, S and ES groups had higher DAT levels compared with C and E groups in most regions examined. In Drd2−/− mice, ethanol intake was positively correlated with DAT levels in all regions studied. D1 receptor levels were lower in Drd2+/− and Drd2−/− mice, compared with Drd2+/+, in all regions examined and remained unaffected by all treatments. The results suggest that in normal mice, ethanol intake is associated with D2 receptor-mediated neurotransmission, which exerts a protective effect against ethanol overconsumption under stress. In mice with low Drd2 expression, where DRD2 levels are not further modulated, ethanol intake is associated with DAT function which is upregulated under stress leading to ethanol

  8. Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala.

    PubMed

    Robinson, Stacey L; Alexander, Nancy J; Bluett, Rebecca J; Patel, Sachin; McCool, Brian A

    2016-09-01

    The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA. Chronic ethanol exposure significantly alters eCB system expression within regions critical to the expression of emotionality and anxiety-related behavior, including the BLA. Here, we investigated specific interactions between the BLA eCB system and its functional regulation of synaptic activity during acute and chronic ethanol exposure. In tissue from ethanol naïve-rats, a prolonged acute ethanol exposure caused a dose dependent inhibition of glutamatergic synaptic activity via a presynaptic mechanism that was occluded by CB1 antagonist/inverse agonists SR141716a and AM251. Importantly, this acute ethanol inhibition was attenuated following 10 day chronic intermittent ethanol vapor exposure (CIE). CIE exposure also significantly down-regulated CB1-mediated presynaptic inhibition at glutamatergic afferent terminals but spared CB1-inhibition of GABAergic synapses arising from local inhibitory-interneurons. CIE also significantly elevated BLA N-arachidonoylethanolamine (AEA or anandamide) levels and decreased CB1 receptor protein levels. Collectively, these data suggest a dynamic regulation of the BLA eCB system by acute and chronic ethanol. PMID:26707595

  9. Inflexible ethanol intake: A putative link with the Lrrk2 pathway.

    PubMed

    da Silva E Silva, Daniel Almeida; Frozino Ribeiro, Andrea; Damasceno, Samara; Rocha, Cristiane S; Berenguer de Matos, Alexandre H; Boerngen-Lacerda, Roseli; Correia, Diego; Brunialti Godard, Ana Lúcia

    2016-10-15

    Alcoholism is a complex multifactorial disorder with a strong genetic influence. Although several studies have shown the impact of high ethanol intake on the striatal gene expression, few have addressed the relationship between the patterns of gene expression underlying the compulsive behaviour associated with the two major concerns in addiction: the excessive drug consumption and relapsing. In this study, we used a chronic three-bottle free-choice murine model to address striatal transcript regulation among animals with different ethanol intakes and preferences: Light Drinkers (preference for water throughout the experiment), Heavy Drinkers (preference for ethanol with a non-compulsive intake) and Inflexible Drinkers (preference for ethanol and simultaneous loss of control over the drug intake). Our aim was to correlate the intake patterns observed in this model with gene expression changes in the striatum, a brain region critical for the development of alcohol addiction. We found that the transcripts of the Lrrk2 gene, which encodes a multifunctional protein with kinase and GTPase activities, is upregulated only in Inflexible Drinkers suggesting, for the first time, that the Lrrk2 pathway plays a major role in the compulsive ethanol intake behaviour of addicted subjects. PMID:27411784

  10. Effect of natural and synthetic polyamines on ethanol intake in UChB drinker rats.

    PubMed

    Bilbeny, Norberto; Contreras, Selfa; Font, María; Paeile, Carlos; García, Hernán

    2005-07-01

    Because of the important glutamatergic mediation of the behavioral effects of ethanol, glutamatergic agents have attracted attention for the treatment of ethanol abuse and dependence in preclinical and clinical studies. In the present study, we investigated the effect of pharmacological doses of the natural polyamines putrescine, spermine, and spermidine and the synthetic polyamine N,N'-bis-(3-aminopropyl)cyclohexane-1,4-diamine (DCD) on alcohol consumption in a free-choice paradigm carried out in genetically high-ethanol-consumer UChB rats. Short 3-day treatment with either polyamine, administered p.o., significantly reduced ethanol intake without modifying water and food intakes. Neither polyamine was able to increase markedly blood acetaldehyde in rats submitted to a standard challenge dose of ethanol, to rule out a disulfiram-like effect. Besides, blood ethanol disappearance after a test dose of ethanol was not affected by the synthetic polyamine DCD. Long-term treatment with DCD dose-dependently reduced ethanol intake in UChB rats without producing any observable effect on overt behavior, food consumption, and total fluid intake. The present results indicate that pharmacological doses of polyamines can reduce ethanol consumption in genetically drinking rats without producing significant side effects, suggesting that modulation of brain N-methyl-d-aspartate receptors by polyamines could represent a suitable strategy to reduce appetite for ethanol. However, caution must be exercised in interpreting the results because polyamines can also affect neuronal excitability by acting at other receptor targets, such as AMPA and kainate receptors, as well as at some voltage-dependent ion channels. PMID:16377458

  11. The anti-fatty liver effects of garlic oil on acute ethanol-exposed mice.

    PubMed

    Zeng, Tao; Guo, Fang-Fang; Zhang, Cui-Li; Zhao, Sheng; Dou, Dan-Dan; Gao, Xu-Cong; Xie, Ke-Qin

    2008-11-25

    The protective effects of single dose of garlic oil (GO) on acute ethanol-induced fatty liver were investigated. Mice were treated with ethanol (4.8 g/kg bw) to induce acute fatty liver. The liver index, the serum and hepatic triglyceride (TG) levels and the histological changes were examined to evaluate the protective effects. Hepatic malondialdehyde (MDA), glutathione (GSH) levels and superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) activities were determined for the antioxidant capacity assay. Acute ethanol exposure resulted in the enlargement of the liver index and the increase of the serum and hepatic TG levels (P<0.01), which were dramatically attenuated by GO pretreatment in a dose-dependent manner (P<0.01). GO treatment (simultaneously with ethanol exposure) exhibited similar effects to those of pretreatment, while no obviously protective effects were displayed when it was used at 2h after ethanol intake. Histological changes were paralleled to these indices. Beside this, GO dramatically prolonged the drunken time and shortened the waking time, and these effects were superior to those of silymarin and tea polyphenol. In addition, GO dose-dependently suppressed the elevation of MDA levels, restored the GSH levels and enhanced the SOD, GR and GST activities. Compared with the ethanol group, the MDA levels decreased by 14.2% (P<0.05), 29.9% and 32.8% (P<0.01) in GO groups 50, 100 and 200 mg/kg, respectively. The GST activity increased by 9.97%, 19.94% (P<0.05) and 42.12% (P<0.01) of the ethanol group in GO groups 50, 100 and 200 mg/kg, respectively, while the GR activity increased by 28.57% (P<0.05), 37.97% (P<0.01), 50.45% (P<0.01) of the ethanol group in GO groups 50, 100 and 200 mg/kg, respectively. These data indicated that single dose of GO possessed ability to prevent acute ethanol-induced fatty liver, but may lose its capacity when used after ethanol exposure. The protective effects

  12. Ethanol intake of chickens treated with fenfluramine, fluoxetine, and dietary tryptophan.

    PubMed

    Lu, M R; Wagner, G C; Fisher, H

    1992-10-01

    Male, white leghorn chickens fed a standard diet with or without tryptophan supplementation were treated with single injections of 8 mg/kg fenfluramine in one series of experiments, or 8 mg/kg fluoxetine in another series. The birds had been food- and water-deprived prior to injection. They were offered, following the drug or saline injection, water, a 5% ethanol solution, or an isocaloric sucrose solution (8.75%) for 1 hr. Both fluoxetine and fenfluramine significantly reduced consumption of the ethanol solution, an effect exacerbated by tryptophan supplementation. Water or sucrose solution intake was also significantly reduced, but significantly less so than ethanol after fenfluramine injection. Since the birds drank significantly more of the sucrose solution after saline injection than of water, the consumption decrease caused by fenfluramine resulted, nevertheless, in a higher intake than that of either water or ethanol. Body temperature was decreased by ethanol intake and/or fluoxetine injection. Fenfluramine injection had an opposite, body temperature-increasing effect. It appears that both fenfluramine and fluoxetine decrease ethanol intake in a manner more specific than for water or sucrose, and that this effect is amplified by dietary tryptophan supplementation. PMID:1443420

  13. Actions of acute and chronic ethanol on presynaptic terminals.

    PubMed

    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

    2006-02-01

    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 intoxication

  14. Chronic ethanol intake leads to structural and molecular alterations in the rat endometrium.

    PubMed

    Martinez, Marcelo; Milton, Flora A; Pinheiro, Patricia Fernanda F; Almeida-Francia, Camila C D; Cagnon-Quitete, Valeria H A; Tirapelli, Luiz F; Padovani, Carlos Roberto; Chuffa, Luiz Gustavo A; Martinez, Francisco Eduardo

    2016-05-01

    We described the effects of low- and high-dose ethanol intake on the structure and apoptosis signaling of the uterine endometrium of UChA and UChB rats (animals with voluntary ethanol consumption). Thirty adult female rats, 90 days old, were divided into three groups (n = 10/group): UChA rats fed with 10% (v/v) ethanol ad libitum (free choice for water or ethanol) drinking < 1.9 g/kg/day; UChB rats fed with 10% (v/v) ethanol ad libitum (free choice for water or ethanol) drinking from 2 to 5 g/kg/day; control rats without ethanol (only water). After 120 days of treatment, rats displaying estrus were euthanized. Uterine epithelial cells of the UCh rats showed dilated cisterns of the rough endoplasmic reticulum, presence of lipid droplets, altered nuclear chromatin, and disrupted mitochondria. The UCh rats exhibited intense atrophied epithelial cells with smaller areas and perimeters of cytoplasm and nuclei. The endometrium of UChA rats showed higher levels of caspase-3 while Xiap and Bcl2 varied from moderate to weak. Both UChA and UChB rats exhibited a stronger immunoreaction to Ki-67 and IGFR-1 on epithelial and stromal cells. Chronic ethanol intake leads to structural and molecular alterations in the uterine endometrium of UCh rats, regardless of low- or high-dose consumption, promoting reproductive disorders. PMID:27139238

  15. Photoperiodic modulation of voluntary ethanol intake in C57BL/6 mice.

    PubMed

    Rosenwasser, A M; Fixaris, M C; McCulley, W D

    2015-08-01

    Seasonal and geographic variations in light exposure influence human mood and behavior, including alcohol consumption. Similarly, manipulation of the environmental lighting regimen modulates voluntary ethanol intake in experimental animals. Nevertheless, previous studies in rats and hamsters have been somewhat inconsistent, and little is known concerning such effects in mice. In the present study, we maintained male C57Bl/6 mice in running-wheel cages under either short- or long-photoperiod light-dark cycles (LD 6:18 vs. LD 18:6); subsequently, the same animals were maintained under short or long "skeleton photoperiods", consisting of two daily 15-min light pulses signaling dusk and dawn (SP 6:18 vs. SP 18:6). Running wheels were locked mechanically for half the animals under each photoperiod. Analysis of running wheel patterns showed that mice displayed stable circadian adaptation to both standard LD cycles and skeleton photoperiods. Mice consumed more ethanol and less water, and thus showed higher ethanol preference, under LD 6:18 and SP 6:18 relative to the corresponding long-photoperiod regimens. While running-wheel access increased water intake, ethanol intake was unaffected by this manipulation. These effects are consistent with previous studies showing that short photoperiods or constant darkness increases ethanol intake in rodents. Further, the similarity of the effects of complete and skeleton photoperiods suggests that these effects are mediated by photoperiod-induced alterations in the circadian entrainment pattern, rather than by light exposure per se. PMID:25992479

  16. Refeeding after acute food restriction: differential reduction in preference for ethanol and ethanol-paired flavors in selectively bred rats.

    PubMed

    Dess, Nancy K; Chapman, Clinton D; Cousins, Laura A; Monroe, Derek C; Nguyen, Phuong

    2013-01-17

    Rats' voluntary ethanol intake varies with dispositional factors and energy status. The joint influences of these were of interest here. We previously reported that rats selectively bred for high voluntary saccharin intake (HiS) consume more ethanol and express more robust conditioning of preference for flavors paired with voluntarily consumed ethanol than do low-saccharin consuming counterparts (LoS). Three new experiments examined the effect of refeeding after an episode of food restriction on ethanol intake and on preference for ethanol-paired flavors in HiS and LoS rats. A 48-h episode of food restriction with wheel running reduced intake of and preference for 4% ethanol (Exp. 1a) and preference for an ethanol-paired flavor (Exp. 1b) during refeeding. Food restriction alone was sufficient to reduce the flavor preference (Exp. 2). Adding fat to the refeeding diet or extending the food restriction period exacerbated the effect (Exp. 3), yielding a frank aversion to ethanol-paired flavors in LoS rats. These studies indicate that rebound from negative energy balance shifts responses to ethanol-associated cues from preference toward aversion. Analyses of bodyweight changes and caloric intake during refeeding support this conclusion and further suggest that lower metabolic efficiency may be a marker for enhanced preference mutability. PMID:23231850

  17. Voluntary Ethanol Intake Predicts κ-Opioid Receptor Supersensitivity and Regionally Distinct Dopaminergic Adaptations in Macaques

    PubMed Central

    Siciliano, Cody A.; Calipari, Erin S.; Cuzon Carlson, Verginia C.; Helms, Christa M.; Lovinger, David M.; Grant, Kathleen A.

    2015-01-01

    The dopaminergic projections from the ventral midbrain to the striatum have long been implicated in mediating motivated behaviors and addiction. Previously it was demonstrated that κ-opioid receptor (KOR) signaling in the striatum plays a critical role in the increased reinforcing efficacy of ethanol following ethanol vapor exposure in rodent models. Although rodents have been used extensively to determine the neurochemical consequences of chronic ethanol exposure, establishing high levels of voluntary drinking in these models has proven difficult. Conversely, nonhuman primates exhibit similar intake and pattern to humans in regard to drinking. Here we examine the effects of chronic voluntary ethanol self-administration on dopamine neurotransmission and the ability of KORs to regulate dopamine release in the dorsolateral caudate (DLC) and nucleus accumbens (NAc) core. Using voltammetry in brain slices from cynomolgus macaques after 6 months of ad libitum ethanol drinking, we found increased KOR sensitivity in both the DLC and NAc. The magnitude of ethanol intake predicted increases in KOR sensitivity in the NAc core, but not the DLC. Additionally, ethanol drinking increased dopamine release and uptake in the NAc, but decreased both of these measures in the DLC. These data suggest that chronic daily drinking may result in regionally distinct disruptions of striatal outputs. In concert with previous reports showing increased KOR regulation of drinking behaviors induced by ethanol exposure, the strong relationship between KOR activity and voluntary ethanol intake observed here gives further support to the hypothesis that KORs may provide a promising pharmacotherapeutic target in the treatment of alcoholism. PMID:25878269

  18. Acute Ethanol Withdrawal Impairs Contextual Learning and Enhances Cued Learning

    PubMed Central

    Tipps, Megan E.; Raybuck, Jonathan D.; Buck, Kari J.; Lattal, K. Matthew

    2014-01-01

    Background Alcohol affects many of the brain regions and neural processes that support learning and memory, and these effects are thought to underlie, at least in part, the development of addiction. Although much work has been done regarding the effects of alcohol intoxication on learning and memory, little is known about the effects of acute withdrawal from a single alcohol exposure. Methods We assess the effects of acute ethanol withdrawal (6 h post-injection with 4 g/kg ethanol) on two forms of fear conditioning (delay and trace fear conditioning) in C57BL/6J and DBA/2J mice. The influence of a number of experimental parameters (pre- and post-training withdrawal exposure; foreground/background processing; training strength; non-associative effects) is also investigated. Results Acute ethanol withdrawal during training had a bidirectional effect on fear conditioned responses, decreasing contextual responses and increasing cued responses. These effects were apparent for both trace and delay conditioning in DBA/2J mice and for trace conditioning in C57BL/6J mice; however, C57BL/6J mice were selectively resistant to the effects of acute withdrawal on delay cued responses. Conclusions Our results show that acute withdrawal from a single, initial ethanol exposure is sufficient to alter long-term learning in mice. In addition, the differences between the strains and conditioning paradigms used suggest that specific learning processes can be differentially affected by acute withdrawal in a manner that is distinct from the reported effects of both alcohol intoxication and withdrawal following chronic alcohol exposure. Thus, our results suggest a unique effect of acute alcohol withdrawal on learning and memory processes. PMID:25684050

  19. Ethanol intake is increased by injection of galanin in the paraventricular nucleus and reduced by a galanin antagonist.

    PubMed

    Rada, Pedro; Avena, Nicole M; Leibowitz, Sarah F; Hoebel, Bartley G

    2004-06-01

    Ethanol intake stimulates expression of galanin in several hypothalamic sites, including the paraventricular nucleus. Because injection of galanin in the paraventricular nucleus induces eating, we hypothesized that galanin might also affect ethanol intake. Rats were given ad libitum access to 4% ethanol for 4 weeks and assigned to one of two groups according to levels of ethanol consumption: high levels (>1.5 g/ kg/day) or low levels (<1.0 g/kg/day). In Experiment 1, galanin (1.0 nmol) or Ringer's solution was injected unilaterally into the paraventricular nucleus, with food and water absent during the first 4 h. Galanin significantly increased ethanol intake only in rats that drank high levels of ethanol. In Experiment 2, injection of galanin (0.5 and 1.0 nmol) in the paraventricular nucleus dose-dependently increased ethanol intake with food and water available. The higher dose was also effective in eliciting ethanol intake when tested with food and water absent. In Experiment 3, a test of receptor specificity was provided by injecting rats with the galanin antagonist M-40 (0.5 nmol) or Ringer's solution. Injection of M-40 in the paraventricular nucleus significantly decreased ethanol consumption. In Experiment 4, an anatomic control, with galanin injected 2 mm dorsal to the paraventricular nucleus in the same animals, caused no change in ethanol intake. In conclusion, injection of galanin in the paraventricular nucleus, at a dose known to induce feeding, acted by means of a galanin receptor to potentiate intake of 4% ethanol, even with food and water available as alternate sources of calories and fluid, respectively. Because ethanol can increase expression of galanin mRNA in the paraventricular nucleus, this could set the stage for a positive feedback loop between galanin and ethanol intake. PMID:15528006

  20. Suppression of ethanol intake in chickens by fenfluramine and dietary tryptophan.

    PubMed

    Fisher, H; Hsu, H C; Wagner, G C

    1991-12-01

    Two groups of 10-week-old White Leghorn cockerels were fed a commercial grower diet with or without an L-tryptophan (0.5%) supplement. After a 24-hr water deprivation and 13 to 14 hr without food, the birds were randomly injected with 0 (saline) 4, 8, or 12 mg of fenfluramine/kg body weight. Thirty minutes after injections, water or a 5% ethanol solution was offered, no choice, to the birds and fluid consumption as well as skin and rectal temperature before and after fluid availability were measured. The ethanol solution in otherwise untreated animals was consumed in similar amounts as water was. Fenfluramine (8 mg/kg) significantly reduced ethanol consumption and tryptophan further significantly reduced ethanol intake. At 12 mg/kg fenfluramine, both water and ethanol intake were sharply reduced. Ethanol decreased body temperature, an effect that was reversed by both tryptophan alone and fenfluramine + tryptophan in a dose-dependent manner. These observations are discussed in reference to the effects of central serotonergic manipulations and ethanol consumption. PMID:1789381

  1. Social Isolation Blunted the Response of Mesocortical Dopaminergic Neurons to Chronic Ethanol Voluntary Intake.

    PubMed

    Lallai, Valeria; Manca, Letizia; Dazzi, Laura

    2016-01-01

    Previous studies have shown that stress can increase the response of mesolimbic dopaminergic neurons to acute administration of drugs of abuse included ethanol. In this study, we investigated the possible involvement of the mesocortical dopaminergic pathway in the development of ethanol abuse under stress conditions. To this aim we trained both socially isolated (SI) and group housed (GH) rats to self administer ethanol which was made available only 2 ha day (from 11:00 to 13:00 h). Rats have been trained for 3 weeks starting at postnatal day 35. After training, rats were surgically implanted with microdialysis probes under deep anesthesia, and 24 hlater extracellular dopamine concentrations were monitored in medial prefrontal cortex (mPFC) for the 2 hpreceding ethanol administration (anticipatory phase), during ethanol exposure (consummatory phase) and for 2 hafter ethanol removal. Results show that, in GH animals, dopamine extracellular concentration in the mPFC increased as early as 80 min before ethanol presentation (+50% over basal values) and remained elevated for 80 min during ethanol exposure. In SI rats, on the contrary, dopamine extracellular concentration did not show any significant change at any time point. Ethanol consumption was significantly higher in SI than in GH rats. Moreover, mesocortical dopaminergic neurons in SI animals also showed a decreased sensitivity to an acute administration of ethanol with respect to GH rats. Our results show that prolonged exposure to stress, as in social isolation, is able to induce significant changes in the response of mesocortical dopaminergic neurons to ethanol exposure and suggest that these changes might play an important role in the compulsivity observed in ethanol addiction. PMID:27378852

  2. Social Isolation Blunted the Response of Mesocortical Dopaminergic Neurons to Chronic Ethanol Voluntary Intake

    PubMed Central

    Lallai, Valeria; Manca, Letizia; Dazzi, Laura

    2016-01-01

    Previous studies have shown that stress can increase the response of mesolimbic dopaminergic neurons to acute administration of drugs of abuse included ethanol. In this study, we investigated the possible involvement of the mesocortical dopaminergic pathway in the development of ethanol abuse under stress conditions. To this aim we trained both socially isolated (SI) and group housed (GH) rats to self administer ethanol which was made available only 2 ha day (from 11:00 to 13:00 h). Rats have been trained for 3 weeks starting at postnatal day 35. After training, rats were surgically implanted with microdialysis probes under deep anesthesia, and 24 hlater extracellular dopamine concentrations were monitored in medial prefrontal cortex (mPFC) for the 2 hpreceding ethanol administration (anticipatory phase), during ethanol exposure (consummatory phase) and for 2 hafter ethanol removal. Results show that, in GH animals, dopamine extracellular concentration in the mPFC increased as early as 80 min before ethanol presentation (+50% over basal values) and remained elevated for 80 min during ethanol exposure. In SI rats, on the contrary, dopamine extracellular concentration did not show any significant change at any time point. Ethanol consumption was significantly higher in SI than in GH rats. Moreover, mesocortical dopaminergic neurons in SI animals also showed a decreased sensitivity to an acute administration of ethanol with respect to GH rats. Our results show that prolonged exposure to stress, as in social isolation, is able to induce significant changes in the response of mesocortical dopaminergic neurons to ethanol exposure and suggest that these changes might play an important role in the compulsivity observed in ethanol addiction. PMID:27378852

  3. Effect of maternal ethanol intake on fetal rabbit gastrointestinal development.

    PubMed

    Guo, W; Gregg, J P; Fonkalsrud, E W

    1994-08-01

    Maternal ingestion of alcohol is believed to be one factor that greatly influences the development of intrauterine growth retardation (IUGR) and postnatal growth failure. The present study was undertaken to determine whether maternally ingested alcohol adversely affects fetal growth and intestinal mucosal function. Five time-mated New Zealand white rabbit does were given ethanol intravenously (ETH group) (30% vol/vol; 1.0 g/kg/d) on gestational days (GD) 15 through 29 (term, 31 days). Two other rabbits received the same dose of ethanol. Maternal, fetal, and amniotic fluid alcohol levels were measured on GD 24. Four control rabbits (SH group) received normal saline (25 mL, intravenously). At term, the animals were delivered by cesarean section and killed. Seventeen of the 42 ETH fetuses survived the study period (43%); all 24 SH fetuses survived. On GD 24, within 60 minutes after maternal ethanol infusion, the fetal blood alcohol concentration (BAC) increased to 153 +/- 1.97 mg/dL (v maternal, 179 +/- 1.75 mg/dL); the amniotic ethanol level increased to 46 +/- 1.32 mg/dL. Birth weight was lower in the ETH group (46.88 +/- 2.21 g) than in the SH group (55.78 +/- 1.80 g) (P < .01). Disaccharidase activity, an indicator of intestinal mucosal function, showed that lactase activity (per milligram of protein) was significantly lower in ETH fetuses (2.60 x 10(-2) +/- 0.22 UE/mg) than in SH fetuses (3.50 x 10(-2) +/- 0.25 UE/mg) (P = .01); maltase activity and protein content were not affected significantly. This report provides the first description of the adverse effects of maternal alcohol ingestion on the small intestinal mucosal function of the fetal rabbit. PMID:7965501

  4. The role of glycerol-3-phosphate dehydrogenase 1 in the progression of fatty liver after acute ethanol administration in mice

    SciTech Connect

    Sato, Tomoki; Morita, Akihito; Mori, Nobuko; Miura, Shinji

    2014-02-21

    Highlights: • Ethanol administration increased GPD1 mRNA expression. • Ethanol administration increased glucose incorporation into TG glycerol moieties. • No increase in hepatic TG levels was observed in ethanol-injected GPD1 null mice. • We propose that GPD1 is required for ethanol-induced TG accumulation in the liver. - Abstract: Acute ethanol consumption leads to the accumulation of triglycerides (TGs) in hepatocytes. The increase in lipogenesis and reduction of fatty acid oxidation are implicated as the mechanisms underlying ethanol-induced hepatic TG accumulation. Although glycerol-3-phosphate (Gro3P), formed by glycerol kinase (GYK) or glycerol-3-phosphate dehydrogenase 1 (GPD1), is also required for TG synthesis, the roles of GYK and GPD1 have been the subject of some debate. In this study, we examine (1) the expression of genes involved in Gro3P production in the liver of C57BL/6J mice in the context of hepatic TG accumulation after acute ethanol intake, and (2) the role of GPD1 in the progression of ethanol-induced fatty liver using GPD1 null mice. As a result, in C57BL/6J mice, ethanol-induced hepatic TG accumulation began within 2 h and was 1.7-fold greater than that observed in the control group after 6 h. The up-regulation of GPD1 began 2 h after administering ethanol, and significantly increased 6 h later with the concomitant escalation in the glycolytic gene expression. The incorporation of {sup 14}C-labelled glucose into TG glycerol moieties increased during the same period. On the other hand, in GPD1 null mice carrying normal GYK activity, no significant increase in hepatic TG level was observed after acute ethanol intake. In conclusion, GPD1 and glycolytic gene expression is up-regulated by ethanol, and GPD1-mediated incorporation of glucose into TG glycerol moieties together with increased lipogenesis, is suggested to play an important role in ethanol-induced hepatic TG accumulation.

  5. The discriminative stimulus properties of ethanol and acute ethanol withdrawal states in rats.

    PubMed

    Gauvin, D V; Harland, R D; Criado, J R; Michaelis, R C; Holloway, F A

    1989-10-01

    Twelve male Sprague-Dawley rats were trained in a standard two-choice Drug 1-Drug 2 discrimination task utilizing 3.0 mg/kg chlordiazepoxide (CDP, an anxiolytic drug) and 20 mg/kg pentylenetetrazol (PTZ, an anxiogenic drug) as discriminative stimuli under a VR 5-15 schedule of food reinforcement. Saline tests conducted at specific time points after acute high doses of ethanol (3.0 and 4.0 g/kg) indicated a delayed rebound effect, evidenced by a shift to PTZ-appropriate responding. Insofar as such a shift in lever selection indexes a delayed anxiety-like state, this acute 'withdrawal' reaction can be said to induce an affective state similar to that seen with chronic ethanol withdrawal states. Ethanol generalization tests: (1) resulted in a dose- and time-dependent biphasic generalization to CDP, (2) failed to block the PTZ stimulus and (3) failed to block the time- and dose-dependent elicitation of an ethanol-rebound effect. These data suggest that ethanol's anxiolytic effects are tenuous. PMID:2791886

  6. An Indian herbal formula (SKV) for controlling voluntary ethanol intake in rats with chronic alcoholism.

    PubMed

    Shanmugasundaram, E R; Shanmugasundaram, K R

    1986-08-01

    Chronic ethanol ingestion in rats showed metabolic and physiological changes similar to alterations reported in human alcoholics. There was a lowering of blood glucose concentration, urea and plasma proteins and elevated concentrations of serum gamma-glutamyl transpeptidase. Administration of SKV, an Ayurvedic formula produced by fermentation of cane sugar with raisins and 12 herbal ingredients brought down voluntary ethanol ingestion in the rats and increased food intake. ECG and EEG studies in alcoholic rats showed cardiac depression, augmentation of frequency and amplitude of the alpha, delta and theta waves and weakness in the beta waves. These changes were reversed during SKV-induced voluntary alcohol restriction. The involvement in the ECG and EEG wave patterns was associated with improvement in blood glucose, plasma protein levels and reduction in gamma glutamyl transpeptidase activities. SKV appeared to have no adverse reaction with ethanol (it contains 1-2% ethanol) and appears to be a promising way to combat alcoholism. PMID:3796018

  7. Effects of dietary protein and ethanol intake on pregnant beagles fed purified diets.

    PubMed

    Switzer, B R; Anderson, J J; Pick, J R

    1986-04-01

    Maternal weight gain of beagles was approximately 50% lower when ethanol was given twice daily at a dose of 1.8 g/kg body weight with either control protein (17% energy from protein) or low protein (8.5%) diet as compared to isocalorically sucrose-treated animals. Similarly, pup birth weights were about 27% lower from beagles given ethanol with either diet when compared to those from sucrose-treated bitches. Two weeks after beginning ethanol treatment, pregnant bitches fed either diet had higher hematocrit values and lower plasma concentrations of albumin and calcium as compared to sucrose-treated animals. Low dietary protein treatment, rather than ethanol, lowered maternal concentrations of red blood cell folate during pregnancy. As compared to sucrose-treated bitches, ethanol prevented folate levels in red blood cells from returning to the normal range by the 9th wk of pregnancy in animals fed low dietary protein. These data show that ethanol consumption and low dietary protein intake, independently of each other, significantly depress maternal weight gain, pup birth weight and some nutritionally related parameters of the mother. PMID:3958813

  8. Low ethanol intake prevents salt-induced hypertension in WKY rats.

    PubMed

    Vasdev, Sudesh; Gill, Vicki; Parai, Sushil; Gadag, Veeresh

    2006-07-01

    Low alcohol intake in humans lowers the risk of coronary heart disease and may lower blood pressure. In hypertension, insulin resistance with altered glucose metabolism leads to increased formation of aldehydes. We have shown that chronic low alcohol intake decreased systolic blood pressure (SBP) and tissue aldehyde conjugates in spontaneously hypertensive rats and demonstrated a strong link between elevated tissue aldehyde conjugates and hypertension in salt-induced hypertensive Wistar-Kyoto (WKY) rats. This study investigated the antihypertensive effect of chronic low alcohol consumption in high salt-treated WKY rats and its effect on tissue aldehyde conjugates, platelet cytosolic free calcium ([Ca2+]i, and renal vascular changes. Animals, aged 7 weeks, were divided into three groups of six animals each. The control group was given normal salt diet (0.7% NaCl) and regular drinking water; the high salt group was given a high salt diet (8% NaCl) and regular drinking water; the high salt + ethanol group was given a high salt diet and 0.25% ethanol in drinking water. After 10 weeks, SBP, platelet [Ca2+]i, and tissue aldehyde conjugates were significantly higher in rats in the high salt group as compared with controls. Animals on high salt diets also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidney. Ethanol supplementation prevented the increase in SBP and platelet [Ca2+]i and aldehyde conjugates in liver and aorta. Kidney aldehyde conjugates and renal vascular changes were attenuated. These results suggest that chronic low ethanol intake prevents salt-induced hypertension and attenuates renal vascular changes in WKY rats by preventing an increase in tissue aldehyde conjugates and cytosolic [Ca2+]i. PMID:16685463

  9. The contribution of electrophysiology to knowledge of the acute and chronic effects of ethanol.

    PubMed

    Little, H J

    1999-12-01

    This review describes the effects of ethanol on the components of neuronal transmission and the relationship of such effects to the behavioural actions of ethanol. The concentrations of ethanol with acute actions on voltage-sensitive ion channels are first described, then the actions of ethanol on ligand-gated ion channels, including those controlled by cholinergic receptors, 5-hydroxytryptamine receptors, the various excitatory amino acid receptors, and gamma-aminobutyric acid receptors. Acute effects of ethanol are then described on brain areas thought to be involved in arousal and attention, the reinforcing effects of ethanol, the production of euphoria, the actions of ethanol on motor control, and the amnesic effects of ethanol; the acute effects of ethanol demonstrated by EEG studies are also discussed. Chronic effects of alcohol on neuronal transmission are described in the context of the various components of the ethanol withdrawal syndrome, withdrawal hyperexcitability, dysphoria and anhedonia, withdrawal anxiety, craving, and relapse drinking. Electrophysiological studies on the genetic influences on the effects of ethanol are discussed, particularly the acute actions of ethanol and electrophysiological differences reported in individuals predisposed to alcoholism. The conclusion notes the concentration of studies on the classical transmitters, with relative neglect of the effects of ethanol on peptides and on neuronal interactions between brain areas and integrated patterns of neuronal activity. PMID:10665833

  10. Exposure to ethanol on prenatal days 19-20 increases ethanol intake and palatability in the infant rat: involvement of kappa and mu opioid receptors.

    PubMed

    Díaz-Cenzano, Elena; Gaztañaga, Mirari; Gabriela Chotro, M

    2014-09-01

    Prenatal exposure to ethanol on gestation Days 19-20, but not 17-18, increases ethanol acceptance in infant rats. This effect seems to be a conditioned response acquired prenatally, mediated by the opioid system, which could be stimulated by ethanol's pharmacological properties (mu-opioid receptors) or by a component of the amniotic fluid from gestation-day 20 (kappa-inducing factor). The latter option was evaluated administering non-ethanol chemosensory stimuli on gestation Days 19-20 and testing postnatal intake and palatability. However, prenatal exposure to anise or vanilla increased neither intake nor palatability of these tastants on postnatal Day 14. In experiment 2, the role of ethanol's pharmacological effect was tested by administering ethanol and selective antagonists of mu and kappa opioid receptors prenatally. Blocking the mu-opioid receptor system completely reversed the effects on intake and palatability, while antagonizing kappa receptors only partially reduced the effects on palatability. This suggests that the pharmacological effect of ethanol on the fetal mu opioid system is the appetitive reinforcer, which induces the prenatally conditioned preference detected in the preweanling period. PMID:24037591

  11. Functional Alterations in the Dorsal Raphe Nucleus Following Acute and Chronic Ethanol Exposure

    PubMed Central

    Lowery-Gionta, Emily G; Marcinkiewcz, Catherine A; Kash, Thomas L

    2015-01-01

    Alcoholism is a pervasive disorder perpetuated in part to relieve negative mood states like anxiety experienced during alcohol withdrawal. Emerging evidence demonstrates a role for the serotonin-rich dorsal raphe (DR) in anxiety following ethanol withdrawal. The current study examined the effects of chronic ethanol vapor exposure on the DR using slice electrophysiology in male DBA2/J mice. We found that chronic ethanol exposure resulted in deficits in social approach indicative of increased anxiety-like behavior at both 24 h and 7 days post-ethanol exposure. At 24 h post-ethanol exposure, we observed increased excitability and decreased spontaneous inhibitory transmission (inhibitory postsynaptic currents, IPSCs) in the DR. At 7 days post-ethanol exposure, we observed increased spontaneous and miniature excitatory transmission (excitatory postsynaptic currents, EPSCs). Because acute ethanol alters GABA transmission in other brain regions, we assessed the effects of ex vivo ethanol (50 mM) on miniature IPSCs (mIPSCs) in the DR 24-h post-ethanol exposure. Bath application of ethanol enhanced the amplitude of mIPSCs in cells from ethanol-naive and chronic intermittent ethanol-exposed (CIE) mice, but significantly enhanced the frequency of mIPSCs only in cells from CIE mice, suggesting that DR neurons are more sensitive to the inhibitory effects of acute ethanol following CIE. On the basis of these findings, we hypothesize that net excitation of DR neurons following chronic ethanol exposure contributes to enhanced anxiety during ethanol withdrawal, and that increased sensitivity of DR neurons to subsequent ethanol exposure may mediate acute ethanol's ability to relieve anxiety during ethanol withdrawal. PMID:25120075

  12. Loss of neurons in the rat basal forebrain cholinergic projection system after prolonged intake of ethanol.

    PubMed

    Arendt, T; Henning, D; Gray, J A; Marchbanks, R

    1988-10-01

    A reduction in the number of acetylcholinesterase (AChE)-positive neurons in the basal nucleus of Meynert complex (NbM, Ch 1 to Ch4) to 83% of control values was observed in rat after ethanol intake (20% v/v) for 12 weeks. Activity of choline acetyltransferase (ChAT) and AChE in the basal forebrain was simultaneously reduced to 74% and 81% and content of acetylcholine (ACh) to 56% of control values respectively. Neuronal loss showed a gradient over the rostro-caudal extension of the cholinergic projection system being most pronounced in the septal-diagonal band area and reaching 27% in the medial septum (Ch1). Number of AChE-positive neurons was insignificantly reduced in the pedunculopontine nucleus (Ch5) and unchanged in the laterodorsal tegmental gray of the periventricular area (Ch6). ACh content and activity of AChE was significantly reduced in target areas of the NbM such as cortex, hippocampus and amygdala, but changes were less pronounced than in the basal nucleus. The results indicate a neurotoxic effect of prolonged intake of ethanol on cholinergic neurons in the NbM leading to a partial cholinergic denervation of cortex, hippocampus and amygdala. Chronic intake of ethanol in rat is suggested to represent an animal model suitable to test the cholinergic hypothesis of geriatric memory dysfunction and to develop strategies for an amelioration of the impairment in memory and cognitive function in dementing disorders associated with a degeneration in the NbM such as postalcoholic dementia and Alzheimer's disease. PMID:2850095

  13. Stress-Induced Enhancement of Ethanol Intake in C57BL/6J Mice with a History of Chronic Ethanol Exposure: Involvement of Kappa Opioid Receptors

    PubMed Central

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

    2016-01-01

    Our laboratory has previously demonstrated that daily forced swim stress (FSS) prior to ethanol drinking sessions facilitates enhanced ethanol consumption in mice with a history of chronic intermittent ethanol (CIE) vapor exposure without altering ethanol intake in air-exposed controls. Because both stress and chronic ethanol exposure have been shown to activate the dynorphin/kappa opioid receptor (KOR) system, the present study was designed to explore a potential role for KORs in modulating stress effects on ethanol consumption in the CIE model of dependence and relapse drinking. After stable baseline ethanol intake was established in adult male C57BL/6J mice, subjects received chronic intermittent exposure (16 h/day × 4 days/week) to ethanol vapor (CIE group) or air (CTL group). Weekly cycles of inhalation exposure were alternated with 5-day limited access drinking tests (1 h access to 15% ethanol). Experiment 1 compared effects of daily FSS and KOR activation on ethanol consumption. CIE and CTL mice were either exposed to FSS (10 min), the KOR agonist U50,488 (5 mg/kg), or a vehicle injection (non-stressed condition) prior to each daily drinking session during test weeks. FSS selectively increased drinking in CIE mice. U50,488 mimicked this effect in CIE mice, but also increased drinking in CTL mice. Experiment 2 assessed effects of KOR blockade on stress-induced drinking in CIE and CTL mice. Stressed and non-stressed mice were administered the short-acting KOR antagonist LY2444296 (0 or 5 mg/kg) 30 min prior to each drinking session during test weeks. FSS selectively increased ethanol consumption in CIE mice, an effect that was abolished by LY2444296 pretreatment. In Experiment 3, CIE and CTL mice were administered one of four doses of U50,488 (0, 1.25, 2.5, 5.0 mg/kg) 1 h prior to each daily drinking test (in lieu of FSS). All doses of U50,488 increased ethanol consumption in both CIE and CTL mice. The U50,488-induced increase in drinking was blocked by LY

  14. Acute ethanol intoxication and the trauma patient: hemodynamic pitfalls.

    PubMed

    Bilello, John; McCray, Victor; Davis, James; Jackson, Lascienya; Danos, Leigh Ann

    2011-09-01

    Many trauma patients are acutely intoxicated with alcohol. Animal studies have demonstrated that acute alcohol intoxication inhibits the normal release of epinephrine, norepinephrine, and vasopressin in response to acute hemorrhage. Ethanol also increases nitric oxide release and inhibits antidiuretic hormone secretion. This article studies the effects of alcohol intoxication (measured by blood alcohol level, BAL) on the presentation and resuscitation of trauma patients with blunt hepatic injuries. A retrospective registry and chart review was conducted of all patients who presented with blunt liver injuries at an ACS-verified, level I trauma center. Data collected included admission BAL, systolic blood pressure, hematocrit, International Normalized Ratio (INR), liver injury grade, Injury Severity Score (ISS), intravenous fluid and blood product requirements, base deficit, and mortality. From September 2002 to May 2008, 723 patients were admitted with blunt hepatic injuries. Admission BAL was obtained in 569 patients, with 149 having levels >0.08%. Intoxicated patients were more likely to be hypotensive on admission (p = 0.01) despite a lower liver injury grade and no significant difference in ISS. There was no significant difference in the percent of intoxicated patients requiring blood transfusion. However, when blood was given, intoxicated patients required significantly more units of packed red blood cells (PRBC) than their nonintoxicated counterparts (p = 0.01). Intoxicated patients also required more intravenous fluid during their resuscitation (p = 0.002). Alcohol intoxication may impair the ability of blunt trauma patients to compensate for acute blood loss, making them more likely to be hypotensive on admission and increasing their PRBC and intravenous fluid requirements. All trauma patients should have BAL drawn upon admission and their resuscitation should be performed with an understanding of the physiologic alterations associated with acute alcohol

  15. Ethanol intake and sup 3 H-serotonin uptake I: A study in Fawn-Hooded rats

    SciTech Connect

    Daoust, M.; Compagnon, P.; Legrand, E.; Boucly, P. )

    1991-01-01

    Ethanol intake and synaptosomal {sup 3}H-serotonin uptake were studied in male Fawn-Hooded and Sprague-Dawley rats. Fawn-Hooded rats consumed more alcohol and more water than Sprague-Dawley rats. Plasma alcohol levels of Sprague-Dawley rats were not detectable but were about 5 mg/dl in Fawn-Hooded rats. Ethanol intake increased the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex, but not in thalamus. In Fawn-Hooded rats, serotonin uptake (Vmax) was higher than in Sprague-Dawley rats cortex. Ethanol intake reduced the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex. In cortex, the carrier affinity for serotonin was increased in alcoholized Fawn-Hooded rats. These results indicate that synaptosomal {sup 3}H-serotonin uptake is affected by ethanol intake. In Fawn-Hooded rats, high ethanol consumption is associated with high serotonin uptake. In rats presenting high serotonin uptake, alcoholization reduces {sup 3}H-serotonin internalization in synaptosomes, indicating a specific sensitivity to alcohol intake of serotonin uptake system.

  16. Effects of repeated light-dark phase shifts on voluntary ethanol and water intake in male and female Fischer and Lewis rats.

    PubMed

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

    2010-05-01

    Several lines of evidence implicate reciprocal interactions between excessive alcohol (ethanol) intake and dysregulation of circadian biological rhythms. Thus, chronic alcohol intake leads to widespread circadian disruption in both humans and experimental animals, while in turn, chronobiological disruption has been hypothesized to promote or sustain excessive alcohol intake. Nevertheless, the effects of circadian disruption on voluntary ethanol intake have not been investigated extensively, and prior studies have reported both increased and decreased ethanol intake in rats maintained under "shift-lag" lighting regimens mimicking those experienced by shift workers and transmeridian travelers. In the present study, male and female inbred Fischer and Lewis rats were housed in running wheel cages with continuous free-choice access to both water and 10% (vol/vol) ethanol solution and exposed to repeated 6-h phase advances of the daily light-dark (LD) cycle, whereas controls were kept under standard LD 12:12 conditions. Shift-lag lighting reduced overall ethanol and water intake, and reduced ethanol preference in Fischer rats. Although contrary to the hypothesis that circadian disruption would increase voluntary ethanol intake, these results are consistent with our previous report of reduced ethanol intake in selectively bred high-alcohol-drinking (HAD1) rats housed under a similar lighting regimen. We conclude that chronic circadian disruption is a form of chronobiological stressor that, like other stressors, can either increase or decrease ethanol intake, depending on a variety of poorly understood variables. PMID:20488643

  17. [Acute hepatitis associated with Colpachi intake. Apropros of 5 cases].

    PubMed

    Bruguera, Miguel; Herrera, Samuel; Lázaro, Edurne; Madurga, Mariano; Navarro, Marta; de Abajo, Francisco J

    2007-02-01

    The use of herbal medicines believed to have therapeutic properties is becoming increasingly widespread. These medicines are usually taken by patients on their own initiative and physicians are often unaware of which patients are taking these substances. Herbal medicines can be taken in the form of teas, powders, and liquid extracts. In the last few years, it has come to light that these natural remedies are not free of risks, especially the risk of interaction with other drugs or hepatotoxicity, ranging from asymptomatic forms to massive hepatic necrosis. We describe a series of 5 patients notified to the Spanish Pharmacovigilance System of medicinal products for human use. All the patients developed acute hepatitis during Colpachi treatment lasting several months, which resolved after discontinuing intake of this substance. Systematic examination of the literature revealed the existence of 6 other reported cases of suspected Colpachi-induced hepatotoxicity. PMID:17335712

  18. Time Course of Elevated Ethanol Intake in Adolescent Relative to Adult Rats Under Continuous, Voluntary-Access Conditions

    PubMed Central

    Vetter, Courtney S.; Doremus-Fitzwater, Tamara L.; Spear, Linda P.

    2007-01-01

    Background Adolescence is a period of elevated alcohol consumption in humans as well as in animal models. Previous studies in our laboratory have shown that adolescent Sprague–Dawley rats consume approximately 2 times more ethanol on a gram per kilogram basis than adult animals in a 2-bottle choice free-access situation. The purpose of the present study was to examine the time course and pattern of elevated ethanol intake during adolescence and the adolescent-to-adult transition, contrast this intake with ontogenetic patterns of food and water intake, and determine whether adolescent access to ethanol elevates voluntary consumption of ethanol in adulthood. Methods Adolescent [postnatal day (P)27–28] and adult (P69–70) male Sprague–Dawley rats were singly housed with continuous access to both water and 1 of 3 experimental solutions in ball-bearing–containing sipper tubes: unsweetened ethanol (10% v/v), sweetened ethanol (10% v/v+0.1% w/v saccharin), and saccharin alone (0.1% w/v). Results Ethanol consumption plateaued at approximately 7.5 g/kg/d during the first 2 weeks of measurement (i.e., P28–39) in early adolescence, before declining sharply at approximately P40 to levels that were only modestly elevated compared with adult-typical consumption patterns that were reached by approximately P70. In contrast, intake of food and total calories showed a more gradual decline into adulthood with no distinguishable plateaus in early adolescence. When adolescent-initiated and adult-initiated animals were tested at the same chronological age in adulthood, animals drank similar amounts regardless of the age at which they were first given voluntary access to ethanol. Conclusions Taken together, these data suggest that the elevated ethanol intake characteristic of early-to-mid adolescence is not simply a function of adolescent-typical hyperphagia or hyperdipsia, but instead may reflect age-related differences in neural substrates contributing to the rewarding or

  19. Binge ethanol withdrawal: Effects on post-withdrawal ethanol intake, glutamate-glutamine cycle and monoamine tissue content in P rat model.

    PubMed

    Das, Sujan C; Althobaiti, Yusuf S; Alshehri, Fahad S; Sari, Youssef

    2016-04-15

    Alcohol withdrawal syndrome (AWS) is a medical emergency situation which appears after abrupt cessation of ethanol intake. Decreased GABA-A function and increased glutamate function are known to exist in the AWS. However, the involvement of glutamate transporters in the context of AWS requires further investigation. In this study, we used a model of ethanol withdrawal involving abrupt cessation of binge ethanol administration (4g/kg/gavage three times a day for three days) using male alcohol-preferring (P) rats. After 48h of withdrawal, P rats were re-exposed to voluntary ethanol intake. The amount of ethanol consumed was measured during post-withdrawal phase. In addition, the expression of GLT-1, GLAST and xCT were determined in both medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). We also measured glutamine synthetase (GS) activity, and the tissue content of glutamate, glutamine, dopamine and serotonin in both mPFC and NAc. We found that binge ethanol withdrawal escalated post-withdrawal ethanol intake, which was associated with downregulation of GLT-1 expression in both mPFC and NAc. The expression of GLAST and xCT were unchanged in the ethanol-withdrawal (EW) group compared to control group. Tissue content of glutamate was significantly lower in both mPFC and NAc, whereas tissue content of glutamine was higher in mPFC but unchanged in NAc in the EW group compared to control group. The GS activity was unchanged in both mPFC and NAc. The tissue content of DA was significantly lower in both mPFC and NAc, whereas tissue content of serotonin was unchanged in both mPFC and NAc. These findings provide important information of the critical role of GLT-1 in context of AWS. PMID:26821293

  20. Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light

    PubMed Central

    Ruby, Christina L; Vadnie, Chelsea A; Hinton, David J; Abulseoud, Osama A; Walker, Denise L; O'Connor, Katheryn M; Noterman, Maria F; Choi, Doo-Sup

    2014-01-01

    Circadian rhythm and sleep disruptions occur frequently in individuals with alcohol use disorders (AUD) and present significant barriers to treatment. Recently, a variant of adenosine transporter, equilibrative nucleoside transporter 1 (ENT1), was associated with the co-occurrence of sleep problems and AUD. We have previously shown that mice lacking ENT1 (ENT1 KO) have reduced adenosine levels in the striatum and drink more alcohol compared with wild types (WT). However, it is unknown whether ENT1 deletion disrupts circadian rhythms, which may contribute to alcohol preference in ENT1 KO mice. Here we used these mice to determine whether endogenous adenosine regulates circadian genetic and behavioral rhythms and influences alcohol intake during chronodisruption. We examined circadian locomotor activity in ENT1 KO vs WT littermates and found that ENT1 KO mice were both active earlier and hyperactive compared with WT mice at night. We used real-time PCR and immunohistochemistry to estimate striatal clock gene levels and found that PER2 expression in the striatum was blunted by ENT1 deletion or A2A receptor (A2AR) antagonism. Next, we exposed ENT1 KO and WT mice to constant light (LL) and found further elevation in ethanol intake in ENT1 KO, but not in WT mice, supporting the notion that circadian dysfunction may contribute to increased alcohol intake in ENT1 KO mice. Finally, we showed that A2AR agonist administration normalized PER1 and PER2 expression and circadian locomotor activity in ENT1 KO mice. Together, our results demonstrate that adenosine signaling regulates cellular and behavioral circadian timing and influences alcohol intake during chronodisruption. PMID:24755889

  1. Adenosinergic regulation of striatal clock gene expression and ethanol intake during constant light.

    PubMed

    Ruby, Christina L; Vadnie, Chelsea A; Hinton, David J; Abulseoud, Osama A; Walker, Denise L; O'Connor, Katheryn M; Noterman, Maria F; Choi, Doo-Sup

    2014-09-01

    Circadian rhythm and sleep disruptions occur frequently in individuals with alcohol use disorders (AUD) and present significant barriers to treatment. Recently, a variant of adenosine transporter, equilibrative nucleoside transporter 1 (ENT1), was associated with the co-occurrence of sleep problems and AUD. We have previously shown that mice lacking ENT1 (ENT1 KO) have reduced adenosine levels in the striatum and drink more alcohol compared with wild types (WT). However, it is unknown whether ENT1 deletion disrupts circadian rhythms, which may contribute to alcohol preference in ENT1 KO mice. Here we used these mice to determine whether endogenous adenosine regulates circadian genetic and behavioral rhythms and influences alcohol intake during chronodisruption. We examined circadian locomotor activity in ENT1 KO vs WT littermates and found that ENT1 KO mice were both active earlier and hyperactive compared with WT mice at night. We used real-time PCR and immunohistochemistry to estimate striatal clock gene levels and found that PER2 expression in the striatum was blunted by ENT1 deletion or A2A receptor (A2AR) antagonism. Next, we exposed ENT1 KO and WT mice to constant light (LL) and found further elevation in ethanol intake in ENT1 KO, but not in WT mice, supporting the notion that circadian dysfunction may contribute to increased alcohol intake in ENT1 KO mice. Finally, we showed that A2AR agonist administration normalized PER1 and PER2 expression and circadian locomotor activity in ENT1 KO mice. Together, our results demonstrate that adenosine signaling regulates cellular and behavioral circadian timing and influences alcohol intake during chronodisruption. PMID:24755889

  2. Effects of concurrent access to multiple ethanol concentrations and repeated deprivations on alcohol intake of high-alcohol-drinking (HAD) rats

    PubMed Central

    Rodd, Zachary A.; Bell, Richard L.; Kuc, Kelly A.; Murphy, James M.; Lumeng, Lawrence; McBride, William J.

    2010-01-01

    High-alcohol-drinking rats, given access to 10% ethanol, expressed an alcohol deprivation effect (ADE) only after multiple deprivations. In alcohol-preferring (P) rats, concurrent access to multiple ethanol concentrations combined with repeated cycles of EtOH access and deprivation produced excessive ethanol drinking. The current study was undertaken to examine the effects of repeated alcohol deprivations with concurrent access to multiple concentrations of ethanol on ethanol intake of HAD replicate lines of rats. HAD-1 and HAD-2 rats received access to 10, 20 and 30% (v/v) ethanol for 6 weeks. Rats from each replicate line were assigned to: (1) a non-deprived group; (2) a group initially deprived of ethanol for 2 weeks; or (3) a group initially deprived for 8 weeks. Following the restoration of the ethanol solutions, cycle of 2 weeks of ethanol exposure and 2 weeks of alcohol deprivation was repeated three times for a total of four deprivations. Following the initial ethanol deprivation period, deprived groups significantly increased ethanol intakes during the initial 24-hour re-exposure period. Multiple deprivations increased ethanol intakes, shifted preference to higher ethanol concentrations and prolonged the duration of the elevated ethanol intakes for up to 5 days. In addition, repeated deprivations increased ethanol intake in the first 2-hour re-exposure period as high as 5–7 g/kg (which are equivalent to amounts consumed in 24 hours by HAD rats), and produced blood ethanol levels in excess of 150 mg%. The results indicate that HAD rats exhibit ‘loss-of-control’ of alcohol drinking with repeated deprivations when multiple ethanol concentrations are available. PMID:19076927

  3. Moderate ingestion of alcohol is associated with acute ethanol-induced suppression of circulating CTX in a PTH-independent fashion.

    PubMed

    Sripanyakorn, Supannee; Jugdaohsingh, Ravin; Mander, Adrian; Davidson, Sarah L; Thompson, Richard Ph; Powell, Jonathan J

    2009-08-01

    The "J shape" curve linking the risk of poor bone health to alcohol intake is now well recognized from epidemiological studies. Ethanol and nonethanol components of alcoholic beverages could influence bone remodeling. However, in the absence of a solid underlying mechanism, the positive association between moderate alcoholic intake and BMD remains questionable because of confounding associated social factors. The objective of this work was to characterize the short-term effects of moderate alcohol consumption on circulating bone markers, especially those involved in bone resorption. Two sequential blood-sampling studies were undertaken in fasted healthy volunteers (age, 20-47 yr) over a 6-h period using beer of different alcohol levels (<0.05-4.6%), solutions of ethanol or orthosilicic acid (two major components of beer), and water +/- calcium chloride (positive and negative controls, respectively). Study 1 (24 subjects) assessed the effects of the different solutions, whereas study 2 (26 subjects) focused on ethanol/beer dose. Using all data in a "mixed effect model," we identified the contributions of the individual components of beer, namely ethanol, energy, low-dose calcium, and high-dose orthosilicic acid, on acute bone resorption. Markers of bone formation were unchanged throughout the study for all solutions investigated. In contrast, the bone resorption marker, serum carboxy terminal telopeptide of type I collagen (CTX), was significantly reduced after ingestion of a 0.6 liters of ethanol solution (>2% ethanol; p ethanol; p < 0.02), or a solution of calcium (180 mg calcium; p < 0.001), but only after calcium ingestion was the reduction in CTX preceded by a significant fall in serum PTH (p < 0.001). Orthosilicic acid had no acute effect. Similar reductions in CTX, from baseline, were measured in urine after ingestion of the test solutions; however, the biological variability in urine CTX was greater

  4. ONTOGENY OF ETHANOL INDUCED MOTOR IMPAIRMENT FOLLOWING ACUTE ETHANOL: ASSESSMENT VIA THE NEGATIVE GEOTAXIS REFLEX IN ADOLESCENT AND ADULT RATS

    PubMed Central

    Ramirez, Ruby Liane; Spear, Linda Patia

    2010-01-01

    Adolescent rats have been observed to be less sensitive than adults to a number of ethanol effects that may serve as feedback cues to reduce further ethanol intake. Among these findings are a few reports of attenuated sensitivities of adolescents to ethanol-induced motor impairment. The purpose of the present study was to further explore potential age-related differences in ethanol-induced motor impairment in both male and female adolescent (postnatal day [P]28–32), and adult (P68-72) Sprague-Dawley rats using an inclined plane assessment of the negative geotaxis reflex. Adult males displayed significant motor impairment at 1.5 g/kg, whereas adolescent males required higher doses, showing significant motor impairment only at doses of 2.25 g/kg ethanol or greater. Intoxicated practice did not significantly influence level of motor impairment at either age. When female rats of both ages were separately analyzed in terms of their response to ethanol, a dose of 1.5 g/kg ethanol was found to significantly impair adults, whereas adolescent females showed significant motor impairment when challenged with 2.25 g/kg but not 1.5 g/kg ethanol. Yet when the 1.5 g/kg data of females at the two ages were directly compared, no significant age difference was seen at this dose. These data document an attenuated sensitivity of adolescent relative to adult rats to the motor impairing effects of ethanol using a stationary inclined plane test, an effect particularly robust in male animals, and demonstrates the utility of this test for assessment of motor coordination in adolescent and adult rats. PMID:20138187

  5. Ethanol intake-induced apoptosis in glial cells and axonal disorders in the cerebellar white matter of UChA rats (voluntary ethanol consumers).

    PubMed

    Martinez, Marcelo; Sauce, Rafael; Oliveira, Suelen Alves; de Almeida Chuffa, Luiz Gustavo; Stefanini, Maíra Aparecida; Lizarte Neto, Fermino Sanches; Takase, Luiz Fernando; Tirapelli, Luiz Fernando; Martinez, Francisco Eduardo

    2015-08-01

    Ethanol intake may cause alterations in cellular metabolism altering motricity, learning and cognition. The cerebellum is one of the most susceptible organs to ethanol-related disorders during development, and is associated with oxidative stress-induced apoptosis being crucial for pathogenic consequences. The UChA variety is a special strain of Wistar rat genetically selected and represents a rare model for the studies related to genetic, biochemical, physiological, nutritional, and pharmacological effects of ethanol. We evaluated the structure and apoptosis in the cerebellar white matter of UChA rats. There were two groups of 09 rats: a control group that did not consume ethanol, and an experimental group of UChA rats that consumed ethanol at 10% (v/v) (<2 g ethanol/kg body weight/day). At 120 days old, rats were anaesthetized followed by decapitation, and their cerebella were collected and fixed. Cerebellar sections were subjected to immunohistochemistry for Caspase-3 and XIAP and transmission electron microscopy (TEM). The UChA group showed more glial cells immunoreactive for caspase-3 and less for XIAP than control group. Alcohol consumption affected myelin integrity. Severe ultrastructural damages in UChA group were observed such as disruption of the myelin sheath, disorganization and deformation of its components, and an increase in the interaxonal spaces. In conclusion, our data demonstrated that ethanol induced apoptosis in the glial cells and promoted an intense change in the myelin sheath of UChA rats, which may cause functional disorders. PMID:26072102

  6. HINDBRAIN AND CRANIAL NERVE DYSMORPHOGENESIS RESULT FROM ACUTE MATERNAL ETHANOL ADMINISTRATION

    EPA Science Inventory

    Acute exposure of mouse embryos to ethanol during stages of hindbrain segmentation results in excessive cell death in specific cell populations. This study details the ethanol-induced cell loss and defines the subsequent effects of this early insult on rhombomere and cranial ner...

  7. Acutely Decreased Thermoregulatory Energy Expenditure or Decreased Activity Energy Expenditure Both Acutely Reduce Food Intake in Mice

    PubMed Central

    Kaiyala, Karl J.; Morton, Gregory J.; Thaler, Joshua P.; Meek, Thomas H.; Tylee, Tracy; Ogimoto, Kayoko; Wisse, Brent E.

    2012-01-01

    Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1) increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2) exercise cessation in mice accustomed to wheel running. Increasing ambient temperature (from 21°C to 28°C) rapidly decreased energy expenditure, demonstrating that thermoregulatory energy expenditure contributes to both light cycle (40±1%) and dark cycle energy expenditure (15±3%) at normal ambient temperature (21°C). Reducing thermoregulatory energy expenditure acutely decreased food intake primarily during the light cycle (65±7%), thus conflicting with the delayed compensation model, but did not alter spontaneous activity. Acute exercise cessation decreased energy expenditure only during the dark cycle (14±2% at 21°C; 21±4% at 28°C), while food intake was reduced during the dark cycle (0.9±0.1 g) in mice housed at 28°C, but during the light cycle (0.3±0.1 g) in mice housed at 21°C. Cumulatively, there was a strong correlation between the change in daily energy expenditure and the change in daily food intake (R2 = 0.51, p<0.01). We conclude that acutely decreased energy expenditure decreases food intake suggesting that energy intake is regulated by metabolic signals that respond rapidly and accurately to reduced energy expenditure. PMID:22936977

  8. Synaptic action of ethanol on cerebellar auditory granule cells reveals acute tolerance

    SciTech Connect

    Huang, C.M.; Liu, G.; Huang, R.H. )

    1991-03-11

    The cerebellum is very sensitive to acute intoxication by ethanol. The authors have recorded electrophysiological responses of granule cells to auditory stimulation from the posterior cerebellar vermis of cats before and after a relatively low dose of ethanol. Auditory responses of granule cells were severely inhibited by ethanol at a transient, peak ethanol concentration of 15-18 mM in the cerebrospinal fluid (CSF). Thereafter, the clearance of ethanol from CSF followed an exponential time course, with 50% of the CSF ethanol being cleared with every passing hour. Auditory responses of granule cells returned to control levels within 60-90 minutes, despite the presence of a DSF ethanol concentration at 8-10mM, indicating acute tolerance. Moreover, a second, identical dose of ethanol, delivered two hours after the first dose produced an attenuated inhibition in the auditory response of cerebellar granule cells. The inhibition took a longer time to be evident but a shorter time to recover than that followed by the first dose of ethanol.

  9. PKCε plays a causal role in acute ethanol-induced steatosis

    PubMed Central

    Kaiser, J. Phillip; Beier, Juliane I.; Zhang, Jun; Hoetker, J. David; von Montfort, Claudia; Guo, Luping; Zheng, Yuting; Monia, Brett P.; Bhatnagar, Aruni; Arteel, Gavin E.

    2009-01-01

    Steatosis is a critical stage in the pathology of alcoholic liver disease (ALD), and preventing steatosis could protect against later stages of ALD. PKCε has been shown to contribute to hepatic steatosis in experimental non-alcoholic fatty liver disease (NAFLD); however, the role of PKCε in ethanol-induced steatosis has not been determined. The purpose of this study was to therefore test the hypothesis that PKCε contributes to ethanol-induced steatosis. Accordingly, the effect of acute ethanol on indices of hepatic steatosis and insulin signaling were determined in PKCε knockout mice and in wild-type mice that received an antisense oligonucleotide (ASO) to knockdown PKCε expression. Acute ethanol (6 g/kg i.g.) caused a robust increase in hepatic non-esterified free fatty acids (NEFA), which peaked 1 h after ethanol exposure. This increase in NEFA was followed by elevated diacylglycerols (DAG), as well as by the concomitant activation of PKCε. Acute ethanol also changed the expression of insulin-responsive genes (i.e. increased G6Pase, downregulated GK), in a pattern indicative of impaired insulin signaling. Acute ethanol exposure subsequently caused a robust increase in hepatic triglycerides. The accumulation of triglycerides caused by ethanol was blunted in ASO-treated or in PKCε−/− mice. Taken together, these data suggest that the increase in NEFA caused by hepatic ethanol metabolism leads to an increase in DAG production via the triacylglycerol pathway. DAG then subsequently activates PKCε, which then exacerbates hepatic lipid accumulation by inducing insulin resistance. These data also suggest that PKCε plays a causal role in at least the early phases of ethanol-induced liver injury. PMID:19022218

  10. Chronic and acute ethanol treatment modifies fluidity and composition in plasma membranes of a human hepatic cell line (WRL-68).

    PubMed

    Gutiérrez-Ruiz, M C; Gómez, J L; Souza, V; Bucio, L

    1995-04-01

    The aim of this study was to compare the effects of chronic (0.1 mol/L ethanol exposure during 30 days) and acute (0.5 mol/L ethanol exposure during 24 h) ethanol treatment on the physical properties and the lipid composition of plasma membranes of the WRL-68 cells (fetal human hepatic cell line). Using fluorescence polarization we found that ethanol treatment reduced membrane anisotropy due to disorganization of acyl chains in plasma membranes and consequently increased fluidity, as measured with the diphenylhexatriene probe. Addition of ethanol in vitro reduced anisotropy in control plasma membranes, whereas chronically ethanol-treated plasma membranes were relatively tolerant to the in vitro addition of ethanol. Acutely ethanol-treated plasma membranes exhibited a smaller anisotropy parameter value than control plasma membranes. We found a decrease in total phospholipid content in acute ethanol WRL-68 plasma membranes. Cholesterol content was increased in both ethanol treatments, and we also found a significant decrease in phosphatidylinositol and phosphatidylcholine and an increase in phosphatidylethanolamine content in ethanol-treated plasma membranes. Our data showed that ethanol treatment decreased the anisotropy parameter consistently with increased fluidity, while increasing the cholesterol/phospholipid ratio of plasma membranes of WRL-68 cells, but only chronically ethanol-treated plasma membranes exhibited tolerance to the in vitro addition of ethanol. It is important to note that some changes that were interpreted as a result of chronic ethanol treatment were also present in short-period ethanol treatments. PMID:7583873

  11. 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

  12. Applications of schedule-induced polydipsia in rodents for the study of an excessive ethanol intake phenotype

    PubMed Central

    Ford, Matthew M.

    2014-01-01

    Schedule-induced polydipsia (SIP) is generated by subjecting a highly motivated animal to a sub-optimal rate of food reinforcement while also providing access to a fluid. SIP is one of several adjunctive (or displacement) behaviors that are expressed in an exaggerated form that is deemed ‘excessive’. This feature makes SIP an attractive model for studying an excessive ethanol drinking phenotype in rodents. Multiple experimental variables are crucial for the full manifestation of adjunctive drinking, including the degree of food deprivation, the inter-pellet interval selected, and the size of the food reward offered. Although these variables were extensively studied and optimized for water polydipsia in rats, a similarly customized approach to ethanol SIP and application of the procedure in mice have largely been curtailed in favor of the default variable values historically used for water SIP in rats. Further, ethanol SIP also requires careful consideration of variables such as taste and ethanol concentration. Investigation of the stress axis and neurochemical systems such as dopamine and serotonin in mediating adjunctive drinking stemmed from two leading hypotheses regarding the underlying mechanisms of SIP generation: 1) SIP as a coping strategy to mitigate stress associated with the aversive environmental condition, and 2) SIP as a displacement of reward in a highly motivated animal. Ethanol SIP is a powerful model of excessive intake because it can generate an ethanol-dependent state and sustain frequent and intoxicating levels of blood ethanol with voluntary oral consumption. The required food deprivation and the loss of the excessive drinking phenotype following removal of the generator schedule are the two main limitations of the model. Future utility of ethanol SIP will be enhanced by more fully dissecting the underlying hormonal and neurochemical mechanisms and optimizing experimental variables for ethanol SIP on a per species and strain basis. PMID

  13. Inhibition of food intake induced by acute stress in rats is due to satiation effects.

    PubMed

    Calvez, J; Fromentin, G; Nadkarni, N; Darcel, N; Even, P; Tomé, D; Ballet, N; Chaumontet, C

    2011-10-24

    Acute mild stress induces an inhibition of food intake in rats. In most studies, the cumulative daily food intake is measured but this only provides a quantitative assessment of ingestive behavior. The present study was designed to analyze the reduction in food intake induced by acute stress and to understand which behavioral and central mechanisms are responsible for it. Two different stressors, restraint stress (RS) and forced swimming stress (FSS), were applied acutely to male Wistar rats. We first measured corticosterone and ACTH in plasma samples collected immediately after acute RS and FSS in order to validate our stress models. We measured food intake after RS and FSS and determined meal patterns and behavioral satiety sequences. The expressions of CRF, NPY and POMC in the hypothalamus were also determined immediately after acute RS and FSS. The rise in corticosterone and ACTH levels after both acute RS and FSS validated our models. Furthermore, we showed that acute stress induced a reduction in cumulative food intake which lasted the whole day for RS but only for the first hour after FSS. For both stressors, this stress-induced food intake inhibition was explained by a decrease in meal size and duration, but there was no difference in ingestion speed. The behavioral satiety sequence was preserved after RS and FSS but grooming was markedly increased, which thus competed with, and could reduce, other behaviors, including eating. Lastly, we showed that RS induced an increase in hypothalamic POMC expression. These results suggest that acute stress may affect ingestive behavior by increasing satiation and to some extent by enhancing grooming, and this may be due to stimulation of the hypothalamic POMC neurons. PMID:21787797

  14. Maternal metallothionein and zinc after acute ethanol exposure during gestation in the rat

    SciTech Connect

    Harris, J.E. )

    1992-02-26

    Acute exposure of the rat fetus to ethanol at critical periods can cause growth retardation and brain damage; the mechanism(s) is not known. Ethanol may cause redistribution of maternal zinc which results in fetal zinc deficiency and subsequent interruption of growth and development. The purpose was to determine if acute ethanol administration to the pregnant rat alters Zn and the Zn binding protein metallothionein (MT) in selected tissues. On gestational day (gd) 14, eighteen pregnant Sprague-Dawley rats were divided into groups. By intragastric tube, ethanol treated dams were given ethanol and pairfed controls were given a 0.85% NaCl solution. On gd 15, intragastric feedings were repeated. Throughout, the Lieber-DeCarli control diet was fed (adlibitum to untreated controls and ethanol treated dams and in appropriate quantities to pair fed controls). Blood ethanol concentrations at 90 minutes after the ethanol dose were 154 {plus minus} 46 and 265 {plus minus} 110 mg% on gd 14 and 15, respectively.

  15. Acute extracellular ethanol load does not produce hyponatremia by internal osmoregulation

    SciTech Connect

    Jackson, J.E.; Tzamaloukas, A.H.; Long, D.A.

    1986-03-05

    Hyponatremia is frequently present in subjects intoxicated with ethanol. To study whether an acute increase in extracellular osmolality by addition of ethanol creates any clinically appreciable osmotic shift of intracellular water extracellularly, they infused over 20 sec 11 mmol/kg of ethanol intravenously into 5 anesthetized dogs (2 with intact renal function, 3 anuric) and measured plasma sodium and ethanol concentrations and osmolality at frequent intervals for 100 min after the end of the infusion. For a range of ethanol concentration between 4 and 120 mmol/l, changes in osmolality were equal to ethanol concentration in plasma water (y = -0.49 + 1.06 x mosm/kg per mmol/l, r = 0.981, p < 0.01). Plasma sodium concentration remained unchanged from baseline throughout the experiments, even at 1 min post-infusion, when osmolality was 78 +/- 25 mosm/kg above the baseline. An acute increase in extracellular osmolality created by rapid intravenous infusion of a large dose of ethanol does not create any osmotic shift of intracellular water extracellularly, that can be detected by dilution of extracellular sodium. The mechanism of hyponatremia in ethanol intoxication is not internal osmoregulation, but abnormalities in external balance of body water and/or solute.

  16. [Acute poisoning due to oral intake of an organic solvent].

    PubMed

    Holtz, J; Nicole, A; Regamey, C

    1992-11-21

    We report a case of paint thinner intoxication by oral intake, with loss of consciousness, upper gastrointestinal injuries, renal failure, rhabdomyolysis and cervical plexus injury. The clinical picture was similar to other cases reported in the literature. PMID:1448688

  17. Development of tolerance to the inhibitory effects of ethanol in the rat isolated vas deferens: effect of acute and chronic ethanol administration in vivo.

    PubMed Central

    DeTurck, K. H.; Pohorecky, L. A.

    1986-01-01

    Contractions of the rat vas deferens elicited by the addition of noradrenaline (NA), K+-depolarizing solutions or by electrical stimulation were recorded before and after incubation with ethanol 181 mM. In tissues from untreated rats, the contractions were inhibited 40-50% by such exposure. Injection of ethanol (2 g kg-1) significantly attenuated ethanol's reduction of peak tension generated by the lowest concentration of NA (10(-4) mM). Chronic administration of ethanol, 18-14 g kg-1 daily for two weeks, resulted in significant tolerance to ethanol. Tissues of treated animals demonstrated ethanol-induced decreases of roughly one-half those of the maltose dextrin (isocaloric) and water (fluid control) groups. This tolerance persisted for at least 48 h after ethanol treatment had been terminated. Overall, the data suggest that ethanol acts both pre- and postsynaptically to produce acute inhibition of smooth muscle contractions or tolerance to these actions upon chronic exposure. PMID:3730699

  18. Evaluation of acute skin irritation and phototoxicity by aqueous and ethanol fractions of Angelica keiskei

    PubMed Central

    LEE, SANG-HAN

    2013-01-01

    In this study, to assess whether aqueous and ethanol fractions of Angelica keiskei induce acute skin irritation and phototoxicity, acute skin irritancy and phototoxicity tests were performed. The skin of rabbits or guinea pigs was treated with these fractions (100 mg/dose) and whether the animals sustained significant skin damage was determined. The data demonstrated that the aqueous and ethanol fractions of Angelica keiskei did not induce acute toxicity in the skin of the animals, as assessed by anatomical and pathological observations. The results from the present study suggest that these aqueous and ethanol fractions of Angelica keiskei have promising potential uses as cosmetic ingredients that do not induce significant levels of skin irritation or phototoxicity. PMID:23251240

  19. Effects of acute ethanol administration on nocturnal pineal serotonin N-acetyltransferase activity

    SciTech Connect

    Creighton, J.A.; Rudeen, P.K.

    1988-01-01

    The effect of acute ethanol administration on pineal serotonin N-acetyltransferase (NAT) activity, norepinephrine and indoleamine content was examined in male rats. When ethanol was administered in two equal doses (2 g/kg body weight) over a 4 hour period during the light phase, the nocturnal rise in NAT activity was delayed by seven hours. The nocturnal pineal norepinephrine content was not altered by ethanol except for a delay in the reduction of NE with the onset of the following light phase. Although ethanol treatment led to a significant reduction in nocturnal levels of pineal serotonin content, there was no significant effect upon pineal content of 5-hydroxyindoleacetic acid (5-HIAA). The data indicate that ethanol delays the onset of the rise of nocturnal pineal NAT activity.

  20. Alterations in rat brain polyphosphoinositide metabolism due to acute ethanol administration.

    PubMed

    Chandrasekhar, R; Huang, H M; Sun, G Y

    1988-04-01

    The effects of acute ethanol administration on the polyphosphoinositide metabolism of rat brain cerebral cortex were examined. Intracerebral injections of [gamma-32P]ATP proved to be an effective in vivo method to prelabel brain phospholipids, especially the polyphosphoinositides. High acute doses of ethanol (8 or 6 g/kg b.wt.) administered by gavage significantly inhibited the breakdown of polyphosphoinositides as judged by an elevation in the concentration as well as the labeling of these compounds. Concomitantly, there was a significant reduction in the level of diacylglycerols. Low acute doses of ethanol (2 g/kg b.wt.) did not seem to have any effects on the basal levels or labeling of these compounds. The changes in polyphosphoinositide labeling due to ethanol intoxication were reverted to near control values when animals regained their righting reflex (approximately 4 hr). These studies demonstrate that, under normal conditions, polyphosphoinositides and diacylglycerols are maintained in a dynamic equilibrium and that acute doses of ethanol can suppress the signal transduction process and disturb this equilibrium. PMID:2834532

  1. Acute and Cytotoxicity Studies of Aqueous and Ethanolic Leaf Extracts of Chromolaena odorata.

    PubMed

    Asomugha, R N; Ezejiofor, A N; Okafor, P N; Ijeh, I I

    2015-01-01

    Chromolaena odorata, a commonly used traditional remedy for different ailments, believed to be quite safe in terms of toxicity was evaluated for acute toxicity and cytotoxic potentials. Acute toxicity was done on albino Wistar rats using the Lorke method while brine shrimps were used to test for cytotoxicity. The results showed that the estimated LD50 for the aqueous and ethanolic extracts was 2154 and > 5000 mg kg(-1) body weight, respectively. Cytotoxicity to brine shrimps showed LC50 values of 324 and 392 ppm for aqueous and ethanolic extracts, respectively. These results indicate the relative non toxic nature of Chromolaena odorata extracts. PMID:26353417

  2. CHRONIC METHYLPHENIDATE TREATMENT DURING EARLY LIFE IS ASSOCIATED WITH GREATER ETHANOL INTAKE IN SOCIALLY ISOLATED RATS

    PubMed Central

    Gill, Kathryn E; Chappell, Ann; Beveridge, Thomas J R; Porrino, Linda J; Weiner, Jeffrey L

    2014-01-01

    Background Methylphenidate is a stimulant prescribed to treat Attention Deficit Hyperactivity Disorder. Its primary mechanism of action is in the dopamine system, alterations of which are associated with vulnerability to alcohol abuse. There are concerns that juvenile MPH treatment may influence adult drinking behavior. This study examined the interaction of MPH treatment and environmental rearing conditions, which are known to independently influence ethanol (EtOH) drinking behavior, on anxiety-like behavior and vulnerability to alcohol abuse in a juvenile rodent model. Methods Male Sprague Dawley rats were housed in enriched, standard, or isolated conditions for four weeks, starting at postnatal day 21. Rats were concurrently treated with 8 mg/kg/day MPH or saline, delivered via osmotic minipump. Anxiety-like behavior was determined at the end of the treatment session, and 5 weeks later. After MPH treatment, rats were exposed to a two-bottle choice EtOH drinking procedure that lasted three weeks. Results Early life chronic MPH treatment was associated with greater EtOH intake and greater EtOH preference, but only in socially isolated animals. Isolated animals had greater levels of anxiety-like behavior than standard-housed or enriched animals after 4 weeks of exposure to the housing conditions, a difference that persisted even after all animals had been individually housed for an additional 5 weeks and exposed to EtOH. Conclusions These results suggest that early life MPH treatment may increase vulnerability to EtOH drinking in adulthood in a subset of the population. Additionally, this study highlights the importance of early rearing condition for establishing long-lasting behavioral phenotypes. Environmental histories should be considered when prescribing MPH treatment to young children. PMID:25156616

  3. Acute behavioural comparisons of toluene and ethanol in human subjects.

    PubMed Central

    Echeverria, D; Fine, L; Langolf, G; Schork, T; Sampaio, C

    1991-01-01

    A comparison of toluene and ethanol (EtOH) induced changes in central nervous system (CNS) function and symptoms were evaluated in two studies, and when possible the effects of toluene were expressed in EtOH equivalent units. The toluene concentrations were 0, 75, and 150 ppm, bracketing the American Conference of Governmental Industrial Hygienists threshold limit value (ACGIH TLV) of 100 ppm. The socially relevant EtOH doses were 0.00, 0.33, and 0.66 g EtOH/kg body weight, equivalent to two and four 3.5% 12 ounce beers. Forty two paid college students were used in each study. In the first study, subjects were exposed to toluene and an odour masking agent menthol (0.078 ppm) for seven hours over three days. In the second study EtOH or a placebo was administered at 1530 across three days also in the presence of menthol. Verbal and visual short term memory (Sternberg, digit span, Benton, pattern memory), perception (pattern recognition), psychomotor skill (simple reaction time, continuous performance, symbol-digit, hand-eye coordination, finger tapping, and critical tracking), manual dexterity (one hole), mood (profile on mood scales (POMS), fatigue (fatigue checklist), and verbal ability were evaluated at 0800, 1200, and 1600. Voluntary symptoms and observations of sleep were collected daily. A 3 x 3 latin square design evaluated solvent effects simultaneously controlling for learning and dose sequence. An analysis of variance and test for trend were performed on am-pm differences reflecting an eight hour workday and on pm scores for each solvent, in which subjects were their own control Intersubject variation in absorbance was monitored in breath. A 5 to 10% decrement was considered meaningful if consistent with a linear trend at p less than 0.05. At 150 ppm toluene, losses in performance were 6.0% for digit span, 12.1% for pattern recognition (latency), 5% for pattern memory (number correct), 6.5% for one hole, and 3% for critical tracking. The number of headaches

  4. Acute ethanol induces apoptosis by stimulating TRPC6 via elevation of superoxide in oxygenated podocytes.

    PubMed

    Lu, Xiao-Yu; Liu, Bing-Chen; Wang, Li-Hua; Yang, Li-Li; Bao, Qing; Zhai, Yu-Jia; Alli, Abdel A; Thai, Tiffany L; Eaton, Douglas C; Wang, Wei-Zhi; Ma, He-Ping

    2015-05-01

    Our recent studies indicate that hydrogen peroxide (H2O2) only at high concentrations can cause oxidative stress in renal epithelial cells and induce apoptosis of podocytes. Consistently, the present study shows that H2O2, even at 1 mM, failed to induce intracellular oxidative stress and apoptosis of the podocytes due to efficient activity of catalase, an enzyme which degrades H2O2 to produce water and oxygen (O2). However, H2O2 acted as a source of O2 to allow acute ethanol to induce superoxide production and cause apoptosis of the podocytes. In contrast, acute ethanol alone did not elevate intracellular superoxide, even though it stimulates expression and translocation of p47phox to the plasma membrane. Inhibition of catalase abolished not only O2 production from H2O2 degradation, but also NOX2-dependent superoxide production in the podocytes challenged by both H2O2 and acute ethanol. In parallel, acute ethanol in the presence of H2O2, but neither ethanol nor H2O2 alone, stimulated transient receptor potential canonical 6 (TRPC6) channels and caused TRPC6-dependent elevation of intracellular Ca2+. These data suggest that exogenous H2O2 does not induce oxidative stress due to rapid degradation to produce O2 in the podocytes, but the oxygenated podocytes become sensitive to acute ethanol challenge and undergo apoptosis via a TRPC6-dependent elevation of intracellular Ca2+. Since cultured podocytes are considered in hypoxic conditions, H2O2 may be used as a source of O2 to establish an ischemia-reperfusion model in some type of cultured cells in which H2O2 does not directly induce intracellular oxidative stress. PMID:25601712

  5. Ethanol intake under social circumstances or alone in Sprague-Dawley rats: Impact of age, sex, social activity and social anxiety-like behavior

    PubMed Central

    Varlinskaya, Elena I.; Truxell, Eric M.; Spear, Linda P.

    2014-01-01

    Background In human adolescents, heavy drinking is often predicted by high sociability in males and high social anxiety in females. This study assessed the impact of baseline levels of social activity and social anxiety-like behavior in group-housed adolescent and adult male and female Sprague-Dawley rats on ethanol intake when drinking alone or in a social group. Methods Social activity and anxiety-like behavior initially were assessed in a modified social interaction test, followed by six drinking sessions that occurred every other day in animals given ad libitum food and water. Sessions consisted of 30-min access to 10% ethanol in a “supersac” (3% sucrose + 0.1% saccharin) solution given alone as well as in groups of five same-sex littermates, with order of the alternating session types counterbalanced across animals. Results Adolescent males and adults of both sexes overall consumed more ethanol under social than alone circumstances, whereas adolescent females ingested more ethanol when alone. Highly socially active adolescent males demonstrated elevated levels of ethanol intake relative to their low and medium socially active counterparts when drinking in groups, but not when tested alone. Adolescent females with high levels of social anxiety-like behavior demonstrated the highest ethanol intake under social, but not alone circumstances. Among adults, baseline levels of social anxiety-like behavior did not contribute to individual differences in ethanol intake in either sex. Conclusions The results clearly demonstrate that in adolescent rats, but not their adult counterparts, responsiveness to a social peer predicts ethanol intake in a social setting – circumstances under which drinking typically occurs in human adolescents. High levels of social activity in males and high levels of social anxiety-like behavior in females were associated with elevated social drinking, suggesting that males ingest ethanol for its socially enhancing properties, whereas

  6. Intermittent (every-other-day) drinking induces rapid escalation of ethanol intake and preference in adolescent and adult C57BL/6J mice

    PubMed Central

    Melendez, Roberto I.

    2010-01-01

    Background Using adult C57BL/6J (B6) mice, we previously developed a procedure that causes a progressive increase in ethanol intake and preference (i.e., alcohol escalation effect) following weekly (intermittent) access to ethanol (Melendez et al. Alcohol Clin Exp Res 30, 2006). A limitation of this procedure is that it requires many weeks of testing, which limits its use to study ethanol escalation (i.e., binge-like drinking) during adolescence. Previous studies have shown that intermittent every-other-day (EOD) access to ethanol is sufficient to induce ethanol escalation in rats. The objective of this study was to verify if EOD access is sufficient to induce escalated levels of ethanol intake and preference in adult and adolescent B6 mice. Methods Male B6 mice received free-choice 24 hr access to 15% ethanol and water on an EOD or daily basis for 2 weeks. Food and water was available at all times. Using adult mice, Experiment 1 characterized the induction of ethanol escalation following EOD access at 6 (i.e., drinking in the dark) and 24 hr intervals, whereas Experiment 2 determined if daily drinking reverses escalation induced by EOD drinking. Experiment 3 compared ethanol-drinking capacity following daily versus EOD drinking in adolescent (P30–45) and adult (P70–85) mice. Results Experiment 1 revealed that EOD drinking leads to a significant (nearly two-fold) increase in ethanol intake and preference over mice given daily access. Experiment 2 demonstrated that EOD-elicited escalation is blocked and subsequently reversed following daily drinking. Experiment 3 revealed that ethanol drinking was greater in adolescent mice compared to adults following daily drinking and EOD (escalated) drinking. Although the escalated levels of ethanol intake were greater in adolescent mice, the rate or onset of escalation was comparable between both age groups. Conclusions This study is the first to demonstrate that EOD drinking leads to escalation of ethanol intake and

  7. Acute Ethanol Inhibition of γ Oscillations Is Mediated by Akt and GSK3β

    PubMed Central

    Wang, JianGang; Zhao, JingXi; Liu, ZhiHua; Guo, FangLi; Wang, Yali; Wang, Xiaofang; Zhang, RuiLing; Vreugdenhil, Martin; Lu, Chengbiao

    2016-01-01

    Hippocampal network oscillations at gamma band frequency (γ, 30–80 Hz) are closely associated with higher brain functions such as learning and memory. Acute ethanol exposure at intoxicating concentrations (≥50 mM) impairs cognitive function. This study aimed to determine the effects and the mechanisms of acute ethanol exposure on γ oscillations in an in vitro model. Ethanol (25–100 mM) suppressed kainate-induced γ oscillations in CA3 area of the rat hippocampal slices, in a concentration-dependent, reversible manner. The ethanol-induced suppression was reduced by the D1R antagonist SCH23390 or the PKA inhibitor H89, was prevented by the Akt inhibitor triciribine or the GSk3β inhibitor SB415286, was enhanced by the NMDA receptor antagonist D-AP5, but was not affected by the MAPK inhibitor U0126 or PI3K inhibitor wortmanin. Our results indicate that the intracellular kinases Akt and GSk3β play a critical role in the ethanol-induced suppression of γ oscillations and reveal new cellular pathways involved in the ethanol-induced cognitive impairment. PMID:27582689

  8. Acute Ethanol Inhibition of γ Oscillations Is Mediated by Akt and GSK3β.

    PubMed

    Wang, JianGang; Zhao, JingXi; Liu, ZhiHua; Guo, FangLi; Wang, Yali; Wang, Xiaofang; Zhang, RuiLing; Vreugdenhil, Martin; Lu, Chengbiao

    2016-01-01

    Hippocampal network oscillations at gamma band frequency (γ, 30-80 Hz) are closely associated with higher brain functions such as learning and memory. Acute ethanol exposure at intoxicating concentrations (≥50 mM) impairs cognitive function. This study aimed to determine the effects and the mechanisms of acute ethanol exposure on γ oscillations in an in vitro model. Ethanol (25-100 mM) suppressed kainate-induced γ oscillations in CA3 area of the rat hippocampal slices, in a concentration-dependent, reversible manner. The ethanol-induced suppression was reduced by the D1R antagonist SCH23390 or the PKA inhibitor H89, was prevented by the Akt inhibitor triciribine or the GSk3β inhibitor SB415286, was enhanced by the NMDA receptor antagonist D-AP5, but was not affected by the MAPK inhibitor U0126 or PI3K inhibitor wortmanin. Our results indicate that the intracellular kinases Akt and GSk3β play a critical role in the ethanol-induced suppression of γ oscillations and reveal new cellular pathways involved in the ethanol-induced cognitive impairment. PMID:27582689

  9. Impact of social isolation and enriched environment during adolescence on voluntary ethanol intake and anxiety in C57BL/6J mice.

    PubMed

    Lopez, Marcelo F; Laber, Kathy

    2015-09-01

    This study was designed to determine the impact of an enriched environment in a previously established stress model of isolation during early development that induces high alcohol (ethanol) self-administration. The study was conducted with male and female C57BL/6J mice housed in isolation or in groups that were either provided or withheld enrichment during adolescence. The impact of these housing conditions was assessed during adulthood by measuring weight gain, quantifying voluntary ethanol intake, measuring plasma corticosterone levels, and assessing anxiety-like behavior. Results showed that, regardless of sex, mice that were single-housed during adolescence showed a significant increase in voluntary ethanol intake, which was not observed in isolated mice that were provided with nesting material during adolescence (compared to group-housed non-enriched control group). Basal corticosterone was not affected by housing, enrichment conditions, or sex. Corticosterone levels did not relate to levels of voluntary ethanol intake. However, corticosterone levels were higher after three weeks of ethanol intake. Surprisingly, mice that were group-housed during adolescence showed higher levels of anxiety-like behavior in the light/dark test. Overall, these results indicate that housing conditions during a critical developmental period can significantly modulate voluntary ethanol intake later in life. PMID:25446196

  10. The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice.

    PubMed

    Blagaic, Alenka Boban; Blagaic, Vladimir; Romic, Zeljko; Sikiric, Predrag

    2004-09-24

    The stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W.1419), which was promising in inflammatory bowel disease (PL-10, PLD-116, PL-14736, Pliva) trials, protects against both acute and chronic alcohol-induced lesions in stomach and liver, but also, given peripherally, affects various centrally mediated disturbances. Now, in male NMRI mice BPC 157 (10 pg intraperitoneally, 10 ng and 10 microg, intraperitoneally or intragastrically) (i) strongly opposed acute alcohol (4 g/kg intraperitoneally) intoxication (i.e., quickly produced and sustained anesthesia, hypothermia, increased ethanol blood values, 25% fatality, 90-min assessment period) given before or after ethanol, and (ii) when given after abrupt cessation of ethanol (at 0 or 3 or 7 h withdrawal time), attenuated withdrawal (assessed through 24 hours) after 20%-alcohol drinking (7.6 g/kg) through 13 days, with provocation on the 14th day. PMID:15381050

  11. Inhibitory Effect of Helicteres gardneriana Ethanol Extract on Acute Inflammation

    PubMed Central

    de Melo, Juliana Oliveira; de Arruda, Laura Lícia Milani; Baroni, Silmara; Truiti, Maria da Conceição Torrado; Caparroz-Assef, Silvana Martins; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Aparecida

    2012-01-01

    The anti-inflammatory effect of an ethanol extract of Helicteres gardneriana (Nees) Castiglioni was assayed in experimental models of pleurisy and microcirculation in situ. Treatment of animals with 500 mg/kg body weight reduced the exudate volume (35% reduction) induced by intrapleural injection of carrageenan and the migration of polymorphonuclear cells into the inflamed pleural cavity of rats (40%). Additionally, rolling and adhesion of leukocytes and the number of leukocytes that migrated toward the perivascular space in response to the carrageenan injection were decreased by the extract (500 mg/kg). These data demonstrate the anti-inflammatory effect of the ethanol extract of Helicteres gardneriana and imply that inhibition of leukocyte-endothelial interactions is important in the extract's mechanism of action. PMID:22028731

  12. Assessment of Expression of Genes Coding GABAA Receptors during Chronic and Acute Intoxication of Laboratory Rats with Ethanol.

    PubMed

    Osechkina, N S; Ivanov, M B; Nazarov, G V; Batotsyrenova, E G; Lapina, N V; Babkin, A V; Berdinskikh, I S; Melekhova, A S; Voitsekhovich, K O; Lisitskii, D S; Kashina, T V

    2016-02-01

    Expression of genes encoding the individual subunits of ionotropic GABAA receptor was assessed after acute and chronic intoxication of rats with ethanol. The chronic 1-month-long exposure to ethanol signifi cantly decreased (by 38%) expression of Gabrb1 gene in the hippocampus. Acute exposure to ethanol elevated expression of genes Gabrb1 (by 1.7 times), Gabra1 (by 3.8 times), and Gabra4 (by 6.5 times), although it diminished expression of Gabra2 gene by 1.4 times. In preliminarily alcoholized rats, acute intoxication with ethanol enhanced expression of genes Gabrb1 and Gabra5 by 1.7 and 8.7 times, respectively. There was neither acute nor chronic effect of ethanol on expression of gene Gabra3. PMID:26902358

  13. [Favism. Acute hemolysis after intake of fava beans].

    PubMed

    Holm, B; Jensenius, M

    1998-01-30

    Acute haemolysis due to Glucose-6-Phosphate-Dehydrogenase deficiency is a common disorder in American and African Blacks, in Mediterranean people and among Orientals. The erythrocytes in affected individuals have insufficient reducing power against toxic peroxydes and free radicals generated during metabolism. Normally, affected individuals are without signs of disease, but under the influence of oxydants severe intravascular haemolysis may occur. One of the most important oxydants is the fava bean which, when ingested, may cause acute favism, a condition which has a 10% mortality if not treated properly. We describe a 35 year-old man from Iraq who developed serious haemolytic anemia with a fall in haemoglobin to 6.5 g/100 ml three days after ingestion of fava beans. He was treated with intravenous fluids and blood transfusions. He recovered and was discharged from hospital after nine days. This is the first described case of favism in Norway. PMID:9499726

  14. Acute effects of ethanol in the control of protein synthesis in isolated rat liver cells

    SciTech Connect

    Girbes, T.; Susin, A.; Ayuso, M.S.; Parrilla, R.

    1983-10-01

    The acute effect of ethanol on hepatic protein synthesis is a rather controversial issue. In view of the conflicting reports on this subject, the effect of ethanol on protein labeling from L-(/sup 3/H)valine in isolated liver cells was studied under a variety of experimental conditions. When tracer doses of the isotope were utilized, ethanol consistently decreased the rate of protein labeling, regardless of the metabolic conditions of the cells. This inhibition was not prevented by doses of 4-methylpyrazole large enough to abolish all the characteristic metabolic effects of ethanol, and it was not related to perturbations on the rates of L-valine transport and/or proteolysis. When ethanol was tested in the presence of saturating doses of L-(/sup 3/H)valine no effect on protein labeling was observed. These observations suggest that the ethanol effect in decreasing protein labeling from tracer doses of the radioactive precursor does not reflect variations in the rate of protein synthesis but reflects changes in the specific activity of the precursor. These changes probably are secondary to variations in the dimensions of the amino acid pool utilized for protein synthesis. Even though it showed a lack of effect when tested alone, in the presence of saturating doses of the radioactive precursor ethanol inhibited the stimulatory effects on protein synthesis mediated by glucose and several gluconeogenic substrates. This effect of ethanol was not prevented by inhibitors of alcohol dehydrogenase, indicating that a shift of the NAD system to a more reduced state is not the mediator of its action. It is suggested that ethanol probably acted by changing the steady-state levels of some common effector(s) generated from the metabolism of all these fuels or else by preventing the inactivation of a translational repressor.

  15. Severe lactic acidosis in a diabetic patient after ethanol abuse and floor cleaner intake.

    PubMed

    Hendrikx, Jeroen J M A; Lagas, Jurjen S; Daling, Ratana; Hooijberg, Jan Hendrik; Schellens, Jan H M; Beijnen, Jos H; Brandjes, Desiderius P M; Huitema, Alwin D R

    2014-11-01

    An intoxication with drugs, ethanol or cleaning solvents may cause a complex clinical scenario if multiple agents have been ingested simultaneously. The situation can become even more complex in patients with (multiple) co-morbidities. A 59-year-old man with type 2 diabetes mellitus (without treatment two weeks before the intoxication) intentionally ingested a substantial amount of ethanol along with ~750 mL of laminate floor cleaner containing citric acid. The patient was admitted with severe metabolic acidosis (both ketoacidosis and lactic acidosis, with serum lactate levels of 22 mM). He was treated with sodium bicarbonate, insulin and thiamine after which he recovered within two days. Diabetic ketoacidosis and lactic acidosis aggravated due to ethanol intoxication, thiamine deficiency and citrate. The high lactate levels were explained by excessive lactate formation caused by the combination of untreated diabetes mellitus, thiamine deficiency and ethanol abuse. Metabolic acidosis in diabetes is multi-factorial, and the clinical situation may be further complicated, when ingestion of ethanol and toxic agents are involved. Here, we reported a patient in whom diabetic ketoacidosis was accompanied by severe lactic acidosis as a result of citric acid and mainly ethanol ingestion and a possible thiamine deficiency. In the presence of lactic acidosis in diabetic ketoacidosis, physicians need to consider thiamine deficiency and ingestion of ethanol or other toxins. PMID:24717115

  16. Effect of ethanol intake on human erythrocyte membrane fluidity and lipid composition.

    PubMed

    Hrelia, S; Lercker, G; Biagi, P L; Bordoni, A; Stefanini, F; Zunarelli, P; Rossi, C A

    1986-05-01

    Erythrocyte membrane fluidity was evaluated in chronic alcoholic patients without any liver alteration, assuming different daily ethanol amounts, and in normal subjects and related to ghost fatty acid and total lipid composition obtained by high resolution gas chromatography. Erythrocyte membrane fluidity was significantly increased in a dose dependent manner in chronic alcoholic patients respect to normal subjects. This real fluidizing effect of ethanol "in vivo" was attributed mainly to a significant increase in the polyunsaturated fatty acids amount in patient ghosts in comparison with control subjects. On the other hand the cholesterol/phospholipid ratio was not significantly affected by chronic ethanol assumption. PMID:3729966

  17. Ethanol Potentiates the Acute Fatty Infiltration of Liver Caused by Burn Injury: Prevention by Insulin Treatment

    PubMed Central

    Emanuele, Nicholas V.; Emanuele, Mary Ann; Morgan, Michelle O.; Sulo, Denise; Yong, Sheri; Kovacs, Elizabeth J.; Himes, Ryan D.; Callaci, John J.

    2011-01-01

    Burn injury is a significant and severe representation of critical illness. Nearly, 50% of patients admitted to hospitals for burn injuries have detectable levels of ethanol in their circulations and these patients have poorer clinical outcomes than burned individuals without measurable circulating ethanol. We report here data on a clinically relevant form of hepatic injury, the development of microvesicular steatosis, in a murine model wherein animals were either given ethanol or saline, and were subjected to burn or sham injury. Because better glycemic control with insulin has been shown in clinical studies to impart major clinical benefit, an additional group of burn ethanol animals were treated with insulin. Insulin significantly reduced blood glucose in injured animals to levels no different from those seen in animals that were neither ethanol exposed nor burned. A single intraperitoneal injection of ethanol was insufficient to raise blood alanine aminotransferase (ALT), measured as an index of liver injury. However, burn injury led to significant increases in ALT at 24 and 48 hours, which had returned to preinjury levels by 7 days. This ALT rise was completely prevented with insulin treatment. A single injection of ethanol did not evoke increased microvesicular steatosis but did potentiate the ability of burn to do so at 24 hours after injury. The burn induced increase in microvesicular steatosis was also seen at 48 hours, but had subsided by 7 days. The increased microvesicular steatosis was prevented by insulin therapy. Thus, ethanol potentiates the ability of burn to cause acute liver injury, which is completely preventable by insulin therapy. These findings may have substantial clinical significance and suggest this model may be useful for the study of the mechanisms of hepatic injury as well as the mechanisms, probably multiple, of insulin action in this setting. PMID:19349879

  18. 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

  19. Acute and Chronic Effects of Ethanol on Learning-Related Synaptic Plasticity

    PubMed Central

    Zorumski, Charles F.; Mennerick, Steven; Izumi, Yukitoshi

    2014-01-01

    Alcoholism is associated with acute and long-term cognitive dysfunction including memory impairment, resulting in substantial disability and cost to society. Thus, understanding how ethanol impairs cognition is essential for developing treatment strategies to dampen its adverse impact. Memory processing is thought to involve persistent, use-dependent changes in synaptic transmission, and ethanol alters the activity of multiple signaling molecules involved in synaptic processing, including modulation of the glutamate and gamma-aminobutyric acid (GABA) transmitter systems that mediate most fast excitatory and inhibitory transmission in the brain. Effects on glutamate and GABA receptors contribute to ethanol-induced changes in long-term potentiation (LTP) and long-term depression (LTD), forms of synaptic plasticity thought to underlie memory acquisition. In this paper, we review the effects of ethanol on learning-related forms of synaptic plasticity with emphasis on changes observed in the hippocampus, a brain region that is critical for encoding contextual and episodic memories. We also include studies in other brain regions as they pertain to altered cognitive and mental function. Comparison of effects in the hippocampus to other brain regions is instructive for understanding the complexities of ethanol’s acute and long-term pharmacological consequences. PMID:24447472

  20. Adenylyl cylases 1 and 8 mediate select striatal-dependent behaviors and sensitivity to ethanol stimulation in the adolescent period following acute neonatal ethanol exposure.

    PubMed

    Susick, Laura L; Lowing, Jennifer L; Bosse, Kelly E; Hildebrandt, Clara C; Chrumka, Alexandria C; Conti, Alana C

    2014-08-01

    Neonatal alcohol exposure in rodents causes dramatic neurodegenerative effects throughout the developing nervous system, particularly in the striatum, acutely after exposure. These acute neurodegenerative effects are augmented in mice lacking adenylyl cyclases 1 and 8 (AC1/8) as neonatal mice with a genetic deletion of both AC isoforms (DKO) have increased vulnerability to ethanol-induced striatal neurotoxicity compared to wild type (WT) controls. While neonatal ethanol exposure is known to negatively impact cognitive behaviors, such as executive functioning and working memory in adolescent and adult animals, the threshold of ethanol exposure required to impinge upon developmental behaviors in mice has not been extensively examined. Therefore, the purpose of this study was to determine the behavioral effects of neonatal ethanol exposure using various striatal-dependent developmental benchmarks and to assess the impact of AC1/8 deletion on this developmental progression. WT and DKO mice were treated with 2.5 g/kg ethanol or saline on postnatal day (P)6 and later subjected to the wire suspension, negative geotaxis, postural reflex, grid hang, tail suspension and accelerating rotarod tests at various time points. At P30, mice were evaluated for their hypnotic responses to 4.0 g/kg ethanol by using the loss of righting reflex assay and ethanol-induced stimulation of locomotor activity after 2.0 g/kg ethanol. Ethanol exposure significantly impaired DKO performance in the negative geotaxis test while genetic deletion of AC1/8 alone increased grid hang time and decreased immobility time in the tail suspension test with a concomitant increase in hindlimb clasping behavior. Locomotor stimulation was significantly increased in animals that received ethanol as neonates, peaking significantly in ethanol-treated DKO mice compared to ethanol-treated WT controls, while sedation duration following high-dose ethanol challenge was unaffected. These data indicate that the

  1. Acute and subacute toxicity evaluation of ethanolic extract from fruits of Schinus molle in rats.

    PubMed

    Ferrero, Adriana; Minetti, Alejandra; Bras, Cristina; Zanetti, Noelia

    2007-09-25

    Ethanolic and hexanic extracts from fruits and leaves of Schinus molle showed ability to control several insect pests. Potential vertebrate toxicity associated with insecticidal plants requires investigation before institutional promotion. The aim of the present study was to evaluate the acute and subacute toxicity of ethanolic extracts from fruits of Schinus molle in rats. The plant extract was added to the diet at 2g/kg body weight/day during 1 day to evaluate acute toxicity and at 1g/kg body weight/day during 14 days to evaluate subacute toxicity. At the end of the exposure and after 7 days, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, histopathological examinations were conducted on several organs. In both exposures, an increase in the arousal level was observed in experimental groups. Also, the landing foot splay parameter increased in the experimental group after acute exposure. Only the subacute exposure produced a significant increase in the motor activity in the open field. All these changes disappeared after 7 days. None of the exposures affected the different organs evaluated. Our results suggest that ethanolic extracts from fruits and leaves of Schinus molle should be relatively safe to use as insecticide. PMID:17716846

  2. Effects of acute ethanol administration of female rat liver as a function of aging

    SciTech Connect

    Rikans, L.E.; Snowden, C.D. )

    1989-01-01

    Female Fischer 344 rats, aged 4, 14, and 25 months, received 4.0 g/kg of ethanol by intraperitoneal (i.p.) injection. Blood alcohol concentrations 2.5, 6 and 16 hr after ethanol injection were similar in the three age groups. Hepatic glutathione (GSH) levels were diminished 6 hr after ethanol injection, and there were no age-dependent differences in the depleted levels (3.2 {plus minus} 0.1, 3.5 {plus minus} 0.2, and 3.0 {plus minus} 0.5 {mu}g GSH/g liver). However, GSH contents in livers of young-adult rats approached control levels after 16 hr, whereas they remained depressed in older rats. Serum levels of hepatic enzymes were significantly elevated 6 hr after ethanol administration. The increases were greater in middle-aged and old rats than in young-adult rats. The results suggest that middle-aged and old rats are more susceptible than young rats to the acute toxicity of ethanol.

  3. Lycopene Pretreatment Ameliorates Acute Ethanol Induced NAD+ Depletion in Human Astroglial Cells

    PubMed Central

    Guest, Jade; Heng, Benjamin; Grant, Ross

    2015-01-01

    Excessive alcohol consumption is associated with reduced brain volume and cognition. While the mechanisms by which ethanol induces these deleterious effects in vivo are varied most are associated with increased inflammatory and oxidative processes. In order to further characterise the effect of acute ethanol exposure on oxidative damage and NAD+ levels in the brain, human U251 astroglioma cells were exposed to physiologically relevant doses of ethanol (11 mM, 22 mM, 65 mM, and 100 mM) for ≤ 30 minutes. Ethanol exposure resulted in a dose dependent increase in both ROS and poly(ADP-ribose) polymer production. Significant decreases in total NAD(H) and sirtuin 1 activity were also observed at concentrations ≥ 22 mM. Similar to U251 cells, exposure to ethanol (≥22 mM) decreased levels of NAD(H) in primary human astrocytes. NAD(H) depletion in primary astrocytes was prevented by pretreatment with 1 μM of lycopene for 3.5 hours. Unexpectedly, in U251 cells lycopene treatment at concentrations ≥ 5 μM resulted in significant reductions in [NAD(H)]. This study suggests that exposure of the brain to alcohol at commonly observed blood concentrations may cause transitory oxidative damage which may be at least partly ameliorated by lycopene. PMID:26075038

  4. Differential gene expression and lipid metabolism in fatty liver induced by acute ethanol treatment in mice

    SciTech Connect

    Yin Huquan; Kim, Mingoo; Kim, Ju-Han; Kong, Gu; Kang, Kyung-Sun; Kim, Hyung-Lae; Yoon, Byung-IL; Lee, Mi-Ock; Lee, Byung-Hoon

    2007-09-15

    Ethanol induces cumulative liver damage including steatosis, steatohepatitis and cirrhosis. The aim of this study is to investigate the global intrahepatic gene expression profile in the mouse liver treated with ethanol. A single oral dose of 0.5 or 5 g/kg ethanol was administered to male ICR mice, and liver samples were obtained after 6, 24 and 72 h. Histopathological evaluation showed typical fatty livers in the high-dose group at 24 h. Microarray analysis identified 28 genes as being ethanol responsive (two-way ANOVA; p < 0.05), after adjustment by the Benjamini-Hochberg multiple testing correction; these genes displayed {>=} 2-fold induction or repression. The expression of genes that are known to be involved in fatty acid synthesis was examined. The transcript for lipogenic transcription factor, sterol regulatory element (SRE)-binding factor 1 (Srebf1), was upregulated by acute ethanol exposure. Of the genes known to contain SRE or SRE-like sequences and to be regulated by SRE-binding protein 1 (SREBP1), those encoding malic enzyme (Mod1), ATP-citrate lyase (Acly), fatty acid synthase (Fasn) and stearyl-CoA desaturase (Scd1) were induced by ethanol. Quantitative real-time PCR confirmed the changes in the expression levels of the selected genes. The change in the Srebf1 mRNA level correlates well with that of the SREBP1 protein expression as well as its binding to the promoters of the target genes. The present study identifies differentially expressed genes that can be applied to the biomarkers for alcohol-binge-induced fatty liver. These results support the hypothesis by which ethanol-induced steatosis in mice is mediated by the fatty acid synthetic pathway regulated by SREBP1.

  5. Protective Effects of the Traditional Herbal Formula Oryeongsan Water Extract on Ethanol-Induced Acute Gastric Mucosal Injury in Rats

    PubMed Central

    Jeon, Woo-Young; Lee, Mee-Young; Shin, In-Sik; Lim, Hye-Sun; Shin, Hyeun-Kyoo

    2012-01-01

    This study was performed to evaluate the protective effect and safety of Oryeongsan water extract (OSWE) on ethanol-induced acute gastric mucosal injury and an acute toxicity study in rats. Acute gastric lesions were induced via intragastric oral administration of absolute ethanol at a dose of 5 mL/kg. OSWE (100 and 200 mg/kg) was administered to rats 2 h prior to the oral administration of absolute ethanol. The stomach of animal models was opened and gastric mucosal lesions were examined. Gastric mucosal injuries were evaluated by measuring the levels of malondialdehyde (MDA), glutathione (GSH), and the activity of antioxidant enzymes. In the acute toxicity study, no adverse effects of OSWE were observed at doses up to 2000 mg/kg/day. Administration of OSWE reduced the damage by conditioning the gastric mucosa against ethanol-induced acute gastric injury, which included hemorrhage, hyperemia, and loss of epithelial cells. The level of MDA was reduced in OSWE-treated groups compared with the ethanol-induced group. Moreover, the level of GSH and the activity of antioxidant enzymes were significantly increased in the OSWE-treated groups. Our findings suggest that OSWE has a protective effect on the gastric mucosa against ethanol-induced acute gastric injury via the upregulation of antioxidant enzymes. PMID:23118790

  6. The novel non-imidazole histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice.

    PubMed

    Bahi, Amine; Sadek, Bassem; Nurulain, Syed M; Łażewska, Dorota; Kieć-Kononowicz, Katarzyna

    2015-11-01

    It has become clear that histamine H3 receptors (H3R) have been implicated in modulating ethanol intake and preference in laboratory animals. The novel non-imidazole H3R antagonist DL77 with excellent selectivity profile shows high in-vivo potency as well as in-vitro antagonist affinity with ED50 of 2.1 ± 0.2 mg/kg and pKi=8.08, respectively. In the present study, and applying an unlimited access two-bottle choice procedure, the anti-alcohol effects of the H3R antagonist, DL77 (0, 3, 10 and 30 mg/kg; i.p.), were investigated in adult mice. In this C57BL/6 line, effects of DL77 on voluntary alcohol intake and preference, as well as on total fluid intake were evaluated. Results have shown that DL77, dose-dependently, reduced both ethanol intake and preference. These effects were very selective as both saccharin and quinine, used to control for taste sensitivity, and intakes were not affected following DL77 pre-application. More importantly, systemic administration of DL77 (10 mg/kg) during acquisition inhibited ethanol-induced conditioned-place preference (EtOH-CPP) as measured using an unbiased protocol. The anti-alcohol activity observed for DL77 was abrogated when mice were pretreated with the selective H3R agonist R-(α)-methyl-histamine (RAMH) (10 mg/kg), or with the CNS penetrant H1R antagonist pyrilamine (PYR) (10mg/kg). These results suggest that DL77 has a predominant role in two in vivo effects of ethanol. Therefore, signaling via H3R is essential for ethanol-related consumption and conditioned reward and may represent a novel therapeutic pharmacological target to tackle ethanol abuse and alcoholism. PMID:26169446

  7. CHRONIC ETHANOL INTAKE IMPAIRS INSULIN SIGNALING IN RATS BY DISRUPTING AKT ASSOCIATION WITH THE CELL MEMBRANE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic and excessive alcohol consumption is an important and modifiable risk factor for type 2 diabetes. We previously reported elevations in Class 1 Alcohol Dehydrogenase (ADH) expression in ethanol-fed rats that were coincident with reduced levels of mature, nuclear SREBP-1, suggesting that this ...

  8. Acute Cor Pulmonale and Right Heat Failure Complicating Ethanol Ablative Therapy: Anesthetic and Radiologic Considerations and Management

    SciTech Connect

    Naik, Bhiken; Matsumoto, Alan H.

    2013-10-15

    Ethanol is an effective ablative agent used for the treatment of certain solid organ tumors and vascular malformations (VMs). The egress of ethanol beyond the target tissue can be associated with significant changes to the cardiopulmonary system that can lead to cardiac arrest. This article reviews the contemporary role of ethanol in tumor and VM treatment and discusses the physiological mechanisms of acute pulmonary hypertension and cardiovascular collapse. The importance of periprocedural recognition of the hemodynamic changes that can occur with the use of ethanol and the treatment of this condition are discussed.

  9. 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

  10. Acute exposure to ethanol on gestational day 15 affects social motivation of female offspring.

    PubMed

    Varlinskaya, Elena I; Mooney, Sandra M

    2014-03-15

    Alterations in social behavior are a hallmark of many neurodevelopmental disorders in humans. In rodents, social behavior is affected by prenatal insults. The outcomes are dependent on the timing of the insult as well as the sex and age of the animal tested. The limbic system is particularly important for social behavior, and a peak of neurogenesis within this system occurs on gestational day (G)15. Neurons appear particularly vulnerable to ethanol insult around the time they become post-mitotic. We tested the hypothesis that acute exposure to ethanol on G15 would result in significant social behavior deficits. Accordingly, Long Evans pregnant females were injected with ethanol (2.9 g/kg) or an equivalent volume of saline on G15. Offspring were assessed in a modified social interaction test on postnatal day (P) 28, P42, or P75, i.e., during early adolescence, late adolescence, or young adulthood. Prenatal ethanol exposure decreased social investigation in P28 females and transformed social preference into social avoidance in 75-day-old females. Contact behavior, play fighting, and locomotor activity differed as a function of age, but were not significantly affected by ethanol exposure. Males demonstrated significantly more contact behavior and play fighting at P42 than at P28 or P70, whereas there were no age-related changes in females. Adult females showed more locomotor activity than adult males. Overall, prenatal ethanol exposure on G15 enhanced social anxiety in females, with these effects seen in adulthood only. PMID:24355753

  11. In Vivo Acute on Chronic Ethanol Effects in Liver: A Mouse Model Exhibiting Exacerbated Injury, Altered Metabolic and Epigenetic Responses

    PubMed Central

    Shukla, Shivendra D.; Aroor, Annayya R.; Restrepo, Ricardo; Kharbanda, Kusum K.; Ibdah, Jamal A.

    2015-01-01

    Chronic alcoholics who also binge drink (i.e., acute on chronic) are prone to an exacerbated liver injury but its mechanism is not understood. We therefore investigated the in vivo effects of chronic and binge ethanol ingestion and compared to chronic ethanol followed by three repeat binge ethanol on the liver of male C57/BL6 mice fed ethanol in liquid diet (4%) for four weeks followed by binge ethanol (intragastric administration, 3.5 g/kg body weight, three doses, 12h apart). Chronic followed by binge ethanol exacerbated fat accumulation, necrosis, decrease in hepatic SAM and SAM:SAH ratio, increase in adenosine levels, and elevated CYP2E1 levels. Histone H3 lysine acetylation (H3AcK9), dually modified phosphoacetylated histone H3 (H3AcK9/PS10), and phosphorylated H2AX increased after binge whereas phosphorylation of histone H3 ser 10 (H3S10) and H3 ser 28 (H3S28) increased after chronic ethanol-binge. Histone H3 lysine 4 and 9 dimethylation increased with a marked dimethylation in H3K9 in chronic ethanol binge group. Trimethylated histone H3 levels did not change. Nuclear levels of histone acetyl transferase GCN5 and histone deacetylase HDAC3 were elevated whereas phospho-CREB decreased in a distinctive manner. Taken together, acute on chronic ethanol ingestion caused amplification of liver injury and elicited characteristic profiles of histone modifications, metabolic alterations, and changes in nuclear protein levels. These findings demonstrate that chronic ethanol exposure renders liver more susceptible to repeat acute/binge ethanol induced acceleration of alcoholic liver disease. PMID:26610587

  12. Amoxicillin and amoxicillin/clavulanate reduce ethanol intake and increase GLT-1 expression as well as AKT phosphorylation in mesocorticolimbic regions.

    PubMed

    Goodwani, Sunil; Rao, P S S; Bell, Richard L; Sari, Youssef

    2015-10-01

    Studies have shown that administration of the β-lactam antibiotic ceftriaxone (CEF) attenuates ethanol consumption and cocaine seeking behavior as well as prevents ethanol-induced downregulation of glutamate transporter 1 (GLT-1) expression in central reward brain regions. However, it is not known if these effects are compound-specific. Therefore, the present study examined the effects of two other β-lactam antibiotics, amoxicillin (AMOX) and amoxicillin/clavulanate (Augmentin, AUG), on ethanol drinking, as well as GLT-1 and phosphorylated-AKT (pAKT) levels in the nucleus accumbens (Acb) and medial prefrontal cortex (mPFC) of alcohol-preferring (P) rats. P rats were exposed to free-choice of ethanol (15% and 30%) for five weeks and were given five consecutive daily i.p. injections of saline vehicle, 100 mg/kg AMOX or 100mg/kg AUG. Both compounds significantly decreased ethanol intake and significantly increased GLT-1 expression in the Acb. AUG also increased GLT-1 expression in the mPFC. Results for changes in pAKT levels matched those for GLT-1, indicating that β-lactam antibiotic-induced reductions in ethanol intake are negatively associated with increases in GLT-1 and pAKT levels within two critical brains regions mediating drug reward and reinforcement. These findings add to a growing literature that pharmacological increases in GLT-1 expression are associated with decreases in ethanol intake and suggest that one mechanism mediating this effect may be increased phosphorylation of AKT. Thus, GLT-1 and pAKT may serve as molecular targets for the treatment of alcohol and drug abuse/dependence. PMID:26168897

  13. The influence of acute or chronic nicotine treatment on ethanol-induced gastric mucosal damage in rats.

    PubMed

    Cho, C H; Chen, B W; Hui, W M; Lam, S K

    1990-01-01

    The influences of acute or chronic nicotine pretreatment on ethanol-induced changes on gastric secretion, mucosal blood flow (GMBF), and glandular mucosal damage were studied in anesthetized rats. Ethanol administration decreased gastric acid secretion and GMBF, which were accompanied by a marked increase in gastric mucosal damage. Acute nicotine incubation 2 or 4 mg dose-dependently elevated both the titratable acid in the luminal solution and the gastric secretory volume; it also prevented the depressive action on GMBF and gastric mucosal damage in ethanol-treated animals. Chronic nicotine treatment for 10 days reduced the inhibitory action of ethanol on gastric acid secretion; the higher dose (25 micrograms/ml drinking water) potentiated the decrease of GMBF and the ulcerogenic property of ethanol. However, chronic treatment with the lower dose (5 micrograms/ml drinking water) had the opposite effects; it also markedly increased the gastric secretory volume. It is concluded that acute nicotine pretreatment elevates, whereas chronic nicotine pretreatment differentially affects GMBF. These effects could account for their protective or preventive actions on ethanol ulceration. The increase in nonacid gastric secretory volume by nicotine could partially explain its antiulcer effect. Furthermore, the acid secretory state of the stomach appears unrelated to the ulcerogenic property of ethanol. PMID:2295286

  14. Chronic social isolation during adolescence augments catecholamine response to acute ethanol in the basolateral amygdala.

    PubMed

    Karkhanis, Anushree N; Alexander, Nancy J; McCool, Brian A; Weiner, Jeffrey L; Jones, Sara R

    2015-08-01

    Adolescent social isolation (SI) results in numerous behavioral alterations associated with increased risk of alcoholism. Notably, many of these changes involve the basolateral amygdala (BLA), including increased alcohol seeking. The BLA sends a strong glutamatergic projection to the nucleus accumbens and activation of this pathway potentiates reward-seeking behavior. Dopamine (DA) and norepinephrine (NE) exert powerful excitatory and inhibitory effects on BLA activity and chronic stress can disrupt the excitation-inhibition balance maintained by these catecholamines. Notably, the impact of SI on BLA DA and NE neurotransmission is unknown. Thus the aim of this study was to characterize SI-mediated catecholamine alterations in the BLA. Male Long Evans rats were housed in groups of four (GH) or in SI for 6 weeks during adolescence. DA and NE transporter levels were then measured using Western blot hybridization and baseline and ethanol-stimulated DA and NE levels were quantified using microdialysis. DA transporter levels were increased and baseline DA levels were decreased in SI compared to GH rats. SI also increased DA responses to an acute ethanol (2 g kg(-1)) challenge. While no group differences were noted in NE transporter or baseline NE levels, acute ethanol (2 g kg(-1)) only significantly increased NE levels in SI animals. Collectively, these SI-dependent changes in BLA catecholamine signaling may lead to an increase in BLA excitability and a strengthening of the glutamatergic projection between the BLA and NAc. Such changes may promote the elevated ethanol drinking behavior observed in rats subjected to chronic adolescent stress. PMID:25963724

  15. In vitro anti oxidant activity and acute oral toxicity of Terminalia paniculata bark ethanolic extract on Sprague Dawley rats

    PubMed Central

    Mopuri, Ramgopal; Meriga, Balaji

    2014-01-01

    Objective To ensure the safety and evaluate the anti oxidant activity of Terminalia paniculata (T. paniculata) ethanolic extract in Sprague Dawley rats. Methods The solvent extracts (hexane, ethyl acetate and ethanol) of T. paniculata were subjected to phytochemical analysis and their DPPH radical scavenging activity was assayed. The oral acute toxicity was evaluated using ethanolic extract of T. paniculata. Results Ethyl acetate and ethanolic extracts showed more phytochemicals, whereas highest DPPH scavenging activity was found in ethanolic extract. In an acute toxicity study, T. paniculata ethanolic extract was orally administered (1 000 mg/kg body weight) to rats and observed for 72 h for any toxic symptoms and the dose was continued up to 14 d. On the 15th day rats were sacrificed and blood samples were collected from control and test animals and analyzed for some biochemical parameters. We did not observe any behavioral changes in test groups in comparison with their controls. Also, there were no significant alterations in biochemical, hematological (hemoglobin content and blood cells count) and liver function parameters such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, total proteins, albumin and bilirubin levels between T. paniculata ethanolic extract treated and normal control groups. Conclusions Together our results demonstrated that T. paniculata ethanolic possessed potent antioxidant activity and it was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy. PMID:25182554

  16. Pre-pubertal gonadectomy and the social consequences of acute ethanol in adolescent male and female rats.

    PubMed

    Morales, Melissa; Varlinskaya, Elena I; Spear, Linda P

    2014-07-01

    It has previously been shown that pre-pubertal or adult gonadectomy (GX) increases ethanol intake in male rats. This study examined whether this sex-selective increase reflects a GX-induced maintenance in males of more adolescent-typical responsiveness to ethanol characterized by enhanced sensitivity to positive (e.g., socially facilitating) and a decreased sensitivity to adverse (e.g., socially inhibitory) effects of ethanol. Male and female Sprague-Dawley rats were pre-pubertally GX, sham (SH)-operated, or non-manipulated (NM) at postnatal day (P) 25. During the late adolescent transition into adulthood (P48 - baseline day), rats were given a saline injection, placed alone into a familiar test apparatus for 30min and then exposed for 10min to an unfamiliar partner of the same age and sex. On the following day (P49), similar testing occurred after administration of 0.5, 0.75, 1.0 or 1.25g/kg ethanol. At baseline, GX males and females displayed higher levels of social activity (especially adolescent-typical play and contact behavior) than SH and NM animals, with GX females displaying greater social activity than GX males. Neither males nor females demonstrated social facilitation at lower ethanol doses, regardless of hormonal status. Whereas the social inhibitory effects of higher doses of ethanol were similar across groups among females, SH males were less sensitive than both GX and NM males to ethanol-induced social inhibition. These results suggest that enhanced ethanol intake in GX males is not related to alterations in sensitivity to ethanol's social inhibitory effects. GX, however, results in retention of adolescent-typical social behaviors, with older GX adolescent rats resembling early adolescents in exhibiting elevated social activity-particularly play and contact behavior. PMID:24816080

  17. Microarray characterization of gene expression changes in blood during acute ethanol exposure

    PubMed Central

    2013-01-01

    and hepatic function. Five of the seven clusters showed links to the p38 MAPK pathway. Conclusions The results of this study provide a first look at changing gene expression patterns in human blood during an acute rise in blood ethanol concentration and its depletion because of metabolism and excretion, and demonstrate that it is possible to detect changes in gene expression using total RNA isolated from whole blood. The analysis approach for this study serves as a workflow to investigate the biology linked to expression changes across a time course and from these changes, to identify target genes that could serve as biomarkers linked to pilot performance. PMID:23883607

  18. Adolescent social isolation increases anxiety-like behavior and ethanol intake and impairs fear extinction in adulthood: Possible role of disrupted noradrenergic signaling.

    PubMed

    Skelly, M J; Chappell, A E; Carter, E; Weiner, J L

    2015-10-01

    Alcohol use disorder, anxiety disorders, and post-traumatic stress disorder (PTSD) are highly comorbid, and exposure to chronic stress during adolescence may increase the incidence of these conditions in adulthood. Efforts to identify the common stress-related mechanisms driving these disorders have been hampered, in part, by a lack of reliable preclinical models that replicate their comorbid symptomatology. Prior work by us, and others, has shown that adolescent social isolation increases anxiety-like behaviors and voluntary ethanol consumption in adult male Long-Evans rats. Here we examined whether social isolation also produces deficiencies in extinction of conditioned fear, a hallmark symptom of PTSD. Additionally, as disrupted noradrenergic signaling may contribute to alcoholism, we examined the effect of anxiolytic medications that target noradrenergic signaling on ethanol intake following adolescent social isolation. Our results confirm and extend previous findings that adolescent social isolation increases anxiety-like behavior and enhances ethanol intake and preference in adulthood. Additionally, social isolation is associated with a significant deficit in the extinction of conditioned fear and a marked increase in the ability of noradrenergic therapeutics to decrease ethanol intake. These results suggest that adolescent social isolation not only leads to persistent increases in anxiety-like behaviors and ethanol consumption, but also disrupts fear extinction, and as such may be a useful preclinical model of stress-related psychopathology. Our data also suggest that disrupted noradrenergic signaling may contribute to escalated ethanol drinking following social isolation, thus further highlighting the potential utility of noradrenergic therapeutics in treating the deleterious behavioral sequelae associated with early life stress. PMID:26044636

  19. Effect of ethanol and/or reduced caloric intake during pregnancy on brain weight and synaptic membranes of mothers and their newborn

    SciTech Connect

    Breen, M.; Weinsxein, H.G.

    1986-03-05

    Pregnant female rats were divided into five groups and fed as follows: - Ad libitum (AD), 20% of calories as ethanol (ED20), pair fed to ED20 (CD20), 36% of calories as ethanol (ED36), pair to ED36( CD36). New-born rats were obtained from these groups and labelled:- AN, EN20, CN20, EN36, CN36. The brains were removed and a synaptic membrane enriched fraction isolated which was analyzed for protein, sialic acid and the marker enzymes:- acetylcholinesterase (AC) and Na/K ATPase. Caloric intake was reduced by ethanol to 85% (ED20) and 68% (ED36) of the ad libitum fed (AD). Brain wt. of the neonate was reduced by the lower caloric intake of the dam but ethanol ingestion reduced the brain weight of the neonate even more significantly, CN36 vs. ED36 (p<0.05). The amount of synaptic membranes (syn.mem), in the brain was 5 to 7 times greater in the dam than their corresponding neonates, but there was no significant difference in the sialic acid (SA) content of the syn. mem. of dams and their corresponding neonates; however, the levels of both enzyme markers were negligible in the neonate. The reduced caloric and/or ethanol ingestion by the dam increased the levels of SA in the syn. mem. of both dam and neonate, and the marker enzymes in the dam.

  20. Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions

    PubMed Central

    Cavalcanti-Galdino, M.K.; da Silva, J.A.; Mendes, L.C.; dos Santos, N.A.; Simas, M.L.B.

    2014-01-01

    The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360°. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360° for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360° for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions. PMID:24676473

  1. Oral processing effort, appetite and acute energy intake in lean and obese adults.

    PubMed

    Mattes, Richard D; Considine, Robert V

    2013-08-15

    Chewing reportedly contributes to satiation and satiety signals. Attempts to document and quantify this have led to small and inconsistent effects. The present trial manipulated oral processing effort though required chewing of gums of different hardness and measured appetitive sensations, energy intake, gastric emptying, GI transit time, and concentrations of glucose, insulin, GLP-1, ghrelin and pancreatic polypeptide. Sixty adults classified by sex and BMI (15 each of lean females, obese females, lean males and obese males) were tested in a randomized, controlled, cross-over trial with three arms. They chewed nothing, soft gum or hard gum for 15 min while sipping grape juice (10% of individual energy needs) containing acetaminophen and lactulose on one day each separated by 7 days. Electromyographic recordings and self-reports were obtained during and after chewing to quantify oral processing effort. Blood was sampled through an indwelling catheter and appetite ratings were obtained at baseline and at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min after chewing initiation. Breath samples were collected at 10 min intervals for the first 2h and at 30 min intervals for the next 2h. No effects of chewing were observed for appetitive sensations or gut peptide concentrations. Energy intake tended to decline in lean and increase in obese participants so that daily energy intake differed significantly between the two groups when chewing either gum, while no difference was observed on the non-chewing day. Serum glucose and insulin were significantly lower at selected time points 90-240 min after chewing compared to baseline and the non-chewing day. These data indicate chewing effort does not affect appetitive sensations or gut peptide secretion, but may exert a small differential effect on acute energy intake in lean and obese individuals and lead to greater post-prandial declines of serum glucose and insulin. The efficacy of gum chewing as a substitute for eating for weight

  2. Energy intake and appetite-related hormones following acute aerobic and resistance exercise.

    PubMed

    Balaguera-Cortes, Liliana; Wallman, Karen E; Fairchild, Timothy J; Guelfi, Kym J

    2011-12-01

    Previous research has shown that resistance and aerobic exercise have differing effects on perceived hunger and circulating levels of appetite-related hormones. However, the effect of resistance and aerobic exercise on actual energy intake has never been compared. This study investigated the effect of an acute bout of resistance exercise, compared with aerobic exercise, on subsequent energy intake and appetite-regulating hormones. Ten active men completed 3 trials in a counterbalanced design: 45 min of resistance exercise (RES; free and machine weights), aerobic exercise (AER; running), or a resting control trial (CON). Following exercise or CON, participants had access to a buffet-style array of breakfast foods and drinks to consume ad libitum. Plasma concentrations of a range of appetite-regulating hormones were measured throughout each trial. Despite significantly higher energy expenditure with AER compared with RES (p < 0.05), there was no difference in total energy intake from the postexercise meal between trials (p = 0.779). Pancreatic polypeptide was significantly higher prior to the meal after both RES and AER compared with CON. In contrast, active ghrelin was lower following RES compared with both CON and AER (p ≤ 0.05), while insulin was higher following RES compared with CON (p = 0.013). In summary, the differential response of appetite-regulating hormones to AER and RES does not appear to influence energy intake in the postexercise meal. However, given the greater energy expenditure associated with AER compared with RES, AER modes of exercise may be preferable for achieving short-term negative energy balance. PMID:22111518

  3. INCREASES IN ANXIETY-LIKE BEHAVIOR INDUCED BY ACUTE STRESS ARE REVERSED BY ETHANOL IN ADOLESCENT BUT NOT ADULT RATS

    PubMed Central

    Varlinskaya, Elena I.; Spear, Linda P.

    2011-01-01

    Repeated exposure to stressors has been found to increase anxiety-like behavior in laboratory rodents, with the social anxiety induced by repeated restraint being extremely sensitive to anxiolytic effects of ethanol in both adolescent and adult rats. No studies, however, have compared social anxiogenic effects of acute stress or the capacity of ethanol to reverse this anxiety in adolescent and adult animals. Therefore, the present study was designed to investigate whether adolescent [postnatal day (P35)] Sprague-Dawley rats differ from their adult counterparts (P70) in the impact of acute restraint stress on social anxiety and in their sensitivity to the social anxiolytic effects of ethanol. Animals were restrained for 90 min, followed by examination of stress- and ethanol-induced (0, 0.25, 0.5, 0.75, and 1 g/kg) alterations in social behavior using a modified social interaction test in a familiar environment. Acute restraint stress increased anxiety, as indexed by reduced levels of social investigation at both ages, and decreased social preference among adolescents. These increases in anxiety were dramatically reversed among adolescents by acute ethanol. No anxiolytic-like effects of ethanol emerged following restraint stress in adults. The social suppression seen in response to higher doses of ethanol was reversed by restraint stress in animals of both ages. To the extent that these data are applicable to humans, the results of the present study provide some experimental evidence that stressful life events may increase the attractiveness of alcohol as an anxiolytic agent for adolescents. PMID:22024161

  4. [Two cases of acute coronary syndrome after intake of Clavis Panax].

    PubMed

    Atar, Aslı İnci; Er, Okan; Güven, Abdullah; Eryonucu, Beyhan

    2012-04-01

    Atherosclerotic cardiovascular disease is an epidemic in today's world. It is one of the most common causes of hospitalization and death. Therefore, remedies to control or heal the disease are continuously sought. In addition to scientifically researched therapies, patients frequently utilize alternative medicine. However, effective and toxic doses, metabolisms, and drug interactions of the herbs and herbal nutrition supplements are largely unknown. Herein, we present two cases with acute coronary syndrome. The first case was admitted with a diagnosis of acute inferior myocardial infaction (MI) and a stent was implanted to the occluded right coronary artery (RCA). There was a 50% stenosis in his left anterior descending artery (LAD). He was admitted with a diagnosis of non-ST elevation MI (NSTEMI) 6 months later. In the coronary angiogram, there was stent restenosis in RCA, the lesion in LAD had become thrombotic and progressed to a stenosis of 90%. He was referred to surgical revascularization. The second case was admitted for acute inferior MI and a stent was implanted to the occluded circumflex artery. Two months later, he was hospitalized for NSTEMI. Progression of coronary plaques to stenosis and stent restenosis was detected and he was referred to surgical revascularization. Both patients used the product sold as Clavis Panax, which contains panax ginseng, tribulus terrestris, and oat, after their first coronary intervention. Intake of a mixture of plant extracts may have serious consequences in humans as drug interactions and side effects are unknown. PMID:22864326

  5. Male sexual behaviour and ethanol consumption from an evolutionary perspective: A comment on “Sexual Deprivation Increases Ethanol Intake in Drosophila”

    PubMed Central

    2014-01-01

    Shohat-Ophir et al.1 demonstrate a connection between sexual behaviour and ethanol consumption in male Drosophila flies, and how the neuropeptide F system regulates ethanol preference. Their results are rightly discussed only in a physiological context, but this has facilitated erroneous anthropomorphic interpretations by the media. Here we discuss the link between male sexual behaviour and ethanol consumption from an evolutionary perspective, providing a broader context to interpret their results. PMID:25970263

  6. Effects of Amoxicillin and Augmentin on Cystine-Glutamate Exchanger and Glutamate Transporter 1 Isoforms as well as Ethanol Intake in Alcohol-Preferring Rats.

    PubMed

    Hakami, Alqassem Y; Hammad, Alaa M; Sari, Youssef

    2016-01-01

    Alcohol dependence is associated with alteration of glutamate transport and glutamate neurotransmission. Glutamate transporter 1 (GLT-1) is a major transporter that regulates the majority of extracellular glutamate concentration, which is also regulated by cystine-glutamate exchanger (xCT). Importantly, we recently reported that amoxicillin and Augmentin (amoxicillin/clavulanate) upreglulated GLT-1 expression in nucleus accumbens (NAc) and prefrontal cortex (PFC) as well as reduced ethanol consumption in male P rats. In this study, we examined the effects of amoxicillin and Augmentin on GLT-1 isoforms (GLT-1a and GLT-1b), xCT, and glutamate/aspartate transporter (GLAST) expression in NAc and PFC as well as ethanol intake in male P rats. We found that both compounds significantly reduced ethanol intake, and increased GLT-1a, GLT-1b, and xCT expression in NAc. However, only Augmentin increased GLT-1a, GLT-1b, and xCT expression in PFC. There were no effects of these compounds on GLAST expression in NAc and PFC. These findings demonstrated that Augmentin and amoxicillin have the potential to upregulate GLT-1 isoforms and xCT expression, and consequently attenuate ethanol dependence. PMID:27199635

  7. Effects of Amoxicillin and Augmentin on Cystine-Glutamate Exchanger and Glutamate Transporter 1 Isoforms as well as Ethanol Intake in Alcohol-Preferring Rats

    PubMed Central

    Hakami, Alqassem Y.; Hammad, Alaa M.; Sari, Youssef

    2016-01-01

    Alcohol dependence is associated with alteration of glutamate transport and glutamate neurotransmission. Glutamate transporter 1 (GLT-1) is a major transporter that regulates the majority of extracellular glutamate concentration, which is also regulated by cystine-glutamate exchanger (xCT). Importantly, we recently reported that amoxicillin and Augmentin (amoxicillin/clavulanate) upreglulated GLT-1 expression in nucleus accumbens (NAc) and prefrontal cortex (PFC) as well as reduced ethanol consumption in male P rats. In this study, we examined the effects of amoxicillin and Augmentin on GLT-1 isoforms (GLT-1a and GLT-1b), xCT, and glutamate/aspartate transporter (GLAST) expression in NAc and PFC as well as ethanol intake in male P rats. We found that both compounds significantly reduced ethanol intake, and increased GLT-1a, GLT-1b, and xCT expression in NAc. However, only Augmentin increased GLT-1a, GLT-1b, and xCT expression in PFC. There were no effects of these compounds on GLAST expression in NAc and PFC. These findings demonstrated that Augmentin and amoxicillin have the potential to upregulate GLT-1 isoforms and xCT expression, and consequently attenuate ethanol dependence. PMID:27199635

  8. Autonomous system for cross-organ investigation of ethanol-induced acute response in behaving larval zebrafish.

    PubMed

    Lin, Xudong; Li, Vincent W T; Chen, Siya; Chan, Chung-Yuen; Cheng, Shuk-Han; Shi, Peng

    2016-03-01

    Ethanol is widely consumed and has been associated with various diseases in different organs. It is therefore important to study ethanol-induced responses in living organisms with the capability to address specific organs in an integrative manner. Here, we developed an autonomous system based on a series of microfluidic chips for cross-organ investigation of ethanol-induced acute response in behaving larval zebrafish. This system enabled high-throughput, gel-free, and anesthetic-free manipulation of larvae, and thus allowed real-time observation of behavioral responses, and associated physiological changes at cellular resolution within specific organs in response to acute ethanol stimuli, which would otherwise be impossible by using traditional methods for larva immobilization and orientation. Specifically, three types of chips ("motion," "lateral," and "dorsal"), based on a simple hydrodynamic design, were used to perform analysis in animal behavior, cardiac, and brain physiology, respectively. We found that ethanol affected larval zebrafish in a dose-dependent manner. The motor function of different body parts was significantly modulated by ethanol treatment, especially at a high dose of 3%. These behavioral changes were temporally associated with a slow-down of heart-beating and a stereotyped activation of certain brain regions. As we demonstrated in this proof-of-concept study, this versatile Fish-on-Chip platform could potentially be adopted for systematic cross-organ investigations involving chemical or genetic manipulations in zebrafish model. PMID:27158291

  9. The influence of chronic or acute nicotine pretreatment on ethanol-induced gastric ulceration in the rat.

    PubMed

    Wong, S H; Ogle, C W; Cho, C H

    1986-07-01

    The effects in rats of chronic or acute nicotine pretreatment were studied on three gastric parameters: ethanol-induced ulceration, gastric wall mucus content and gastric acid secretion, under basal or histamine-stimulated conditions. Oral administration of ethanol (40%, 10 ml kg-1) depleted gastric wall mucus and produced ulceration in the gastric glandular mucosa. Ten-day nicotine pretreatment (15 or 25 micrograms ml-1 drinking water) worsened the adverse effects of ethanol on mucosal ulceration and mucus content, potentiated the gastric secretory action of histamine, but did not affect basal acid secretion. Single oral doses of nicotine (2 or 4 mg kg-1, given 1 h beforehand) prevented ulceration and mucus depletion in ethanol-treated animals; however, they did not influence either basal or histamine-stimulated gastric acid output. It is concluded that chronic nicotine administration aggravates ethanol ulceration, possibly by decreasing gastric wall mucus content and sensitizing the stomach to the acid secretory action of histamine. On the other hand, an acute oral dose of nicotine preserves the mucus content and prevents ethanol-induced ulcer formation. PMID:2427681

  10. Acute arrhythmogenesis after myocardial infarction in normotensive rats: influence of high salt intake.

    PubMed

    Baldo, Marcelo Perim; Teixeira, Anna Késia Guerrat; Rodrigues, Sérgio Lamêgo; Mill, José Geraldo

    2012-03-01

    A high salt diet is a known risk factor for cardiovascular diseases that leads to cardiac hypertrophy and creates a substrate for arrhythmias and sudden death. However, acute arrhythmogenesis after infarction has not been studied. Male Wistar rats (21 days) received drinking water (MI) or 1% NaCl solution (MI-Salt-C) for 4 weeks. Water was given to another group for 4 weeks, and on the day before surgery, animals received a 1% NaCl solution (MI-Salt-A). Non-invasive systolic blood pressure (SBP) was obtained before surgery. Myocardial infarction (MI) was produced by permanent occlusion of the left coronary artery. Electrocardiogram was monitored during the first 30 min post-occlusion to evaluate arrhythmias. Although SBP was not altered by salt intake (SHAM: 114±2, MI: 112±2, MI-Salt-C: 115±2, MI-Salt-A: 116±4 mm Hg), ventricular hypertrophy was observed in the animals receiving chronic salt diet (SHAM: 0.22±0.008, MI: 0.23±0.007, MI-Salt-C: 0.28±0.01; MI-Salt-A: 0.23±0.01 g/cm; P<0.05). Ventricular premature beats increased in both salt-loaded groups compared to MI group (MI: 805±81, MI-Salt-C: 1145±98; MI-Salt-A: 1023±77; P<0.05). Atrioventricular blockade was only observed in animals subjected to high salt intake (MI-Salt-C: 38.9%; MI-Salt-A: 42.1%). High salt intake was associated with increased post-infarct arrhythmias; however, this effect was unrelated to ventricular hypertrophy. PMID:22142697

  11. Large-Scale Analysis of Acute Ethanol Exposure in Zebrafish Development: A Critical Time Window and Resilience

    PubMed Central

    Ali, Shaukat; Champagne, Danielle L.; Alia, Alia; Richardson, Michael K.

    2011-01-01

    Background In humans, ethanol exposure during pregnancy causes a spectrum of developmental defects (fetal alcohol syndrome or FAS). Individuals vary in phenotypic expression. Zebrafish embryos develop FAS-like features after ethanol exposure. In this study, we ask whether stage-specific effects of ethanol can be identified in the zebrafish, and if so, whether they allow the pinpointing of sensitive developmental mechanisms. We have therefore conducted the first large-scale (>1500 embryos) analysis of acute, stage-specific drug effects on zebrafish development, with a large panel of readouts. Methodology/Principal Findings Zebrafish embryos were raised in 96-well plates. Range-finding indicated that 10% ethanol for 1 h was suitable for an acute exposure regime. High-resolution magic-angle spinning proton magnetic resonance spectroscopy showed that this produced a transient pulse of 0.86% concentration of ethanol in the embryo within the chorion. Survivors at 5 days postfertilisation were analysed. Phenotypes ranged from normal (resilient) to severely malformed. Ethanol exposure at early stages caused high mortality (≥88%). At later stages of exposure, mortality declined and malformations developed. Pharyngeal arch hypoplasia and behavioral impairment were most common after prim-6 and prim-16 exposure. By contrast, microphthalmia and growth retardation were stage-independent. Conclusions Our findings show that some ethanol effects are strongly stage-dependent. The phenotypes mimic key aspects of FAS including craniofacial abnormality, microphthalmia, growth retardation and behavioral impairment. We also identify a critical time window (prim-6 and prim-16) for ethanol sensitivity. Finally, our identification of a wide phenotypic spectrum is reminiscent of human FAS, and may provide a useful model for studying disease resilience. PMID:21625530

  12. Differential effects of naltrexone on cardiac, subjective and behavioural reactions to acute ethanol intoxication

    PubMed Central

    Peterson, Jordan B.; Conrod, Patricia; Vassileva, Jasmin; Gianoulakis, Christina; Pihl, Robert O.

    2006-01-01

    Objective Alcohol may have psychomotor stimulant properties during the rising limb of the blood alcohol curve at commonly self-administered doses. Increased heart rate (HR) immediately after alcohol consumption may serve as an indicator or marker of such properties, which appear to be potentially opiate-mediated and dopamine-dependent. Naltrexone, an opiate antagonist, has been used successfully in the treatment of alcoholism and may produce its therapeutic effects through its effects on alcohol metabolism or by blocking alcohol's rewarding effects. We hypothesized that, if naltrexone blocks the psychomotor stimulant properties of ethanol, then it would decrease or eliminate the HR increase associated with acute alcohol intoxication and that this would be independent of any effect on alcohol metabolism. Methods Twenty male subjects were administered placebo and alcohol (1.0 mL 95% USP ethanol/kg body weight) in a laboratory setting on one day and naltrexone (50 mg) and alcohol on another (counterbalanced). We assessed all subjects for a change in HR and for a subjective and behavioural response from 35 to 170 minutes after drug or alcohol administration. Results The placebo and alcohol mix produced a significant mean HR increase from baseline (F1,95 = 46.01, p < 0.0001, Cohen's d = 0.62), while naltrexone and alcohol did not (nonsignificant). The significant effects of naltrexone on blood alcohol level did not account for the effect of naltrexone on alcohol-induced HR change but did account for alterations in subjective and behavioural response to alcohol. Conclusions Naltrexone appears to substantially reduce the HR increase that is characteristic of alcohol intoxication. This finding appears to lend moderate support to the notions that, first, naltrexone has differential effects on alcohol reactions and, second, that it specifically blocks the acute psychomotor stimulant properties of alcohol. PMID:17136216

  13. Changes in sleep, food intake, and activity levels during acute painful episodes in children with sickle cell disease.

    PubMed

    Jacob, Eufemia; Miaskowski, Christine; Savedra, Marilyn; Beyer, Judith E; Treadwell, Marsha; Styles, Lori

    2006-02-01

    As part of a larger study that examined pain experience, pain management, and pain outcomes among children with sickle cell disease, functional status (sleep, food intake, and activity levels) was examined during hospitalization for acute painful episodes. Children were asked to rate the amount of pain they experienced as well as the amount of time they slept, the amount of food they ate, and the amount of activity they had everyday. Children reported high levels of pain, which showed only a small decrease throughout hospitalization, and had disrupted sleep and wake patterns, decreased food intake, and decreased activity levels. Nurses need to routinely monitor functional status during acute painful episodes so that strategies to promote adequate sleep, food intake, and activity may be incorporated to minimize long-term negative outcomes in children with sickle cell disease. PMID:16428011

  14. Hepatoprotective effect of carob against acute ethanol-induced oxidative stress in rat.

    PubMed

    Souli, Abdelaziz; Sebai, Hichem; Chehimi, Latifa; Rtibi, Kaïs; Tounsi, Haifa; Boubaker, Samir; Sakly, Mohsen; El-Benna, Jamel; Amri, Mohamed

    2015-09-01

    The present study was undertaken to determine whether subacute treatment with aqueous extract of carob (Ceratonia siliqua L.) pods (AECPs) protects against ethanol (EtOH)-induced oxidative stress in rat liver. Animals were divided into four groups: control, carob, EtOH and EtOH + carob. Wistar rats were intraperitoneally pretreated with AECP (600 mg/kg body weight (bw)) during 7 days and intoxicated for 6 h by acute oral administration of EtOH (6 g/kg bw) 24 h after the last injection. We found that acute administration of EtOH leads to hepatotoxicity as monitored by the increase in the levels of hepatic marker aspartate aminotransferase and alanine aminotransferase as well as hepatic tissue injury. EtOH also increased the formation of malondialdehyde in the liver, indicating an increase in lipid peroxidation and depletion of antioxidant enzyme activities as superoxide dismutase, catalase and glutathione peroxidase. Subacute carob pretreatment prevented all the alterations induced by EtOH and returned their levels to near normal. Importantly, we showed that acute alcohol increased hepatic and plasmatic hydrogen peroxide and free iron levels. The carob pretreatment reversed EtOH effects to near control levels. These data suggest that carob could have a beneficial effect in inhibiting the oxidative damage induced by acute EtOH administration and that its mode of action may involve an opposite effect on plasma and tissue-free iron accumulation. Indeed, carob can be offered as a food additive to protect against EtOH-induced oxidative damage. PMID:23363576

  15. Plasma and Urinary Phenolic Profiles after Acute and Repetitive Intake of Wild Blueberry.

    PubMed

    Feliciano, Rodrigo P; Istas, Geoffrey; Heiss, Christian; Rodriguez-Mateos, Ana

    2016-01-01

    Recent studies have shown that blueberries may have cardiovascular and cognitive health benefits. In this work, we investigated the profile of plasma and urine (poly)phenol metabolites after acute and daily consumption of wild blueberries for 30 days in 18 healthy men. The inter-individual variability in plasma and urinary polyphenol levels was also investigated. Blood samples were collected at baseline and 2 h post-consumption on day 1 and day 30. Twenty-four-hour urine was also collected on both days. A total of 61 phenolic metabolites were quantified in plasma at baseline, of which 43 increased after acute or chronic consumption of blueberries over one month. Benzoic and catechol derivatives represented more than 80% of the changes in phenolic profile after 2 h consumption on day 1, whereas hippuric and benzoic derivatives were the major compounds that increased at 0 and 2 h on day 30, respectively. The total (poly)phenol urinary excretion remained unchanged after 30 days of wild blueberry intake. The inter-individual variability ranged between 40%-48% in plasma and 47%-54% in urine. Taken together, our results illustrate that blueberry (poly)phenols are absorbed and extensively metabolized by phase II enzymes and by the gut microbiota, leading to a whole array of metabolites that may be responsible for the beneficial effects observed after blueberry consumption. PMID:27571052

  16. Fatty acid ethyl esters in hair: correlation with self-reported ethanol intake in 160 subjects and influence of estroprogestin therapy.

    PubMed

    Bertol, Elisabetta; Del Bravo, Ester; Vaiano, Fabio; Mari, Francesco; Favretto, Donata

    2014-09-01

    Fatty acid ethyl esters (FAEEs) are minor ethanol metabolites that can accumulate in hair. The performance of hair FAEEs as a biomarker that can discriminate null or moderate drinking from risky, excessive drinking was verified by evaluating the relationship between self-reported daily alcohol intake and FAEE concentration in hair. The study subjects were 160 healthy volunteers (52% female) that included teetotallers, moderate/social drinkers (< 60 g of ethanol per day), and heavy drinkers (≥ 60 g/day).The estimated daily alcohol intake (EDAI) was assessed by a specific written questionnaire aimed at estimating the measure and the frequency of alcohol drinking and at excluding confounding factors. FAEEs (ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate) were extracted from the hair matrix by overnight incubation in n-hexane/dimethylsulphoxide, purified by solid-phase extraction (SPE) and analyzed by gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring and Electron ionization (EI) mode, using pentadeuterated internal standards. Hair samples exhibited FAEE concentrations (expressed as the sum of the four esters, CFAEE ) ranging from 0.01 to 10.78 ng/mg (average 1.16 and median 0.60 ng/mg). The EDAI was from 0 to 246 g of ethanol per day, average 28 g/day and median 15 g/day. A cut-off of 0.5 ng/mg in 3 cm of a proximal hair segment was adopted to discriminate social drinking from excessive ethanol consumption. False positive samples were identified in subjects using ethanol-containing hair lotions and women on estroprogestin therapy. Specificity of 87% was reached when the identified false positives were excluded from data elaboration. CFAEE in hair at a predetermined cut-off can be used to discriminate between moderate and excessive drinking only when confounding factors are meticulously removed. PMID:24431044

  17. The involvement of NMDA receptors in acute and chronic effects of ethanol.

    PubMed

    Danysz, W; Dyr, W; Jankowska, E; Glazewski, S; Kostowski, W

    1992-06-01

    Recent evidence indicates involvement of excitatory amino acid receptors sensitive to N-methyl-d-aspartate (NMDA) in the action of ethanol (EtOH). Pronounced inhibition of NMDA receptor function is seen in vitro with concentrations of EtOH corresponding to those present during alcohol intoxication in humans. The present study was devoted to investigate the role of NMDA receptors in the action of EtOH in rats. Acute experiments showed antagonism by EtOH of convulsions induced by intracerebroventricular injection of NMDA. A similar effect was seen with a high dose of diazepam. Convulsions induced by an agonist of another excitatory amino acid receptor subtype, kainate, were also inhibited by EtOH. An uncompetitive antagonist of NMDA receptors, 5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate (MK-801), potentiated EtOH-induced loss of righting, but attenuated the hypothermic action of EtOH. Moreover, MK-801 inhibited audiogenic convulsions in EtOH withdrawn rats. At the same time the effect of a proconvulsive dose of NMDA was not enhanced. Tolerance to the myorelaxant action of both EtOH and MK-801 upon repetitive administration was seen. Also some degree of cross-tolerance was observed. Moreover, MK-801 failed to modify EtOH preference in rats. The present results support involvement of NMDA receptors in expression of some acute and subchronic actions of EtOH and in expression of EtOH withdrawal. PMID:1385679

  18. Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents I. Validation of methods with ethanol.

    PubMed

    McKee, R H; Lammers, J H C M; Hoogendijk, E M G; Emmen, H H; Muijser, H; Barsotti, D A; Owen, D E; Kulig, B M

    2006-12-01

    As a preliminary step to evaluating the acute neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, joint neurobehavioral/toxicokinetic studies were conducted which involved administering ethanol to rats and volunteers. The specific objectives of the present studies were to evaluate the acute central nervous system (CNS) effects of ethanol in rats and humans and to assess relationships between internal levels of exposure and behavioral effects. A more general objective was to validate a battery of neurobehavioral tests that could be used to carry out comparative studies in both species. Accordingly, a range of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute CNS effects. Groups of rats were given ethanol at levels of approximately 0.5, 1.0 or 2.0g/kg, with blood level measurements to verify internal doses. In a volunteer study, 12 healthy male subjects were given 0.65g/kg ethanol, a level approximating the limit for motor vehicle operation in The Netherlands, and neurobehavioral effects were measured prior to and 1 and 3h after ethanol administration, with a computerized neurobehavioral test battery. Blood and air measurements were made to quantify internal doses. Results of the behavioral tests in rats provided evidence of ethanol-induced changes in neuromuscular, sensori-motor, and activity domains. There were also significant changes in visual discrimination, particularly in the areas of general measures of responding and psychomotor speed. In humans there were small but statistically significant effects on learning and memory, psychomotor skills and attention. However, the effects were subtle and not all parameters within given domains were affected. These studies demonstrated a qualitative similarity in response between rats and humans. PMID:16831461

  19. Effects of cigarette smoke and ethanol intake on mouse oesophageal mucosa changes induced by dietary zinc deficiency and deoxycholic acid supplementation.

    PubMed

    Zapaterini, Joyce R; de Moura, Nelci A; Ribeiro, Daniel A; Rodrigues, Maria A M; Barbisan, Luis F

    2012-08-01

    The noxious effects of dietary zinc deficiency (ZD) and deoxycholic bile acid (DCA) supplementation in the oesophagus were investigated. The additional influence of cigarette smoke and ethanol intake on the changes in the oesophageal mucosa induced by dietary ZD plus DCA was also assessed. Male C57BL/6 mice were allocated into four groups: Group 1 was fed control diet and groups 2-4 were fed ZD plus DCA diet. After 5 weeks, groups 3 and 4 were exposed to 10% ethanol intake or cigarette smoke for 15 weeks, respectively. All animals were euthanized at the end of week 20, and the oesophagus, lung, liver and colon were collected and analysed by conventional morphology. Cell proliferation was assessed in the oesophageal mucosa by Ki-67 immunohistochemistry and cyclooxygenase 2 (COX-2) protein by Western blotting. Dietary ZD plus DCA treatment induced mild hyperkeratosis and hyperplasia, increased cell proliferation index and COX-2 protein expression in the oesophagus, and intranuclear inclusion, karyocytomegaly and microvesicular fatty change in the liver. Cigarette smoke increased COX-2 protein expression in oesophageal mucosa and irregular enlargement of alveolus and alveolar ductal air spaces, while ethanol enhanced liver damage induced by ZD plus DCA diet. These findings indicate that dietary ZD plus DCA treatment during 20 weeks induces a pattern of chemical oesophageal injury but not Barrett's-like lesions. PMID:22380924

  20. Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol.

    PubMed

    Suryanarayanan, A; Carter, J M; Landin, J D; Morrow, A L; Werner, D F; Spigelman, I

    2016-08-01

    Mounting evidence indicates that ethanol (EtOH) exposure activates neuroimmune signaling. Alterations in pro-inflammatory cytokines after acute and chronic EtOH exposure have been heavily investigated. In contrast, little is known about the regulation of neurotransmission and/or modulation by anti-inflammatory cytokines in the brain after an acute EtOH exposure. Recent evidence suggests that interleukin-10 (IL-10), an anti-inflammatory cytokine, is upregulated during withdrawal from chronic EtOH exposure. In the present study, we show that IL-10 is increased early (1 h) after a single intoxicating dose of EtOH (5 g/kg, intragastric) in Sprague Dawley rats. We also show that IL-10 rapidly regulates GABAergic transmission in dentate gyrus neurons. In brain slice recordings, IL-10 application dose-dependently decreases miniature inhibitory postsynaptic current (mIPSC) area and frequency, and decreases the magnitude of the picrotoxin sensitive tonic current (Itonic), indicating both pre- and postsynaptic mechanisms. A PI3K inhibitor LY294002 (but not the negative control LY303511) ablated the inhibitory effects of IL-10 on mIPSC area and Itonic, but not on mIPSC frequency, indicating the involvement of PI3K in postsynaptic effects of IL-10 on GABAergic transmission. Lastly, we also identify a novel neurobehavioral regulation of EtOH sensitivity by IL-10, whereby IL-10 attenuates acute EtOH-induced hypnosis. These results suggest that EtOH causes an early release of IL-10 in the brain, which may contribute to neuronal hyperexcitability as well as disturbed sleep seen after binge exposure to EtOH. These results also identify IL-10 signaling as a potential therapeutic target in alcohol-use disorders and other CNS disorders where GABAergic transmission is altered. PMID:27016017

  1. Lithium clearance in man: effects of dietary salt intake, acute changes in extracellular fluid volume, amiloride and frusemide.

    PubMed

    Atherton, J C; Green, R; Hughes, S; McFall, V; Sharples, J A; Solomon, L R; Wilson, L

    1987-12-01

    1. The effects of amiloride and frusemide on lithium clearance were studied during changes in dietary sodium chloride intake and during infusion of 0.9% NaCl in normal human volunteers. 2. Lithium and fractional lithium clearances were less on the low than on the high salt diet. Values for the medium salt diet were intermediate. Acute extracellular fluid volume expansion with 0.9% NaCl infusion and extracellular fluid volume contraction 3-4 h after intravenous frusemide caused lithium and fractional lithium clearances to increase and decrease respectively. 3. Amiloride caused small changes in lithium and fractional lithium clearances on a low salt diet, but was without effect when salt intake was medium or high. 4. Increases in lithium clearance occurred immediately after frusemide irrespective of dietary salt intake and in subjects infused with 0.9% NaCl. Only in salt-depleted subjects did frusemide cause a substantial increase in fractional lithium clearance. Changes induced under other circumstances were small. 5. It is concluded that the lithium clearance method for assessment of proximal tubule salt and water reabsorption can be used with some degree of confidence in certain circumstances (medium and high salt intake as well as in acute volume expansion) but may not be reliable when dietary salt intake is low. PMID:3690979

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

    PubMed Central

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

    2015-01-01

    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. PMID:26628398

  3. 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. PMID:26628398

  4. Protective effect of panax notoginseng saponins on acute ethanol-induced liver injury is associated with ameliorating hepatic lipid accumulation and reducing ethanol-mediated oxidative stress.

    PubMed

    Ding, Ren-Bo; Tian, Ke; Cao, Yi-Wei; Bao, Jiao-Lin; Wang, Meng; He, Chengwei; Hu, Yuanjia; Su, Huanxing; Wan, Jian-Bo

    2015-03-11

    The aim of present study was to evaluate the effects of Panax notoginseng saponins (PNS) against acute ethanol-induced liver injury and further to elucidate its probable mechanisms. Mice were treated with PNS (100 or 300 mg/kg) once daily for seven consecutive days priors to ethanol gavage (4.7 g/kg) every 12 h for a total of three doses. Acute alcohol gavage dramatically significantly increased serum activities of alanine aminotransferase (ALT) (23.4 ± 5.0 IU/L vs 11.7 ± 4.1 IU/L) and aspartate aminotransferase (AST) (52.6 ± 14.9 IU/L vs 31.1 ± 12.9 IU/L), and hepatic triglyceride level (4.04 ± 0.64 mg/g vs 1.92 ± 0.34 mg/g), these elevations were significantly diminished by pretreatment with PNS at dose of 100 mg/kg or 300 mg/kg. Alcohol exposure markedly induced the lipolysis of white adipose tissue (WAT), up-regulated protein expression of the phosphorylated hormone-sensitive lipase (p-HSL, p < 0.01), and total HSL (p < 0.01), and enhanced fatty acid uptake capacity in liver as indicated by increasing hepatic CD36 expression (p < 0.01), these effects were attenuated by PNS treatment. Additionally, PNS suppressed the elevation of reactive oxygen species (ROS) production and malondialdehyde (MDA) content, reduced TNF-α and IL-6 levels, restored glutathione (GSH) level, enhanced the superoxide dismutase (SOD) activity in liver, and abrogated cytochrome P450 2E1 (CYP2E1) induction. These data demonstrated that pretreatment with PNS protected against acute ethanol-induced liver injury, possibly through ameliorating hepatic lipid accumulation and reducing CYP2E1-mediated oxidative stress. Our findings also suggested that PNS may be potential to be developed as an effective agent for acute ethanol-induced liver injury. PMID:25665731

  5. Effect of acute and chronic ethanol pre-treatment on the disposition of phencyclidine (PCP) in the rat.

    PubMed

    Vadlamani, N L; Pontani, R B; Misra, A L

    1982-05-01

    Disposition of [H] Phencyclidine in brain, plasma and adipose tissue of rats acutely and chronically-treated with ethanol was studied using a method possessing high sensitivity and specificity for PCP. In rats acutely-treated with ethanol (5 g/kg PO dose) and PCP (10 mg/kg IP dose), dispositional factors did not play a role in the intensifies pharmacological and behavioral effects of PCP. However in rats chronically-treated with 2.5 g/kg PO dose of ethanol twice a day for 19 days, the disposition of PCP (5 mg/kg IP dose) was significantly altered and the values of PCP in brain, plasma and adipose tissue were significantly higher than those in the control group. Although inhibition of PCP metabolism and a comparatively slower rate of its elimination appear to account for the potentiation of drug effects in animals chronically-treated with ethanol, interaction of drugs at the level of the central nervous system cannot be ruled out. PMID:7089042

  6. Effects of acute ethanol exposure on cytokine production by primary airway smooth muscle cells.

    PubMed

    Kaphalia, Lata; Kalita, Mridul; Kaphalia, Bhupendra S; Calhoun, William J

    2016-02-01

    Both chronic and binge alcohol abuse can be significant risk factors for inflammatory lung diseases such as acute respiratory distress syndrome and chronic obstructive pulmonary disease. However, metabolic basis of alcohol-related lung disease is not well defined, and may include key metabolites of ethanol [EtOH] in addition to EtOH itself. Therefore, we investigated the effects of EtOH, acetaldehyde [ACE], and fatty acid ethyl esters [FAEEs] on oxidative stress, endoplasmic reticulum (ER) stress, AMP-activated protein kinase (AMPK) signaling and nuclear translocation of phosphorylated (p)-NF-κB p65 in primary human airway smooth muscle (HASM) cells stimulated to produce cytokines using LPS exposure. Both FAEEs and ACE induced evidence of cellular oxidative stress and ER stress, and increased p-NF-κB in nuclear extracts. EtOH and its metabolites decreased p-AMPKα activation, and induced expression of fatty acid synthase, and decreased expression of sirtuin 1. In general, EtOH decreased secretion of IP-10, IL-6, eotaxin, GCSF, and MCP-1. However, FAEEs and ACE increased these cytokines, suggesting that both FAEEs and ACE as compared to EtOH itself are proinflammatory. A direct effect of EtOH could be consistent with blunted immune response. Collectively, these two features of EtOH exposure, coupled with the known inhibition of innate immune response in our model might explain some clinical manifestations of EtOH exposure in the lung. PMID:26721307

  7. 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

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

    2016-03-01

    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

  8. Comparative study of the damage produced by acute ethanol and acetaldehyde treatment in a human fetal hepatic cell line.

    PubMed

    Olivares, I P; Bucio, L; Souza, V; Cárabez, A; Gutiérrez-Ruiz, M C

    1997-06-27

    The effects of acute ethanol and acetaldehyde treatment on cell proliferation, cell adhesion capacity, neutral red incorporation into lysosomes, glutathione content, protein sulfhydryl compounds, lipid peroxidation, inner mitochondrial membrane integrity (MTT test), lactate dehydrogenase activity (LDH) and ultrastructural alterations were investigated in a human fetal hepatic cell line (WRL-68 cells). WRL-68 cells were used, due to the fact that, although this cell line expresses some hepatic characteristics, it does not express alcohol dehydrogenase or cytochrome P450 activity, so it could be a good model to study the effect of the toxic agents per se. Cells were exposed during 120 min with 200 mM ethanol or 10 mM acetaldehyde. Under these conditions, cells presented 100% viability and no morphological alteration was observed by light microscopy. Acetaldehyde-treated cells reduced their proliferative capacity drastically while the ethanol-treated ones presented no difference with control cells. Cell adhesion to substrate, measured as time required to adhere to the substrate and time required to detach from the substrate, was diminished in acetaldehyde WRL-68-treated cells. Cytotoxicity measures as neutral red and MTT test showed that acetaldehyde-treated cells presented more damage than ethanol-treated ones. Cellular respiratory capacity was compromised by acetaldehyde treatment due to 40% less oxygen consumption than control cells. Lipid peroxidation values, measured as malondialdehyde production, were higher in ethanol-treated WRL-68 cells (127%) than in acetaldehyde-treated ones (60%) to control cell values. Lactate dehydrogenase activity (LDH) in extracellular media of ethanol-treated cells presented the highest values. GSH content was reduced 95% and thiol protein content was diminished severely in acetaldehyde-treated cells. Transmission electron microscopy showed more ultrastructural alterations in cells treated with acetaldehyde. The results indicate that

  9. Potential factors associated with fruit and vegetable intake after premature acute coronary syndrome: a prospective cohort study.

    PubMed

    Leung Yinko, Sylvie S L; Pelletier, Roxanne; Behlouli, Hassan; Bacon, Simon L; Karp, Igor; Thanassoulis, George; Daskalopoulou, Stella S; Eisenberg, Mark J; Khan, Nadia A; Lavoie, Kim L; Pilote, Louise

    2015-01-01

    Studies on dietary changes and their associated factors are limited, particularly with respect to younger cardiovascular patients. Our objective was to evaluate the factors associated with fruit and vegetable intake among adults with premature acute coronary syndrome (ACS) 1 year after the event. We used data from GENESIS-PRAXY, a multicentre prospective study of adults aged 18-55 years, hospitalised for ACS. Participants were 704 adults from 24 centres in Canada, 1 in USA and 1 in Switzerland. Data were collected through questionnaires and chart reviews at baseline and 1 year post-ACS. Fruit and vegetable intake was low among adults with premature ACS, and remained suboptimal at 1 year post-ACS, with only 21% meeting the minimum recommendations of at least 5 daily servings. The findings suggest that patient lifestyle characteristics, such as the number of hours spent at work and baseline intake are factors that may be associated with the intake of fruits and vegetables. More research is needed to assess effective strategies to increase fruit and vegetable intake among patients with premature ACS so that they meet dietary recommendations. PMID:26529090

  10. Acute exercise increases feeding latency in healthy normal weight young males but does not alter energy intake.

    PubMed

    King, James A; Wasse, Lucy K; Stensel, David J

    2013-02-01

    This study investigated the acute influence of exercise on eating behaviour in an ecologically valid setting whereby healthy active males were permitted complete ad libitum access to food. Ten healthy males completed two, 8h trials (exercise and control) in a randomised-crossover design. In the exercise trials participants consumed a breakfast snack and then rested for 1h before undertaking a 60 min run (72% of VO(2)max) on a treadmill. Participants then rested in the laboratory for 6h during which time they were permitted complete ad libitum access to a buffet meal. The timing of meals, energy/macronutrient intake and eating frequency were assessed. Identical procedures were completed in the control trial except no exercise was performed. Exercise increased the length of time (35 min) before participants voluntarily requested to eat afterwards. Despite this, energy intake at the first meal consumed, or at subsequent eating episodes, was not influenced by exercise (total trial energy intake: control 7426 kJ, exercise 7418 kJ). Neither was there any difference in macronutrient intake or meal frequency between trials. These results confirm that food intake remains unaffected by exercise in the immediate hours after but suggest that exercise may invoke a delay before food is desired. PMID:23137828

  11. Chronic intermittent ethanol exposure during adolescence: effects on social behavior and ethanol sensitivity in adulthood

    PubMed Central

    Varlinskaya, Elena I.; Truxell, Eric; Spear, Linda P.

    2014-01-01

    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) 25–45, whereas late adolescent intermittent exposure (l-AIE) was conducted between P45–65. 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 in

  12. Acute effects of ethanol and acetate on glucose kinetics in normal subjects

    SciTech Connect

    Yki-Jaervinen, H.; Koivisto, V.A.; Ylikahri, R.; Taskinen, M.R. )

    1988-02-01

    The authors compared the effects of two ethanol doses on glucose kinetics and assessed the role of acetate as a mediator of ethanol-induced insulin resistance. Ten normal males were studied on four occasions, during which either a low or moderate ethanol, acetate, or saline dose was administered. Both ethanol doses similarly inhibited basal glucose production. The decrease in R{sub a} was matched by a comparable decrease in glucose utilization (R{sub d}), resulting in maintenance of normoglycemia. During hyperinsulinemia glucose disposal was lower in the moderate than the low-dose ethanol or saline studies. During acetate infusion, the blood acetate level was comparable with those in the ethanol studies. Acetate had no effect on glucose kinetics. In conclusion, (1) in overnight fasted subjects, ethanol does not cause hypoglycemia because its inhibitory effect on R{sub a} is counterbalanced by equal inhibition of R{sub d}; (2) basal R{sub a} and R{sub d} are maximally inhibited already by small ethanol doses, whereas inhibition of insulin-stimulated glucose disposal requires a moderate ethanol dose; and (3) acetate is not the mediator of ethanol-induced insulin resistance.

  13. Comparative studies of oral administration of marine collagen peptides from Chum Salmon (Oncorhynchus keta) pre- and post-acute ethanol intoxication in female Sprague-Dawley rats.

    PubMed

    Liang, Jiang; Li, Qiong; Lin, Bing; Yu, Yongchao; Ding, Ye; Dai, Xiaoqian; Li, Yong

    2014-09-01

    The present study aimed to evaluate the effect of an oral administration of marine collagen peptides (MCPs) pre- and post-acute ethanol intoxication in female Sprague-Dawley (SD) rats. MCPs were orally administered to rats at doses of 0 g per kg bw, 2.25 g per kg bw, 4.5 g per kg bw and 9.0 g per kg bw, prior to or after the oral administration of ethanol. Thirty minutes after ethanol treatment, the effect of MCPs on motor incoordination and hypnosis induced by ethanol were investigated using a screen test, fixed speed rotarod test (5 g per kg bw ethanol) and loss of righting reflex (7 g per kg bw ethanol). In addition, the blood ethanol concentrations at 30, 60, 90, and 120 minutes after ethanol administration (5 g per kg bw ethanol) were measured. The results of the screen test and fixed speed rotarod test suggested that treatment with MCPs at 4.5 g per kg bw and 9.0 g per kg bw prior to ethanol could attenuate ethanol-induced loss of motor coordination. Moreover, MCP administered both pre- and post-ethanol treatment had significant potency to alleviate the acute ethanol induced hypnotic states in the loss of righting reflex test. At 30, 60, 90 and 120 minutes after ethanol ingestion at 5 g per kg bw, the blood ethanol concentration (BEC) of control rats significantly increased compared with that in the 4.5 g per kg bw and 9.0 g per kg bw MCP pre-treated groups. However, post-treatment with MCPs did not exert a significant inhibitory effect on the BEC of the post-treated groups until 120 minutes after ethanol administration. Therefore, the anti-inebriation effect of MCPs was verified in SD rats with the possible mechanisms related to inhibiting ethanol absorption and facilitating ethanol metabolism. Moreover, the efficiency was better when MCPs were administered prior to ethanol. PMID:24992080

  14. Self-reported alcohol intake and risk of acute exacerbations of chronic obstructive pulmonary disease: a prospective cohort study

    PubMed Central

    Wetherbee, Erin E; Niewoehner, Dennis E; Sisson, Joseph H; Lindberg, Sarah M; Connett, John E; Kunisaki, Ken M

    2015-01-01

    Objective To evaluate the relationship between alcohol consumption and the risk of acute exacerbation of COPD (AECOPD). Methods and measurements We conducted a secondary analysis of data previously collected in a large, multicenter trial of daily azithromycin in COPD. To analyze the relationship between amount of baseline self-reported alcohol consumption in the past 12 months and subsequent AECOPD, we categorized the subjects as minimal (<1 drink/month), light-to-moderate (1–60 drinks/month), or heavy alcohol users (>60 drinks/month). The primary outcome was time to first AECOPD and the secondary outcome was AECOPD rate during the 1-year study period. Results Of the 1,142 enrolled participants, 1,082 completed baseline alcohol questionnaires and were included in this analysis. Six hundred and forty-five participants reported minimal alcohol intake, 363 reported light-to-moderate intake, and 74 reported heavy intake. There were no statistically significant differences in median time to first AECOPD among minimal (195 days), light-to-moderate (241 days), and heavy drinkers (288 days) (P=0.11). The mean crude rate of AECOPD did not significantly differ between minimal (1.62 events per year) and light-to-moderate (1.44 events per year) (P=0.095), or heavy drinkers (1.68 events per year) (P=0.796). There were no significant differences in hazard ratios for AECOPD after adjustment for multiple covariates. Conclusion Among persons with COPD at high risk of exacerbation, we found no significant relationship between self-reported baseline alcohol intake and subsequent exacerbations. The number of patients reporting heavy alcohol intake was small and further study is needed to determine the effect of heavy alcohol intake on AECOPD risk. PMID:26229455

  15. Developmental differences in EEG and sleep responses to acute ethanol administration and its withdrawal (hangover) in adolescent and adult Wistar rats.

    PubMed

    Ehlers, Cindy L; Desikan, Anita; Wills, Derek N

    2013-12-01

    Age-related differences in sensitivity to the acute effects of alcohol may play an important role in the increased risk for the development of alcoholism seen in teens that begin drinking at an early age. The present study evaluated the acute and protracted (hangover) effects of ethanol in adolescent (P33-P40) and adult (P100-P107) Wistar rats, using the cortical electroencephalogram (EEG). Six minutes of EEG was recorded during waking, 15 min after administration of 0, 1.5, or 3.0 g/kg ethanol, and for 3 h at 20 h post ethanol, during the rats' next sleep cycle. Significantly higher overall frontal and parietal cortical power was seen in a wide range of EEG frequencies in adolescent rats as compared to adult rats in their waking EEG. Acute administration of ethanol did not produce differences between adolescents and adults on behavioral measures of acute intoxication. However, it did produce a significantly less intense acute EEG response to ethanol in the theta frequencies in parietal cortex in the adolescents as compared to the adults. At 20 h following acute ethanol administration, during the rats' next sleep cycle, a decrease in slow-wave frequencies (1-4 Hz) was seen and the adolescent rats were found to display more reduction in the slow-wave frequencies than the adults did. The present study found that adolescent rats, as compared to adults, demonstrate low sensitivity to acute ethanol administration in the theta frequencies and more susceptibility to disruption of slow-wave sleep during hangover. These studies may lend support to the idea that these traits may contribute to increased risk for alcohol use disorders seen in adults who begin drinking in their early teenage years. PMID:24169089

  16. Determination of fatty acid ethyl esters in dried blood spots by LC-MS/MS as markers for ethanol intake: application in a drinking study.

    PubMed

    Luginbühl, Marc; Schröck, Alexandra; König, Stefan; Schürch, Stefan; Weinmann, Wolfgang

    2016-05-01

    The forensic utility of fatty acid ethyl esters (FAEEs) in dried blood spots (DBS) as short-term confirmatory markers for ethanol intake was examined. An LC-MS/MS method for the determination of FAEEs in DBS was developed and validated to investigate FAEE formation and elimination in a drinking study, whereby eight subjects ingested 0.66-0.84 g/kg alcohol to reach blood alcohol concentrations (BAC) of 0.8 g/kg. Blood was taken every 1.5-2 h, BAC was determined, and dried blood spots were prepared, with 50 μL of blood, for the determination of FAEEs. Lower limits of quantitation (LLOQ) were between 15 and 37 ng/mL for the four major FAEEs. Validation data are presented in detail. In the drinking study, ethyl palmitate and ethyl oleate proved to be the two most suitable markers for FAEE determination. Maximum FAEE concentrations were reached in samples taken 2 or 4 h after the start of drinking. The following mean peak concentrations (c̅ max) were reached: ethyl myristate 14 ± 4 ng/mL, ethyl palmitate 144 ± 35 ng/mL, ethyl oleate 125 ± 55 ng/mL, ethyl stearate 71 ± 21 ng/mL, total FAEEs 344 ± 91 ng/mL. Detectability of FAEEs was found to be on the same time scale as BAC. In liquid blood samples containing ethanol, FAEE concentrations increase post-sampling. This study shows that the use of DBS fixation prevents additional FAEE formation in blood samples containing ethanol. Positive FAEE results obtained by DBS analysis can be used as evidence for the presence of ethanol in the original blood sample. Graphical Abstract Time courses for fatty acid ethyl ester (FAEE) concentrations in DBS and ethanol concentrations for subject 1 over a period of 7 h. Ethanol ingestion occured during the first hour of the time course. PMID:26968564

  17. The Zebrafish, a Novel Model Organism for Screening Compounds Affecting Acute and Chronic Ethanol-Induced Effects.

    PubMed

    Tran, S; Facciol, A; Gerlai, R

    2016-01-01

    Alcohol addiction is a major unmet medical and economic issue for which very few efficacious pharmacological treatment options are currently available. The development and identification of new compounds and drugs to treat alcohol addiction is hampered by the high costs and low amenability of traditional laboratory rodents to high-throughput behavioral screens. The zebrafish represents an excellent compromise between systems complexity and practical simplicity by overcoming many limitations inherent in these rodent models. In this chapter, we review current advances in the behavioral and neurochemical characterization of ethanol-induced changes in zebrafish. We also discuss the basic principles and methods of and the most recent advances in using paradigms with which one can screen for compounds altering acute and chronic ethanol-induced effects in zebrafish. PMID:27055623

  18. Excretion of malondialdehyde, formaldehyde, acetaldehyde and acetone in the urine of rats following acute and chronic administration of ethanol.

    PubMed

    Moser, J; Bagchi, D; Akubue, P I; Stohs, S J

    1993-05-01

    Recent studies have shown that xenobiotics which induce oxidative stress result in an increased production and excretion of acetaldehyde (ACT), formaldehyde (FA), acetone (ACON) and malondialdehyde (MDA) in the urine of rats. We have therefore examined the effect of acute and chronic ethanol administration on the excretion of these four lipid metabolites in female Sprague-Dawley rats. Urine samples were collected over dry ice for 6 hr time periods. Aliquots of urine were derivatized with 2,4-dinitrophenylhydrazine HCl, and extracted with n-pentane. High pressure lipid chromatogrpahy (HPLC) was used to quantitate and the hydrazones of the four lipid metabolite products. Following a single, oral, acute dose of 5 g ethanol/kg, urinary excretion of ACT increased approximately 5.8-fold from 6 to 12 hr posttreatment, and decreased thereafter. FA excretion decreased by approximately 50% from 0 to 12 hr, returned to control values in the 18-24 hr urine samples, and was 1.3-fold greater than control values at 42-48 hr. ACON increased 3.1-fold over control values from 0 to 30 hr and remained elevated throughout the remaining 18 hr of the study. The excretion of MDA increased approximately 1.5-fold from 18 to 36 hr, then remained constant through the 48 hr time point. In a separate series of experiments, a chronic oral dose of 0.5 g ethanol/kg was administered to rats for 10 consecutive days and the urinary excretion of the lipid metabolites MDA, FA, ACT and ACON was examined for 11 days, beginning with the first day of ethanol administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8352840

  19. Chlordiazepoxide effects on ethanol self-administration: dependence on concurrent conditions.

    PubMed Central

    Samson, H H; Grant, K A

    1985-01-01

    Experiments examined the effects of acute doses of chlordiazepoxide upon ethanol self-administration in the rat. A concurrent-schedule procedure was used that employed choice between ethanol (5%) and a second fluid (either water or a 1% sucrose solution). When ethanol and water were the available fluids, chlordiazepoxide at doses of 15 and 20 mg/kg reduced ethanol-reinforced responding and intake, with a greater reduction occurring at the 20 mg/kg dose. However, when ethanol and sucrose were concurrently available, in many rats only the 20 mg/kg dose of chlordiazepoxide reduced ethanol-reinforced responding. The differences in dose response function occurred in most animals without large changes in the baseline ethanol-reinforced responding across the two concurrent conditions. Thus the dose-effect curve relating chlordiazepoxide and ethanol self-administration can be altered, dependent upon the nature of the concurrently available reinforcers. PMID:4020323

  20. Energy intake over 2 days is unaffected by acute sprint interval exercise despite increased appetite and energy expenditure.

    PubMed

    Beaulieu, Kristine; Olver, T Dylan; Abbott, Kolten C; Lemon, Peter W R

    2015-01-01

    A cumulative effect of reduced energy intake, increased oxygen consumption, and/or increased lipid oxidation could explain the fat loss associated with sprint interval exercise training (SIT). This study assessed the effects of acute sprint interval exercise (SIE) on energy intake, subjective appetite, appetite-related peptides, oxygen consumption, and respiratory exchange ratio over 2 days. Eight men (25 ± 3 years, 79.6 ± 9.7 kg, body fat 13% ± 6%; mean ± SD) completed 2 experimental treatments: SIE and recovery (SIEx) and nonexercise control. Each 34-h treatment consisted of 2 consecutive 10-h test days. Between 0800-1800 h, participants remained in the laboratory for 8 breath-by-breath gas collections, 3 buffet-type meals, 14 appetite ratings, and 4 blood samples for appetite-related peptides. Treatment comparisons were made using 2-way repeated measures ANOVA or t tests. An immediate, albeit short-lived (<1 h), postexercise suppression of appetite and increase in peptide YY (PYY) were observed (P < 0.001). However, overall hunger and motivation to eat were greater during SIEx (P < 0.02) without affecting energy intake. Total 34-h oxygen consumption was greater during SIEx (P = 0.04), elicited by the 1491-kJ (22%) greater energy expenditure over the first 24 h (P = 0.01). Despite its effects on oxygen consumption, appetite, and PYY, acute SIE did not affect energy intake. Consequently, if these dietary responses to SIE are sustained with regular SIT, augmentations in oxygen consumption and/or a substrate shift toward increased fat use postexercise are most likely responsible for the observed body fat loss with this type of exercise training. PMID:25494974

  1. Short Communication: Is Ethanol-Based Hand Sanitizer Involved in Acute Pancreatitis after Excessive Disinfection?—An Evaluation with the Use of PBPK Model

    PubMed Central

    Huynh-Delerme, Céline; Artigou, Catherine; Bodin, Laurent; Tardif, Robert; Charest-Tardif, Ginette; Verdier, Cécile; Sater, Nessryne; Ould-Elhkim, Mostafa; Desmares, Catherine

    2012-01-01

    An occupational physician reported to the French Health Products Safety Agency (Afssaps) a case of adverse effect of acute pancreatitis (AP) in a teaching nurse, after multiple demonstrations with ethanol-based hand sanitizers (EBHSs) used in a classroom with defective mechanical ventilation. It was suggested by the occupational physician that the exposure to ethanol may have produced a significant blood ethanol concentration and subsequently the AP. In order to verify if the confinement situation due to defective mechanical ventilation could increase the systemic exposure to ethanol via inhalation route, a physiologically based pharmacokinetic (PBPK) modeling was used to predict ethanol blood levels. Under the worst case scenario, the simulation by PBPK modeling showed that the maximum blood ethanol concentration which can be predicted of 5.9 mg/l is of the same order of magnitude to endogenous ethanol concentration (mean = 1.1 mg/L; median = 0.4 mg/L; range = 0–35 mg/L) in nondrinker humans (Al-Awadhi et al., 2004). The present study does not support the likelihood that EBHS leads to an increase in systemic ethanol concentration high enough to provoke an acute pancreatitis. PMID:22577377

  2. Short Communication: Is Ethanol-Based Hand Sanitizer Involved in Acute Pancreatitis after Excessive Disinfection?-An Evaluation with the Use of PBPK Model.

    PubMed

    Huynh-Delerme, Céline; Artigou, Catherine; Bodin, Laurent; Tardif, Robert; Charest-Tardif, Ginette; Verdier, Cécile; Sater, Nessryne; Ould-Elhkim, Mostafa; Desmares, Catherine

    2012-01-01

    An occupational physician reported to the French Health Products Safety Agency (Afssaps) a case of adverse effect of acute pancreatitis (AP) in a teaching nurse, after multiple demonstrations with ethanol-based hand sanitizers (EBHSs) used in a classroom with defective mechanical ventilation. It was suggested by the occupational physician that the exposure to ethanol may have produced a significant blood ethanol concentration and subsequently the AP. In order to verify if the confinement situation due to defective mechanical ventilation could increase the systemic exposure to ethanol via inhalation route, a physiologically based pharmacokinetic (PBPK) modeling was used to predict ethanol blood levels. Under the worst case scenario, the simulation by PBPK modeling showed that the maximum blood ethanol concentration which can be predicted of 5.9 mg/l is of the same order of magnitude to endogenous ethanol concentration (mean = 1.1 mg/L; median = 0.4 mg/L; range = 0-35 mg/L) in nondrinker humans (Al-Awadhi et al., 2004). The present study does not support the likelihood that EBHS leads to an increase in systemic ethanol concentration high enough to provoke an acute pancreatitis. PMID:22577377

  3. Acute effects of oral and intravenous ethanol on rat hepatic enzyme activities.

    PubMed

    Stifel, F B; Greene, H L; Lufkin, E G; Wrensch, M R; Hagler, L; Herman, R H

    1976-05-28

    1. Oral administration of ethanol (3 ml) of 95% in 12 ml total volume over a two day period) significantly decrease plasma glucose and insulin levels and the activities of two key gluconeogenic enzymes, pyruvate carboxylase (pyruvate: CO2 ligase (ADP), EC 6.4.1.1) and fructose diphosphatase, (D-Fru-1,6-P2 1-phosphohydrolase, EC 3.1.3.11), and one glycolytic enzyme, fructose-1,6-P2 aldolase (Fru-1,6-P2 D-glyceraldehyde-3-P lyase, EC 4.1.2.13). In each instance, the administration of 2400 mug daily of oral folate in conjuction with the ethanol prevented these alterations in carbohydrate metabolism. 2. Intravenous injection of ethanol produced a rapid decrease (within 10--15 min) in the activities of hepatic phosphofructokinase, (ATP:D-fructose-6-phosphate 6-phosphotransferase, EC 2.7.1.11), pyruvate kinase, (ATP:pyruvate phosphotransferase, EC 2.7.1.40), fructose diphosphatase and fructose-1,6-P2 aldolase. 3. Intravenous ethanol significantly increased hepatic cyclic AMP concentration approximately 60% within 10 min, while oral ethanol did not alter hepatic cyclic AMP concentrations. 4. These data confirm the known antagonism ethanol and folate and suggest that oral folate might offer a protective effect against hypoglycemia in rats receiving ethanol. PMID:179581

  4. [On the importance of a comprehensive study for diagnostics of death from acute ethanol poisoning and coronary heart disease].

    PubMed

    Porodenko, V A; Korkhmazov, V T

    2011-01-01

    Over 30 000 cases of acute poisoning with ethyl alcohol and its surrogates are recorded annually in this country. Differential diagnostics between fatal poisoning and death from coronary heart disease encounters serious difficulties. The authors report a comprehensive forensic chemical, morphometric, and pathomorphological study of the activity of ethanol-oxidizing enzyme systems in the internal organs. The results of histochemical examination provide a basis for the extension of diagnostic potential of the available methods and the enhancement of the objective value of expert reports. PMID:21866846

  5. Sex differences in sensitivity to the social consequences of acute ethanol and social drinking during adolescence

    PubMed Central

    Varlinskaya, Elena I.; Truxell, Eric M.; Spear, Linda P.

    2015-01-01

    In human adolescents, sociable males frequently drink to enhance positive emotional states, whereas anxious females often drink to avoid negative affective states. This study used a rat model of adolescence to provide information regarding possible sex differences in contributors to social drinking. The effects of ethanol (0, 0.5, and 0.75 g/kg) on play fighting and social preference were assessed on P30, P32, and P34 using a within-subject design. Then animals were tested in a social drinking paradigm (P37-P40), with this testing revealing high drinkers and low drinkers. Sex differences in sensitivity to ethanol emerged among high and low drinkers. High socially drinking males, but not females, when tested prior to drinking sessions, showed significant increases in play fighting at both doses. In low drinking males, play fighting was increased by 0.5 g/kg ethanol, whereas the higher dose of 0.75 g/kg produced significant decreases in play fighting. High drinking females initially showed low levels of social preference than high drinking males and low drinking females and were extremely sensitive to ethanol-induced enhancement of this social measure. Low social drinkers, both males and females, were more sensitive to the suppressing effects of ethanol on social preference following 0.75 g/kg ethanol. These findings indicate that during adolescence enhanced sensitivity to the facilitating effects of ethanol on play fighting is associated with heavy drinking among males, whereas low social preference together with high sensitivity to ethanol-induced enhancement of social preference is related to high social drinking in females. PMID:25557799

  6. Sex differences in sensitivity to the social consequences of acute ethanol and social drinking during adolescence.

    PubMed

    Varlinskaya, Elena I; Truxell, Eric M; Spear, Linda P

    2015-04-01

    In human adolescents, sociable males frequently drink to enhance positive emotional states, whereas anxious females often drink to avoid negative affective states. This study used a rat model of adolescence to provide information regarding possible sex differences in contributors to social drinking. The effects of ethanol (0, 0.5, and 0.75g/kg) on play fighting and social preference were assessed on P30, P32, and P34 using a within-subject design. Then animals were tested in a social drinking paradigm (P37-P40), with this testing revealing high drinkers and low drinkers. Sex differences in sensitivity to ethanol emerged among high and low drinkers. High socially drinking males, but not females, when tested prior to drinking sessions, showed significant increases in play fighting at both doses. In low drinking males, play fighting was increased by 0.5g/kg ethanol, whereas the higher dose of 0.75g/kg produced significant decreases in play fighting. High drinking females initially showed low levels of social preference than high drinking males and low drinking females and were extremely sensitive to ethanol-induced enhancement of this social measure. Low social drinkers, both males and females, were more sensitive to the suppressing effects of ethanol on social preference following 0.75g/kg ethanol. These findings indicate that during adolescence enhanced sensitivity to the facilitating effects of ethanol on play fighting is associated with heavy drinking among males, whereas low social preference together with high sensitivity to ethanol-induced enhancement of social preference is related to high social drinking in females. PMID:25557799

  7. Emotional reactivity to incentive downshift as a correlated response to selection of high and low alcohol preferring mice and an influencing factor on ethanol intake.

    PubMed

    Matson, Liana M; Grahame, Nicholas J

    2015-11-01

    Losing a job or significant other are examples of incentive loss that result in negative emotional reactions. The occurrence of negative life events is associated with increased drinking (Keyes, Hatzenbuehler, & Hasin, 2011). Further, certain genotypes are more likely to drink alcohol in response to stressful negative life events (Blomeyer et al., 2008; Covault et al., 2007). Shared genetic factors may contribute to alcohol drinking and emotional reactivity, but this relationship is not currently well understood. We used an incentive downshift paradigm to address whether emotional reactivity is elevated in mice predisposed to drink alcohol. We also investigated if ethanol drinking is influenced in High Alcohol Preferring mice that had been exposed to an incentive downshift. Incentive downshift procedures have been widely utilized to model emotional reactivity, and involve shifting a high reward group to a low reward and comparing the shifted group to a consistently rewarded control group. Here, we show that replicate lines of selectively bred High Alcohol Preferring mice exhibited larger successive negative contrast effects than their corresponding replicate Low Alcohol Preferring lines, providing strong evidence for a genetic association between alcohol drinking and susceptibility to the emotional effects of negative contrast. These mice can be used to study the shared neurological and genetic underpinnings of emotional reactivity and alcohol preference. Unexpectedly, an incentive downshift suppressed ethanol drinking immediately following an incentive downshift. This could be due to a specific effect of negative contrast on ethanol consumption or a suppressive effect on consummatory behavior in general. These data suggest that either alcohol intake does not provide the anticipated negative reinforcement, or that a single test was insufficient for animals to learn to drink following incentive downshift. However, the emotional intensity following incentive

  8. The effects of acute exposure to ethanol on neurotensin and guanine nucleotide-stimulation of phospholipase C activity in intact NIE-115 neuroblastoma cells

    SciTech Connect

    Smith, T.L. )

    1990-01-01

    Both ethanol and neurotensin produce sedation and hypothermia. When administered in combination the behavioral effects of these two substances are potentiated. In order to better understand the biochemical nature of this interaction, the direct effects of ethanol on neurotensin receptors and an associated signal transduction process were determined in NIE-115 neuroblastoma cells. Ethanol in physiologically relevant concentrations significantly reduced neurotensin stimulated ({sup 3}H)inositol phosphate production while having no effect on the specific binding of ({sup 3}H)neurotensin. In addition, ethanol up to 200 mM had no effect on GTPYS mediated ({sup 3}H)inositol phosphate production. The results indicate that acute exposure ethanol partially disrupts the normal coupling of activated neurotensin receptors to the guanine nucleotide binding protein associated with phospholipase C.

  9. The effect of chronic and acute ethanol treatment on morphology, lipid peroxidation, enzyme activities and Na+ transport systems on WRL-68 cells.

    PubMed

    Gutiérrez-Ruiz, M C; Bucio, L; Souza, V; Cárabez, A

    1995-04-01

    In this study we measured some parameters that are associated with ethanol damage to the liver. The method allowed us to determine the injury that chronic and acute ethanol treatments produce at the cellular level without interference from homeostatic or compensatory mechanisms. The system used is a hepatic fetal human cell line, WRL-68, which retains, in culture, many of the liver-specific functions. WRL-68 cells do not metabolise ethanol, and consequently we could evaluate the effect of ethanol alone. We explored two different conditions: 30 days with 0.1 M ethanol (chronic treatment) and 24 h in the presence of 0.5 M ethanol (acute treatment). 1. The transmission electron microscopy studies revealed, in both treatments, the presence of granules not usually present in the cytoplasm of control cells and morphological mitochondrial alterations in chronically treated cells. 2. Lipid peroxidation, measured as the rate of malondialdehyde production, increased three and a half times in acutely treated cells and about twofold in chronically treated cells. 3. The percentage of total activity (activity in the medium/(activity in the medium + activity of the cells). 100) and the enzymatic activity in the culture medium of gamma glutamyl transpeptidase (GGT), alanine amino transferase (ALAT), aspartate amino transferase (ASAT) and alkaline phosphatase (AI-P), increased. 4. We measured some parameters related to the transport of sodium across the membrane. Cells chronically treated with ethanol had higher rate constants and effluxes than control cells. There was no difference between the total and passive efflux. Ethanol treated cells apparently lacked the ouabain sensitive pathway. In acutely treated cells, the total sodium efflux and the rate constant were enhanced. Sodium pools in the acutely treated cells were diminished and active sodium pumping was seven times higher than in control cells. 5. We determined the number of high affinity ouabain binding sites per cell

  10. Adolescent and adult rats differ in the amnesic effects of acute ethanol in two hippocampus-dependent tasks: Trace and contextual fear conditioning.

    PubMed

    Hunt, Pamela S; Barnet, Robert C

    2016-02-01

    Experience-produced deficits in trace conditioning and context conditioning have been useful tools for examining the role of the hippocampus in learning. It has also been suggested that learning in these tasks is especially vulnerable to neurotoxic effects of alcohol during key developmental periods such as adolescence. In five experiments we systematically examined the presence and source of age-dependent vulnerability to the memory-disrupting effects of acute ethanol in trace conditioning and contextual fear conditioning. In Experiment 1a pre-training ethanol disrupted trace conditioning more strongly in adolescent (postnatal day, PD30-35) than adult rats (PD65-75). In Experiment 1b when pre-training ethanol was accompanied by pre-test ethanol no deficit in trace conditioning was observed in adolescents, suggesting that state-dependent retrieval failure mediated ethanol's disruption of trace conditioning at this age. Experiment 2a and b examined the effect of ethanol pretreatment on context conditioning. Here, adult but not adolescent rats were impaired in conditioned freezing to context cues. Experiment 2c explored state-dependency of this effect. Pre-training ethanol continued to disrupt context conditioning in adults even when ethanol was also administered prior to test. Collectively these findings reveal clear age-dependent and task-dependent vulnerabilities in ethanol's disruptive effects on hippocampus-dependent memory. Adolescents were more disrupted by ethanol in trace conditioning than adults, and adults were more disrupted by ethanol in context conditioning than adolescents. We suggest that adolescents may be more susceptible to changes in internal state (state-dependent retrieval failure) than adults and that ethanol disrupted performance in trace and context conditioning through different mechanisms. Relevance of these findings to theories of hippocampus function is discussed. PMID:26192910

  11. Acute effects of a single exercise class on appetite, energy intake and mood. Is there a time of day effect?

    PubMed

    Maraki, M; Tsofliou, F; Pitsiladis, Y P; Malkova, D; Mutrie, N; Higgins, S

    2005-12-01

    This study aimed to investigate the acute effects of a single exercise class on appetite sensations, energy intake and mood, and to determine if there was a time of day effect. Twelve healthy, young, normal weight females, who were non-regular exercisers, participated in four trials: morning control, morning exercise, evening control and evening exercise. Exercise trials were a one-hour class of aerobic and muscle conditioning exercise of varying intensities, to music. Control trials were a one-hour rest. Ratings of perceived exertion were significantly greater during the warm-up and muscle conditioning parts of the morning exercise trial compared to those of the evening exercise trial. Although both exercise trials, compared to control trials, produced an increase in appetite sensations, they did not alter energy intake and produced a decrease in 'relative' energy intake. In relation to mood, both exercise trials increased positive affect and decreased negative affect. These results suggest that a single exercise class, representative of that offered by many sports centres, regardless of whether it is performed in the morning or evening produces a short-term negative energy balance and improves mood in normal weight women. However, when this type of exercise was performed in the morning it was perceived to require more effort. PMID:16157416

  12. The Acute-Phase Protein Orosomucoid Regulates Food Intake and Energy Homeostasis via Leptin Receptor Signaling Pathway.

    PubMed

    Sun, Yang; Yang, Yili; Qin, Zhen; Cai, Jinya; Guo, Xiuming; Tang, Yun; Wan, Jingjing; Su, Ding-Feng; Liu, Xia

    2016-06-01

    The acute-phase protein orosomucoid (ORM) exhibits a variety of activities in vitro and in vivo, notably modulation of immunity and transportation of drugs. We found in this study that mice lacking ORM1 displayed aberrant energy homeostasis characterized by increased body weight and fat mass. Further investigation found that ORM, predominantly ORM1, is significantly elevated in sera, liver, and adipose tissues from the mice with high-fat diet (HFD)-induced obesity and db/db mice that develop obesity spontaneously due to mutation in the leptin receptor (LepR). Intravenous or intraperitoneal administration of exogenous ORM decreased food intake in C57BL/6, HFD, and leptin-deficient ob/ob mice, which was absent in db/db mice and was significantly reduced in mice with arcuate nucleus (ARC) LepR knockdown, whereas enforced expression of ORM1 in ARC significantly decreased food intake, body weight, and serum insulin level. Furthermore, we found that ORM is able to bind directly to LepR and activate the receptor-mediated JAK2-STAT3 signaling in hypothalamus tissue and GT1-7 cells, which was derived from hypothalamic tumor. These data indicated that ORM could function through LepR to regulate food intake and energy homeostasis in response to nutrition status. Modulating the expression of ORM is a novel strategy for the management of obesity and related metabolic disorders. PMID:27207522

  13. Intra-nucleus accumbens shell injections of R(+)- and S(-)-baclofen bidirectionally alter binge-like ethanol, but not saccharin, intake in C57Bl/6J mice

    PubMed Central

    Kasten, Chelsea R.; Boehm, Stephen L.

    2014-01-01

    The GABAB agonist baclofen has been widely researched clinically and preclinically as a treatment of alcohol use disorders (AUDs). However, the efficacy of baclofen remains uncertain. The clinically used racemic compound can be separated into separate enantiomers. These enantiomers have produced different profiles in behavioral assays, with the S- compound often being ineffective compared to the R- compound, or the S- compound antagonizing the effects of the R- compound. We have previously demonstrated that the R(+)-baclofen enantiomer decreases binge-like ethanol intake in the Drinking-in-the-Dark (DID) paradigm, whereas the S(-)-baclofen enantiomer increases ethanol intake. One area implicated in drug abuse is the nucleus accumbens shell (NACsh).The current study sought to define the role of the NACsh in the enantioselective effects of baclofen on binge-like ethanol consumption by directly microinjecting each enantiomer into the structure. Following bilateral cannulation of the NACsh, C57Bl/6J mice were given 5 days of access to ethanol or saccharin for 2 hours, 3 hours into the dark cycle. On Day 5 mice were given an injection of aCSF, 0.02 R(+)-, 0.04R(+)-, 0.08 S(-)-, or 0.16 S(-)-baclofen (μg/side dissolved in 200nl of aCSF). It was found that the R(+)-baclofen dose-dependently decreased ethanol consumption, whereas the high S(-)-baclofen dose increased ethanol consumption, compared to the aCSF group. Saccharin consumption was not affected. These results further confirm that GABAB receptors and the NACsh shell are integral in mediating ethanol intake. They also demonstrate that baclofen displays bidirectional, enantioselective effects which are important when considering therapeutic uses of the drug. PMID:25026094

  14. Acute Heat Stress and Reduced Nutrient Intake Alter Intestinal Proteomic Profile and Gene Expression in Pigs

    PubMed Central

    Pearce, Sarah C.; Lonergan, Steven M.; Huff-Lonergan, Elisabeth; Baumgard, Lance H.; Gabler, Nicholas K.

    2015-01-01

    Heat stress and reduced feed intake negatively affect intestinal integrity and barrier function. Our objective was to compare ileum protein profiles of pigs subjected to 12 hours of HS, thermal neutral ad libitum feed intake, or pair-fed to heat stress feed intake under thermal neutral conditions (pair-fed thermal neutral). 2D-Differential In Gel Electrophoresis and gene expression were performed. Relative abundance of 281 and 138 spots differed due to heat stress, compared to thermal neutral and pair-fed thermal neutral pigs, respectively. However, only 20 proteins were different due to feed intake (thermal neutral versus pair-fed thermal neutral). Heat stress increased mRNA expression of heat shock proteins and protein abundance of heat shock proteins 27, 70, 90-α and β were also increased. Heat stress reduced ileum abundance of several metabolic enzymes, many of which are involved in the glycolytic or TCA pathways, indicating a change in metabolic priorities. Stress response enzymes peroxiredoxin-1 and peptidyl-prolyl cis-trans isomerase A were decreased in pair-fed thermal neutral and thermal neutral pigs compared to heat stress. Heat stress increased mRNA abundance markers of ileum hypoxia. Altogether, these data show that heat stress directly alters intestinal protein and mRNA profiles largely independent of reduced feed intake. These changes may be related to the reduced intestinal integrity associated with heat stress. PMID:26575181

  15. Gynura procumbens Reverses Acute and Chronic Ethanol-Induced Liver Steatosis through MAPK/SREBP-1c-Dependent and -Independent Pathways.

    PubMed

    Li, Xiao-Jun; Mu, Yun-Mei; Li, Ting-Ting; Yang, Yan-Ling; Zhang, Mei-Tuo; Li, Yu-Sang; Zhang, Wei Kevin; Tang, He-Bin; Shang, Hong-Cai

    2015-09-30

    The present study aimed to evaluate the hepatoprotective effect and mechanism of action of Gynura procumbens on acute and chronic ethanol-induced liver injuries. Ethanol extract from G. procumbens stems (EEGS) attenuated acute ethanol-induced serum alanine aminotransferase levels and hepatic lipid accumulation. Therefore, EEGS was successively extracted by petroleum, ethyl acetate, and n-butyl alcohol. The results showed that the n-butyl alcohol extract was the active fraction of EEGS, and hence it was further fractionated on a polyamide glass column. The 60% ethanol-eluted fraction that contained 13.6% chlorogenic acid was the most active fraction, and its effect was further evaluated using a chronic model. Both the n-butyl alcohol extract and the 60% ethanol-eluted fraction inhibited chronic ethanol-induced hepatic lipid accumulation by modulating lipid metabolism-related regulators through MAPK/SREBP-1c-dependent and -independent signaling pathways and ameliorated liver steatosis. Our findings suggest that EEGS and one of its active ingredients, chlorogenic acid, may be developed as potential effective agents for ethanol-induced liver injury. PMID:26345299

  16. Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women

    PubMed Central

    Coggan, Andrew R.; Leibowitz, Joshua L.; Kadkhodayan, Ana; Thomas, Deepak T.; Ramamurthy, Sujata; Spearie, Catherine Anderson; Waller, Suzannea; Farmer, Marsha; Peterson, Linda R.

    2014-01-01

    Nitric oxide (NO) has been demonstrated to enhance the maximal shortening velocity and maximal power of rodent muscle. Dietary nitrate (NO3-) intake has been demonstrated to increase NO bioavailability in humans. We therefore hypothesized that acute dietary NO3- intake (in the form of a concentrated beetroot juice (BRJ) supplement) would improve muscle speed and power in humans. To test this hypothesis, healthy men and women (n=12; age=22-50 y) were studied using a randomized, double-blind, placebo-controlled crossover design. After an overnight fast, subjects ingested 140 mL of BRJ either containing or devoid of 11.2 mmol of NO3-. After 2 h, knee extensor contractile function was assessed using a Biodex 4 isokinetic dynamometer. Breath NO levels were also measured periodically using a Niox Mino analyzer as a biomarker of whole-body NO production. No significant changes in breath NO were observed in the placebo trial, whereas breath NO rose by 61% (P<0.001; effect size=1.19) after dietary NO3- intake. This was accompanied by a 4% (P<0.01; effect size=0.74) increase in peak knee extensor power at the highest angular velocity tested (i.e., 6.28 rad/s). Calculated maximal knee extensor power was therefore greater (i.e., 7.90±0.59 vs. 7.44±0.53 W/kg; P<0.05; effect size=0.63) after dietary NO3- intake, as was the calculated maximal velocity (i.e., 14.5±0.9 vs. 13.1±0.8 rad/s; P<0.05; effect size=0.67). No differences in muscle function were observed during 50 consecutive knee extensions performed at 3.14 rad/s. We conclude that acute dietary NO3- intake increases whole-body NO production and muscle speed and power in healthy men and women. PMID:25199856

  17. Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women.

    PubMed

    Coggan, Andrew R; Leibowitz, Joshua L; Kadkhodayan, Ana; Thomas, Deepak P; Ramamurthy, Sujata; Spearie, Catherine Anderson; Waller, Suzanne; Farmer, Marsha; Peterson, Linda R

    2015-08-01

    Nitric oxide (NO) has been demonstrated to enhance the maximal shortening velocity and maximal power of rodent muscle. Dietary nitrate (NO3(-)) intake has been demonstrated to increase NO bioavailability in humans. We therefore hypothesized that acute dietary NO3(-) intake (in the form of a concentrated beetroot juice (BRJ) supplement) would improve muscle speed and power in humans. To test this hypothesis, healthy men and women (n = 12; age = 22-50 y) were studied using a randomized, double-blind, placebo-controlled crossover design. After an overnight fast, subjects ingested 140 mL of BRJ either containing or devoid of 11.2 mmol of NO3(-). After 2 h, knee extensor contractile function was assessed using a Biodex 4 isokinetic dynamometer. Breath NO levels were also measured periodically using a Niox Mino analyzer as a biomarker of whole-body NO production. No significant changes in breath NO were observed in the placebo trial, whereas breath NO rose by 61% (P < 0.001; effect size = 1.19) after dietary NO3(-) intake. This was accompanied by a 4% (P < 0.01; effect size = 0.74) increase in peak knee extensor power at the highest angular velocity tested (i.e., 6.28 rad/s). Calculated maximal knee extensor power was therefore greater (i.e., 7.90 ± 0.59 vs. 7.44 ± 0.53 W/kg; P < 0.05; effect size = 0.63) after dietary NO3(-) intake, as was the calculated maximal velocity (i.e., 14.5 ± 0.9 vs. 13.1 ± 0.8 rad/s; P < 0.05; effect size = 0.67). No differences in muscle function were observed during 50 consecutive knee extensions performed at 3.14 rad/s. We conclude that acute dietary NO3(-) intake increases whole-body NO production and muscle speed and power in healthy men and women. PMID:25199856

  18. Effects of Acute Prenatal Exposure to Ethanol on microRNA Expression are Ameliorated by Social Enrichment.

    PubMed

    Ignacio, Cherry; Mooney, Sandra M; Middleton, Frank A

    2014-01-01

    Fetal alcohol spectrum disorders (FASDs) are associated with abnormal social behavior. These behavioral changes may resemble those seen in autism. Rats acutely exposed to ethanol on gestational day 12 show decreased social motivation at postnatal day 42. We previously showed that housing these ethanol-exposed rats with non-exposed controls normalized this deficit. The amygdala is critical for social behavior and regulates it, in part, through connections with the basal ganglia, particularly the ventral striatum. MicroRNAs (miRNAs) are short, hairpin-derived RNAs that repress mRNA expression. Many brain disorders, including FASD, show dysregulation of miRNAs. In this study, we tested if miRNA and mRNA networks are altered in the amygdala and ventral striatum as a consequence of prenatal ethanol exposure and show any evidence of reversal as a result of social enrichment. RNA samples from two different brain regions in 72 male and female adolescent rats were analyzed by RNA-Seq and microarray analysis. Several miRNAs showed significant changes due to prenatal ethanol exposure and/or social enrichment in one or both brain regions. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. Several miRNA changes caused by ethanol were reversed by social enrichment, including mir-204, mir-299a, miR-384-5p, miR-222-3p, miR-301b-3p, and mir-6239. Moreover, enriched gene networks incorporating the targets of these miRNAs also showed reversal. We also extended our previously published mRNA expression analysis by directly examining all annotated brain-related canonical pathways. The additional pathways that were most strongly affected at the mRNA level included p53, CREB, glutamate, and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for social enrichment to reverse the effects of ethanol exposure through widespread influences on gene expression. PMID:25309888

  19. Pyranocycloartobiloxanthone A, a novel gastroprotective compound from Artocarpus obtusus Jarret, against ethanol-induced acute gastric ulcer in vivo.

    PubMed

    Sidahmed, Heyam M A; Hashim, Najihah Mohd; Amir, Junaidah; Abdulla, Mahmood Ameen; Hadi, A Hamid A; Abdelwahab, Siddig Ibrahim; Taha, Manal Mohamed Elhassan; Hassandarvish, Pouya; Teh, Xinsheng; Loke, Mun Fai; Vadivelu, Jamuna; Rahmani, Mawardi; Mohan, Syam

    2013-07-15

    Pyranocycloartobiloxanthone A (PA), a xanthone derived from the Artocarpus obtusus Jarret, belongs to the Moraceae family which is native to the tropical forest of Malaysia. In this study, the efficacy of PA as a gastroprotective compound was examined against ethanol-induced ulcer model in rats. The rats were pretreated with PA and subsequently exposed to acute gastric lesions induced by absolute ethanol. The ulcer index, gastric juice acidity, mucus content, histological analysis, glutathione (GSH) levels, malondialdehyde level (MDA), nitric oxide (NO) and non-protein sulfhydryl group (NP-SH) contents were evaluated in vivo. The activities of PA as anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitor and free radical scavenger were also investigated in vitro. The results showed that the oral administration of PA protects gastric mucosa from ethanol-induced gastric lesions. PA pretreatment significantly (p<0.05) restored the depleted GSH, NP-SH and NO levels in the gastric homogenate. Moreover, PA significantly (p<0.05) reduced the elevated MDA level due to ethanol administration. The gastroprotective effect of PA was associated with an over expression of HSP70 and suppression of Bax proteins in the ulcerated tissue. In addition, PA exhibited a potent FRAP value and significant COX-2 inhibition. It also showed a significant minimum inhibitory concentration (MIC) against H. pylori bacterium. The efficacy of PA was accomplished safely without the presence of any toxicological parameters. The results of the present study indicate that the gastroprotective effect of PA might contribute to the antioxidant and anti-inflammatory properties as well as the anti-apoptotic mechanism and antibacterial action against Helicobacter pylori. PMID:23570997

  20. Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats

    PubMed Central

    Birdane, Fatih Mehmet; Cemek, Mustafa; Birdane, Yavuz Osman; Gülçin, İlhami; Büyükokuroğlu, Mehmet Emin

    2007-01-01

    AIM: To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vulgare (FVE) on ethanol-induced gastric lesions in rats. METHODS: FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated; whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid, retinol and β-carotene levels were measured in all the groups. RESULTS: It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 ± 2.81 vs 13.15 ± 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid, retinol and β-carotene levels. CONCLUSION: FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity. PMID:17278229

  1. Acute ethanol administration affects zebrafish preference for a biologically inspired robot.

    PubMed

    Spinello, Chiara; Macrì, Simone; Porfiri, Maurizio

    2013-08-01

    Preclinical animal models constitute a cornerstone against which the reward processes involved in drug addiction are often studied and dissected. While rodents have traditionally represented the species of choice, a growing body of literature indicates that zebrafish are emerging as a valuable model organism. Specifically, several studies demonstrate that the effects of ethanol at the level of emotional- and cognitive-related domains can be reliably investigated using zebrafish. The rapidly evolving nature of these efforts allows substantial room for the development of novel experimental paradigms suited to this freshwater species. The field of ethorobotics may prove particularly beneficial, due to its ability to convey fully controllable and easily reproducible experimental tools. In this study, we addressed the possibility of using a biologically inspired robot to investigate the emotionally related properties of ethanol in a preference task in zebrafish. To this aim, we evaluated wild-type zebrafish preference toward a robotic stimulus and addressed whether ethanol administration (0.25% and 1.00% ethanol/water concentration) may alter such preferences. In accordance with our previous studies, we observed that zebrafish exhibit a natural attraction toward the robot. Additionally, in agreement with our predictions, we showed that ethanol administration abolishes such preferences. This work is the first to demonstrate that robotic stimuli can be used in zebrafish to investigate the reward-related properties of alcohol. PMID:23725654

  2. Effects of acute ethanol administration and chronic stress exposure on social investigation and 50kHz ultrasonic vocalizations in adolescent and adult male Sprague-Dawley rats.

    PubMed

    Willey, Amanda R; Spear, Linda P

    2013-04-01

    Adolescents drink largely in social situations, likely in an attempt to facilitate social interactions. This study sought to examine alterations in the incentive salience of a social stimulus following repeated stress exposure and acute ethanol administration in adolescent and adult male Sprague-Dawley rats. Subjects were either exposed to 5days of restraint stress, chronic variable stress (CVS), which consisted of a different stressor every day, or non-stressed. On test day, the animals were injected with 0, 0.25, 0.5, or 0.75g/kg ethanol and placed in a social approach test in which they could see, hear, and smell a social conspecific, but could not physically interact with it. All the animals showed an interest in the social stimulus, with adolescents engaging in more social investigation than adults. Restraint stressed adults showed ethanol-induced increases in social investigation, while ethanol effects were not seen in any other group. An ethanol-associated increase in 50kHz ultrasonic vocalization (USV) production was only evident in restraint stressed adolescents following 0.75g/kg ethanol. 50kHz USVs were not correlated with time spent investigating the social stimulus in any test condition. These results show that age differences in the facilitatory effects of ethanol on incentive salience of social stimuli are moderated by stress, with the facilitation of social approach by ethanol only evident in restraint stressed adults. PMID:23360955

  3. Effects of ceftriaxone on ethanol, nicotine or sucrose intake by alcohol-preferring (P) rats and its association with GLT-1 expression.

    PubMed

    Sari, Youssef; Toalston, Jamie E; Rao, P S S; Bell, Richard L

    2016-06-21

    Increased glutamatergic neurotransmission appears to mediate the reinforcing properties of drugs of abuse, including ethanol (EtOH). We have shown that administration of ceftriaxone (CEF), a β-lactam antibiotic, reduced EtOH intake and increased glutamate transporter 1 (GLT-1) expression in mesocorticolimbic regions of male and female alcohol-preferring (P) rats. In the present study, we tested whether CEF administration would reduce nicotine (NIC) and/or EtOH intake by adult female P rats. P rats were randomly assigned to 4 groups: (a) 5% sucrose (SUC) or 10% SUC [SUC], (b) 5% SUC+0.07mg/ml NIC and 10% SUC+0.14mg/ml NIC [NIC-SUC], 15% EtOH and 30% EtOH [EtOH] and (d) 15% EtOH+0.07mg/ml NIC and 30% EtOH+0.14mg/ml NIC [NIC-EtOH]. After achieving stable intakes (4weeks), the rats were administered 7 consecutive, daily i.p. injections of either saline or 200mg/kg CEF. The effects of CEF on intake were significant but differed across the reinforcers; such that ml/kg/day SUC was reduced by ∼30%, mg/kg/day NIC was reduced by ∼70% in the NIC-SUC group and ∼40% in the EtOH-NIC group, whereas g/kg/day EtOH was reduced by ∼40% in both the EtOH and EtOH-NIC group. The effects of CEF on GLT-1 expression were also studied. We found that CEF significantly increased GLT-1 expression in the prefrontal cortex and the nucleus accumbens of the NIC and NIC-EtOH rats as compared to NIC and NIC-EtOH saline-treated rats. These findings provide further support for GLT-1-associated mechanisms in EtOH and/or NIC abuse. The present results along with previous reports of CEF's efficacy in reducing cocaine self-administration in rats suggest that modulation of GLT-1 expression and/or activity is an important pharmacological target for treating polysubstance abuse and dependence. PMID:27060486

  4. Acute prenatal exposure to ethanol on gestational day 12 elicits opposing deficits in social behaviors and anxiety-like behaviors in Sprague Dawley rats.

    PubMed

    Diaz, Marvin R; Mooney, Sandra M; Varlinskaya, Elena I

    2016-09-01

    Our previous research has shown that in Long Evans rats acute prenatal exposure to a high dose of ethanol on gestational day (G) 12 produces social deficits in male offspring and elicits substantial decreases in social preference relative to controls, in late adolescents and adults regardless of sex. In order to generalize the observed detrimental effects of ethanol exposure on G12, pregnant female Sprague Dawley rats were exposed to ethanol or saline and their offspring were assessed in a modified social interaction (SI) test as early adolescents, late adolescents, or young adults. Anxiety-like behavior was also assessed in adults using the elevated plus maze (EPM) or the light/dark box (LDB) test. Age- and sex-dependent social alterations were evident in ethanol-exposed animals. Ethanol-exposed males showed deficits in social investigation at all ages and age-dependent alterations in social preference. Play fighting was not affected in males. In contrast, ethanol-exposed early adolescent females showed no changes in social interactions, whereas older females demonstrated social deficits and social indifference. In adulthood, anxiety-like behavior was decreased in males and females prenatally exposed to ethanol in the EPM, but not the LDB. These findings suggest that social alterations associated with acute exposure to ethanol on G12 are not strain-specific, although they are more pronounced in Long Evans males and Sprague Dawley females. Furthermore, given that anxiety-like behaviors were attenuated in a test-specific manner, this study indicates that early ethanol exposure can have differential effects on different forms of anxiety. PMID:27154534

  5. Interactions of ethanol on the acute toxicity of cocaine in the rat

    SciTech Connect

    Trouve, R. ); Latour, C ); Nahas, G.G. Columbia Univ., New York, NY )

    1992-02-26

    Administration of 65 mg/kg in the awake rate, restrained and instrumented, is associated with cardiovascular toxicity, convulsions and lethality within 9 feet 44 inches {plus minus} 4 feet 56 inches. Such an outcome is prevented if selected Ca{sup 2+} antagonists are administered intraarterially 5 minutes following cocaine. Four additional groups of Sprague Dawley rats were studied. The first was administered I.P. ethanol 1.5-2.0 gr. Such doses were well tolerated only producing hypertension of 50 minutes duration and all animals survived without apparent ill effects. Second and third groups were first administered the same doses of ethanol and 15 minutes later 65 mg/kg of cocaine. Survival time was 5 feet 49 inches with 1.5 mg/kg ethanol and 5 feet 57 inches {plus minus} 1 foot 26 inches with 2 mg/kg, significantly less than after cocaine administration alone. In a fourth group, animals were treated intraarterially with nicardipine or flunarizine, 2 minutes after cocaine. Survival time was not different from saline control. Ethanol enhances significantly cocaine lethal toxicity in the rate and prevents the protective effects of antidotes to this alkaloid.

  6. CHOLINE AMELIORATES DEFICITS IN BALANCE CAUSED BY ACUTE NEONATAL ETHANOL EXPOSURE

    PubMed Central

    Bearer, Cynthia F.; Wellmann, Kristen A.; Tang, Ningfeng; He, Min; Mooney, Sandra M.

    2015-01-01

    Fetal alcohol spectrum disorder (FASD) is estimated to occur in 1% of all live births. The developing cerebellum is vulnerable to the toxic effects of alcohol. People with FASD have cerebellar hypoplasia and developmental deficits associated with cerebellar injury. Choline is an essential nutrient but many diets in the USA are choline deficient. In rats, choline given with or following alcohol exposure reduces many alcohol-induced neurobehavioral deficits, but not those associated with cerebellar function. Our objective was to determine if choline supplementation prior to alcohol exposure would ameliorate the impact of ethanol on a cerebellar-associated behavioral test in mice. Pregnant C57Bl6/J mice were maintained on a choline deficient diet from embryonic day 4.5. On postnatal day 1 (P1), pups were assigned to one of 8 treatment groups: choline (C) or saline (S) pre-treatment from P1-5, ethanol (6 g/kg) or Intralipid® on P5, C or S post-treatment from P6-20. On P30, balance and coordination were tested using the dowel crossing test. Overall, there was a significant effect of treatment and females crossed longer distances than males. Ethanol exposure significantly reduced the total distance crossed. Choline pre-treatment increased the distance crossed by males, and both pre- and post-treatment with choline significantly increased total distance crossed for females and males. There was no effect of choline on Intralipid®-exposed animals. This is the first study to show that choline ameliorates ethanol-induced effects on balance and coordination when given before ethanol exposure. Choline fortification of common foodstuffs may reduce the effects of alcohol. PMID:26085462

  7. Intake of fermented beverages protect against acute myocardial injury: target organ cardiac effects and vasculoprotective effects.

    PubMed

    Vilahur, Gemma; Casani, Laura; Guerra, Jose M; Badimon, Lina

    2012-09-01

    Mild-to-moderate alcohol consumption has been associated with reduced risk of morbi/mortality from coronary artery disease. However, whether beer intake affords cardioprotection remains unclear. We investigated whether beer intake (alcohol-containing and alcohol-free brew) provides cardioprotection in a pig model of myocardial infarction (MI). Pigs were randomly assigned to: (1) be fed for 10 days a high-cholesterol diet (HC); (2) HC + low-dose beer (LB; 12.5 g alcohol/day); (3) HC + moderate-dose beer (MB; 25 g alcohol/day); or IV) HC + alcohol-free-MB (0.0 g alcohol/day) before MI induction and kept 21 days with the same regime. Scar size, echocardiography, biochemical and oxidative parameters were assessed. Myocardial tissue was obtained for molecular analysis and histology. All beer-fed animals were less prone to arrhythmogenesis during ischemia. At sacrifice, beer intake was associated with lower oxidative stress and higher HDL-antioxidant capacity. Within the ischemic myocardium beer-fed animals showed higher Akt/eNOS and AMPK activation and reduced sirtuin1-related apoptosis. Compared to controls beer intake was associated with lower lipid infiltration, higher TGFβ-related collagen fibril formation and diminished MMP9 activity in the fibrous tissue limiting scar size (HC + LB and HC + MB P < 0.05 and HC + alcohol-free-MB P = 0.068 vs. HC). Systolic-related parameters were similarly worsen post-MI in all groups and further deteriorated in control animals (P ≤ 0.05 vs. post-MI). At sacrifice, all animals showed a worsening in diastolic-related parameters but overall cardiac performance was improved in beer-fed animals regardless of the dose or alcohol content (P ≤ 0.05). In conclusion, beer intake reduces oxidative stress and apoptosis, activates RISK components and favors reparative fibrosis improving global cardiac performance. PMID:22878829

  8. Gas chromatography-mass spectrometry of ethyl palmitate calibration and resolution with ethyl oleate as biomarker ethanol sub acute in urine application study

    NASA Astrophysics Data System (ADS)

    Suaniti, Ni Made; Manurung, Manuntun

    2016-03-01

    Gas Chromatography-Mass Spectrometry is used to separate two and more compounds and identify fragment ion specific of biomarker ethanol such as palmitic acid ethyl ester (PAEE), as one of the fatty acid ethyl esters as early detection through conyugated reaction. This study aims to calibrate ethyl palmitate and develop analysis with oleate acid. This methode can be used analysis ethanol and its chemistry biomarker in ethanol sub-acute consumption as analytical forensic toxicology. The result show that ethanol level in urine rats Wistar were 9.21 and decreased 6.59 ppm after 48 hours consumption. Calibration curve of ethyl palmitate was y = 0.2035 x + 1.0465 and R2 = 0.9886. Resolution between ethyl palmitate and oleate were >1.5 as good separation with fragment ion specific was 88 and the retention time was 18 minutes.

  9. Acute Toxicity and Gastroprotection Studies of a New Schiff Base Derived Copper (II) Complex against Ethanol-Induced Acute Gastric Lesions in Rats

    PubMed Central

    Hassandarvish, Pouya; Gwaram, Nura Suleiman; A. Hadi, A. Hamid; Mohd Ali, Hapipah; Majid, Nazia; Abdulla, Mahmood Ameen

    2012-01-01

    Background Copper is an essential element in various metabolisms. The investigation was carried out to evaluate acute gastroprotective effects of the Copper (II) complex against ethanol-induced superficial hemorrhagic mucosal lesions in rats. Methodology/Principal Findings Rats were divided into 7 groups. Groups 1 and 2 were orally administered with Tween 20 (10% v/v). Group 3 was orally administered with 20 mg/kg omeprazole (10% Tween 20). Groups 4–7 received 10, 20, 40, and 80 mg/kg of the complex (10% Tween 20), respectively. Tween 20 (10% v/v) was given orally to group 1 and absolute ethanol was given orally to groups 2–7, respectively. Rats were sacrificed after 1 h. Group 2 exhibited severe superficial hemorrhagic mucosal lesions. Gastric wall mucus was significantly preserved by the pre-treatment complex. The results showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histology showed marked reduction of hemorrhagic mucosal lesions in groups 4–7. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. PAS staining of groups 4–7 showed intense stain uptake of gastric mucosa. The acute toxicity revealed the non-toxic nature of the compound. Conclusions/Significance The gastroprotective effect of the Copper (II) complex may possibly be due to preservation of gastric wall mucus; increase in PGE2 synthesis; GSH, SOD, and NO up-regulation of Hsp70 protein; decrease in MDA level; and down-regulation of Bax protein. PMID:23251568

  10. Reduced Sleep Acutely Influences Sedentary Behavior and Mood But Not Total Energy Intake in Normal-Weight and Obese Women.

    PubMed

    Romney, Lora; Larson, Michael J; Clark, Tyler; Tucker, Larry A; Bailey, Bruce W; LeCheminant, James D

    2016-01-01

    Using a crossover design, 22 normal-weight and 22 obese women completed two free-living sleep conditions: (a) Normal Sleep: night of ~8 hr time in bed; and (b) Reduced Sleep: night of < 5 hr time in bed). Outcome measures were energy intake, physical activity and sedentary time, and mood. Sleep time was 7.7 ± 0.3 and 4.8 ± 0.2 hrs during the Normal Sleep and Reduced Sleep conditions, respectively (F = 1791.94; p < 0.0001). Energy intake did not differ between groups or as a function of sleep condition (F = 2.46; p = 0.1244). Sedentary time was ~ 30 min higher after the Reduced Sleep condition (F = 4.98; p = 0.0318); other physical activity outcomes were not different by condition (p > 0.05). Total mood score, depression, anger, vigor, fatigue, and confusion were worse after Reduced Sleep (p < 0.05). Reducing sleep acutely and negatively influenced sedentary time and mood in normal-weight and obese women. PMID:26485109

  11. A Standardized Composition from Extracts of Myristica Fragrans, Astragalus Membranaceus, and Poria Cocos Protects Liver from Acute Ethanol Insult.

    PubMed

    Yimam, Mesfin; Jiao, Ping; Hong, Mei; Jia, Qi

    2016-08-01

    Despite the promising advances in therapeutic discovery, there still is a major challenge in the development of a safe, effective, and economical intervention for managing alcohol-related liver disorders. In this study, we describe the potential use of "MAP," a standardized composition comprising three extracts from Myristica fragrans, Astragalus membranaceus, and Poria cocos, in ameliorating alcohol-induced acute liver toxicity. Ethanol-induced acute hepatotoxicity as an animal model of binge drinking was utilized. Mice received oral doses of MAP at 300 mg/kg for four consecutive days. Mice were orally gavaged with 50% ethanol in 12 mL/kg dosing volume following the third dose of MAP every 12 h thereafter for a total of three doses. Hepatic functional tests from serum collected at T12, and hepatic glutathione (GSH), superoxide dismutases (SODs), and triglyceride from liver homogenates were evaluated. Histopathology analysis and alcoholic steatohepatitis (ASH) scoring were also determined. Excessive increases of serum alanine aminotransferase and aspartate aminotransferase were significantly inhibited at 46.3% and 43.6%, respectively, when mice were treated with MAP. MAP replenished the depleted SOD by more than 60%, while causing significant stimulation of GSH productions. MAP showed statistically significant reduction in ballooning degeneration, vascular steatosis, cytoplasmic or nuclear condensation, and shrinkage, as well as inflammations when compared to vehicle-treated alcohol-induced liver toxicity model. Mice treated with MAP showed statistically significant reduction in ASH scoring when compared to vehicle control. Therefore, the composition MAP could be potentially utilized as an effective hepatic-detoxifying agent for the protection of liver damage caused by alcohol consumptions. PMID:27355692

  12. Acute and long-term effects of alkaloid extract of Mitragyna speciosa on food and water intake and body weight in rats.

    PubMed

    Kumarnsit, Ekkasit; Keawpradub, Niwat; Nuankaew, Watcharin

    2006-07-01

    Acute administration of Mitragyna speciosa (MS) extract (45 and 50 mg/kg) significantly resulted in dose-dependent decreases in food and water intakes (P<0.05) in rats. Prolonged suppressing effects were observed following administration of the MS extract (40 mg/kg) for 60 consecutive days. Moreover, the long-term administration also significantly suppressed weight gaining. PMID:16781828

  13. Function of the corpus luteum in beef heifers is affected by acute submaintenance feeding but is not correlated with residual feed intake

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seventy-four Angus and Angus x Hereford heifers were used in two successive years (yr 1, n = 43; yr 2, n = 31) to determine if ovarian function of heifers during acute submaintenance feeding is related to variation in utilization of feed as determined by residual feed intake (RFI). Residual feed in...

  14. Chronic effects of maternal ethanol and low-protein intake on growth and blood measurements of beagle pups

    SciTech Connect

    Switzer, B.R.; Anderson, J.J.B.; Pick, J.R.

    1986-05-01

    Pups used in this study were born to nulliparous, purebred female beagles fed either 17% control (CP) or 8.5% low protein (LP) diets and were given twice daily either 1.8 g/kg ethanol (E) or an equivalent isocaloric dose of sucrose (S) throughout pregnancy. After parturition, all mothers were fed the CP diet and no E or S. On day 1 and each week up to 4 weeks, the weight (WT), crown-rump length (LT) and head circumference (HC) of the pups were measured. These measurements were taken for a post-weaning subset at 6, 8 and 10 weeks. Blood samples were collected each week. At birth, mean WT, LT and HC were significantly lower in pups from E-mothers as compared to S-mothers with either CP or LP diets. The birth WT, LT and HC were significantly lower when mothers were fed LP as compared to the CP diet with either S or E. The prenatal effects of E and LP were significantly associated with lower pup WT, HT and hematocrit values, but not HC up to 4 weeks. At 10 weeks, the growth measurements and hematocrits were significantly lower with prenatal E exposure but not with LP. Pup red cell levels of folate were significantly lower with prenatal E during the first 4 weeks, whereas the effect of prenatal LP but not E was significant at 10 weeks. These data suggest that growth parameters and hematocrit values of pups prenatally exposed to E do not catch up to those of pups from S-mothers fed either diet.

  15. Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice

    PubMed Central

    Buckman, Laura B.; Thompson, Misty M.; Lippert, Rachel N.; Blackwell, Timothy S.; Yull, Fiona E.; Ellacott, Kate L.J.

    2014-01-01

    Objective Introduction of a high-fat diet to mice results in a period of voracious feeding, known as hyperphagia, before homeostatic mechanisms prevail to restore energy intake to an isocaloric level. Acute high-fat diet hyperphagia induces astrocyte activation in the rodent hypothalamus, suggesting a potential role of these cells in the homeostatic response to the diet. The objective of this study was to determine physiologic role of astrocytes in the acute homeostatic response to high-fat feeding. Methods We bred a transgenic mouse model with doxycycline-inducible inhibition of NFkappaB (NFκB) signaling in astrocytes to determine the effect of loss of NFκB-mediated astrocyte activation on acute high-fat hyperphagia. ELISA was used to measure the levels of markers of astrocyte activation, glial-fibrillary acidic protein (GFAP) and S100B, in the medial basal hypothalamus. Results Inhibition of NFκB signaling in astrocytes prevented acute high-fat diet-induced astrocyte activation and resulted in a 15% increase in caloric intake (P < 0.01) in the first 24 h after introduction of the diet. Conclusions These data reveal a novel homeostatic role for astrocytes in the acute physiologic regulation of food intake in response to high-fat feeding. PMID:25685690

  16. Nongenomic effects of estrogen mediate the dose-related myocardial oxidative stress and dysfunction caused by acute ethanol in female rats

    PubMed Central

    El-Mas, Mahmoud M.

    2013-01-01

    Acute ethanol lowers blood pressure (BP) and cardiac output in proestrus and after chronic estrogen (E2) replacement in ovariectomized (OVX) female rats. However, whether rapid nongenomic effects of estrogen mediate these hemodynamic effects of ethanol remains unanswered. To test this hypothesis, we investigated the effect of ethanol (0.5 or 1.5 g/kg iv) on left ventricular (LV) function and oxidative markers in OVX rats pretreated 30 min earlier with 1 μg/kg E2 (OVXE2) or vehicle (OVX) and in proestrus sham-operated (SO) rats. In SO rats, ethanol caused significant and dose-related reductions in BP, rate of rise in LV pressure (LV dP/dtmax), and LV developed pressure (LVDP). These effects of ethanol disappeared in OVX rats and were restored in OVXE2 rats, suggesting rapid estrogen receptor signaling mediates the detrimental effects of ethanol on LV function. Ex vivo studies revealed that the estrogen-dependent myocardial dysfunction caused by ethanol was coupled with higher LV 1) generation of reactive oxygen species (ROS), 2) expression of malondialdehyde and 4-hydroxynonenal protein adducts, 3) phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinases (ERK1/2), and 4) catalase activity. ERK1/2 inhibition by PD-98059 (1 mg/kg iv) abrogated the myocardial dysfunction, hypotension, and the elevation in myocardial ROS generation caused by ethanol. We conclude that rapid estrogen receptor signaling is implicated in cellular events that lead to the generation of aldehyde protein adducts and Akt/ERK1/2 phosphorylation, which ultimately mediate the estrogen-dependent LV oxidative stress and dysfunction caused by ethanol in female rats. PMID:24368668

  17. Antitumor activity of ethanol extract from Hippophae rhamnoides L. leaves towards human acute myeloid leukemia cells in vitro.

    PubMed

    Zhamanbaeva, G T; Murzakhmetova, M K; Tuleukhanov, S T; Danilenko, M P

    2014-12-01

    We studied the effects of ethanol extract from Hippophae rhamnoides L. leaves on the growth and differentiation of human acute myeloid leukemia cells (KG-1a, HL60, and U937). The extract of Hippophae rhamnoides L. leaves inhibited cell growth depending on the cell strain and extract dose. In a high concentration (100 μg/ml), the extract also exhibited a cytotoxic effect on HL60 cells. Hippophae rhamnoides L. leaves extract did not affect cell differentiation and did not modify the differentiating effect of calcitriol, active vitamin D metabolite. Inhibition of cell proliferation was paralleled by paradoxical accumulation of phase S cells (synthetic phase) with a reciprocal decrease in the count of G1 cells (presynthetic phase). The extract in a concentration of 100 μg/ml induced the appearance of cells with a subdiploid DNA content (sub-G1 phase cells), which indicated induction of apoptosis. The antiproliferative effect of Hippophae rhamnoides L. extract on acute myeloid leukemia cells was at least partially determined by activation of the S phase checkpoint, which probably led to deceleration of the cell cycle and apoptosis induction. PMID:25432283

  18. Herbal SGR Formula Prevents Acute Ethanol-Induced Liver Steatosis via Inhibition of Lipogenesis and Enhancement Fatty Acid Oxidation in Mice.

    PubMed

    Qiu, Ping; Li, Xiang; Kong, De-Song; Li, Huan-Zhou; Niu, Cong-Cong; Pan, Su-Hua

    2015-01-01

    Our previous study indicated that herbal SGR formula partially attenuates ethanol-induced fatty liver, but the underlying mechanisms remain unclear. In the present study, mice were pretreated with SGR (100 and 200 mg/kg/d bw) for 30 d before being exposed to ethanol (4.8 g/kg bw). The biochemical indices and histopathological changes were examined to evaluate the protective effects and to explore potential mechanisms by investigating the adiponectin, tumor necrosis factor-α (TNF-α), peroxisome proliferators-activated receptor-α (PPAR-α), sterol regulatory element binding protein-1c (SREBP-1c), adenosine monophosphate-activated protein kinase (AMPK), and so forth. Results showed that SGR pretreatment markedly inhibited acute ethanol-induced liver steatosis, significantly reduced serum and hepatic triglyceride (TG) level, and improved classic histopathological changes. SGR suppressed the protein expression of hepatic SREBP-1c and TNF-α and increased adiponectin, PPAR-α, and AMPK phosphorylation in the liver. Meanwhile, acute toxicity tests showed that no death or toxic side effects within 14 days were observed upon oral administration of the extracts at a dose of 16 g/kg body wt. These results demonstrate that SGR could protect against acute alcohol-induced liver steatosis without any toxic side effects. Therefore, our studies provide novel molecular insights into the hepatoprotective effect of SGR formula, which may be exploited as a therapeutic agent for ethanol-induced hepatosteatosis. PMID:26101535

  19. Herbal SGR Formula Prevents Acute Ethanol-Induced Liver Steatosis via Inhibition of Lipogenesis and Enhancement Fatty Acid Oxidation in Mice

    PubMed Central

    Qiu, Ping; Li, Xiang; Kong, De-song; Li, Huan-zhou; Niu, Cong-cong; Pan, Su-hua

    2015-01-01

    Our previous study indicated that herbal SGR formula partially attenuates ethanol-induced fatty liver, but the underlying mechanisms remain unclear. In the present study, mice were pretreated with SGR (100 and 200 mg/kg/d bw) for 30 d before being exposed to ethanol (4.8 g/kg bw). The biochemical indices and histopathological changes were examined to evaluate the protective effects and to explore potential mechanisms by investigating the adiponectin, tumor necrosis factor-α (TNF-α), peroxisome proliferators-activated receptor-α (PPAR-α), sterol regulatory element binding protein-1c (SREBP-1c), adenosine monophosphate-activated protein kinase (AMPK), and so forth. Results showed that SGR pretreatment markedly inhibited acute ethanol-induced liver steatosis, significantly reduced serum and hepatic triglyceride (TG) level, and improved classic histopathological changes. SGR suppressed the protein expression of hepatic SREBP-1c and TNF-α and increased adiponectin, PPAR-α, and AMPK phosphorylation in the liver. Meanwhile, acute toxicity tests showed that no death or toxic side effects within 14 days were observed upon oral administration of the extracts at a dose of 16 g/kg body wt. These results demonstrate that SGR could protect against acute alcohol-induced liver steatosis without any toxic side effects. Therefore, our studies provide novel molecular insights into the hepatoprotective effect of SGR formula, which may be exploited as a therapeutic agent for ethanol-induced hepatosteatosis. PMID:26101535

  20. Acute obtundation in a 9-month-old patient: ethanol ingestion.

    PubMed

    Edmunds, Suzanne M; Ajizian, Samuel J; Liguori, Anthony

    2014-10-01

    Alcohol ingestion in the pediatric patient can be life threatening. Younger patients consume larger volumes per body weight with accidental ingestions, and children have more serious adverse effects at lower blood alcohol levels. Complications of alcohol poisoning can include hypothermia, hypoglycemia, seizures, coma, and death. We present the course of a 9-month-old female infant who became unresponsive at home and presented to the emergency department comatose. When her blood alcohol level registered 489 mg/dL, it was revealed that she had accidentally been given a bottle of formula mixed with vodka rather than water. The infant required intubation for severely depressed level of consciousness and aggressive fluid resuscitation for hemodynamic instability. She had a peak lactate level of 24 mmol/L and a peak blood alcohol level of 524 mg/dL. Based on the severity of her initial presentation, preparations were made for hemodialysis. The infant responded to supportive measures including mechanical ventilation, fluids, and dextrose, and hemodialysis was not necessary. Her alcohol clearance followed zero-order kinetics at an average rate of 28.6 mg/dL per hour over 15.5 hours from her peak level of 524 mg/dL to the lowest measured value of 80 mg/dL. The kinetics of ethanol clearance at this level of toxicity, which is the highest reported in an infant to date, enhance our knowledge of ethanol metabolism and will assist in management decisions in cases of severe intoxication. PMID:25275356

  1. Spin-trapping studies of hepatic free radicals formed following the acute administration of ethanol to rats: In vivo detection of 1-hydroxyethyl radicals with PBN

    SciTech Connect

    Reinke, L.A.; Kotake, Y.; McCay, P.B.; Janzen, E.G. )

    1991-01-01

    The generation of free radicals in rat liver following the acute oral administration of ethanol was studied with the spin-trapping method, using a deuterated derivative of phenyl-N-tert-butylnitrone (PBN-d14) as the spin-trapping agent. After administration of ethanol and PBN-d14 to rats, organic extracts of the liver were prepared and subjected to ESR spectroscopy. In the case of ethanol-treated rats, the ESR spectra indicated that mixtures of radicals had been trapped, while spectra from control rats were essentially negative. The predominant spin adduct detected after ethanol treatment is proposed to be from a carbon-centered, primary alkyl radical, based on gamma-hydrogen hyperfine splitting patterns observed with PBN-d14. Oxygen-centered radicals also contributed to the ESR spectra. Liver extracts also contained low concentrations of the 1-hydroxyethyl radical spin adduct, which was indicated by weak spectral lines corresponding to those of the 1-13C-ethanol adduct. These data confirm previous suggestions that ethanol is metabolized to a free radical metabolite in rat liver. In addition, some information on types of lipid radicals generated during alcohol intoxication has been obtained.

  2. Phytochemical and acute toxicity of ethanolic extract of Enantia chlorantha (oliv) stem bark in albino rats

    PubMed Central

    Abatan, Mathew O.

    2013-01-01

    It is presumed that drugs sourced from herbs have lesser side effects than allopathic drugs. Enantia chlorantha is widely used in herbal medicine for the treatment of several ailments such as jaundice, malaria, fever, infective hepatitis, etc. However its toxicity profiles are not well documented. The effects of ethanolic extract of E. chlorantha stem bark on body weight changes, biochemical and haematological parameters as well as histology of vital organs (heart, kidneys and liver) were assessed. Also, the phytochemical constituent of the plant was analysed. Albino rats of both sexes were randomly divided into five groups (A–E) of five rats each and the ethanolic extract of E. chlorantha stem bark extract was administered by oral gavage in a single dose. Group A rats were administered 500 mg/kg of the extract, group B; 1000 mg/kg, group C; 2000 mg/kg, group D; 3000 mg/kg and group E rats received distilled water (10 ml/kg) and served as control. The extract caused significant (p<0.05) decreases in the levels of packed cell volume, haemoglobin concentration and red blood cell counts in a dose dependent manner. Further, significant alterations were not observed in the serum biochemical parameters analysed (AST, ALP, ALT, blood urea nitrogen, total protein, albumin, globulin and bilirubin). In addition, the extract at 1000, 2000 and 3000 mg/kg caused congestion in the heart and kidney of experimental rats. These results suggest that oral administration of E. chlorantha may produce severe toxic effects at relatively high doses, thus caution should be exercised in its use. PMID:24678252

  3. [A case of acute ethanol intoxication with remarkable hyperglycemia by "ume-shu", a Japanese apricot liquor made with a large amount of sugar].

    PubMed

    Sugano, Takayuki; Kojima, Naoki; Kaneko, Susumu; Ishida, Junro; Terada, Taizo; Inagawa, Hiroshi; Okada, Yasusei

    2002-07-01

    A 19-year-old woman ingested 2.2 L of "umeshu", a Japanese apricot liquor made with a large amount of sugar. She was unconscious and in shock. The estimated blood ethanol concentration was 607 mg/dl, and the blood glucose level was 576 mg/dl. Because her respiration and circulation was highly suppressed, blood purification was indicated. Continuous hemodiafiltration (CHDF) was performed instead of hemodialysis because her hemodynamics was unstable. After CHDF was instituted, her blood glucose level reduced to normal range, and her consciousness became alert. CHDF was effective in eliminating ethanol and stabilizing her hemodynamics within an early stage. Though acute ethanol intoxication is known to inhibit glucogenesis, leading to hypoglycemia, marked hyperglycemia was seen in this case. Ingestion of a large amount of glucose-rich liquor and being in shock seemed to be the causes of hyperglycemia. PMID:12415871

  4. Dietary flaxseed intake exacerbates acute colonic mucosal injury and inflammation induced by dextran sodium sulfate.

    PubMed

    Zarepoor, Leila; Lu, Jenifer T; Zhang, Claire; Wu, Wenqing; Lepp, Dion; Robinson, Lindsay; Wanasundara, Janitha; Cui, Steve; Villeneuve, Sébastien; Fofana, Bourlaye; Tsao, Rong; Wood, Geoffrey A; Power, Krista A

    2014-06-15

    Flaxseed (FS), a dietary oilseed, contains a variety of anti-inflammatory bioactives, including fermentable fiber, phenolic compounds (lignans), and the n-3 polyunsaturated fatty acid (PUFA) α-linolenic acid. The objective of this study was to determine the effects of FS and its n-3 PUFA-rich kernel or lignan- and soluble fiber-rich hull on colitis severity in a mouse model of acute colonic inflammation. C57BL/6 male mice were fed a basal diet (negative control) or a basal diet supplemented with 10% FS, 6% kernel, or 4% hull for 3 wk prior to and during colitis induction via 5 days of 2% (wt/vol) dextran sodium sulfate (DSS) in their drinking water (n = 12/group). An increase in anti-inflammatory metabolites (hepatic n-3 PUFAs, serum mammalian lignans, and cecal short-chain fatty acids) was associated with consumption of all FS-based diets, but not with anti-inflammatory effects in DSS-exposed mice. Dietary FS exacerbated DSS-induced acute colitis, as indicated by a heightened disease activity index and an increase in colonic injury and inflammatory biomarkers [histological damage, apoptosis, myeloperoxidase, inflammatory cytokines (IL-6 and IL-1β), and NF-κB signaling-related genes (Nfkb1, Ccl5, Bcl2a1a, Egfr, Relb, Birc3, and Atf1)]. Additionally, the adverse effect of the FS diet was extended systemically, as serum cytokines (IL-6, IFNγ, and IL-1β) and hepatic cholesterol levels were increased. The adverse effects of FS were not associated with alterations in fecal microbial load or systemic bacterial translocation (endotoxemia). Collectively, this study demonstrates that although consumption of a 10% FS diet enhanced the levels of n-3 PUFAs, short-chain polyunsaturated fatty acids, and lignans in mice, it exacerbated DSS-induced colonic injury and inflammation. PMID:24763556

  5. Chronic Intermittent Ethanol Inhalation Increases Ethanol Self-administration in both C57BL/6J and DBA/2J Mice

    PubMed Central

    McCool, Brian A.; Chappell, Ann M.

    2015-01-01

    Inbred mouse strains provide significant opportunities to understand the genetic mechanisms controlling ethanol-directed behaviors and neurobiology. They have been specifically employed to understand cellular mechanisms contributing to ethanol consumption, acute intoxication, and sensitivities to chronic effects. However, limited ethanol consumption by some strains has restricted our understanding of clinically relevant endpoints such as dependence-related ethanol intake. Previous work with a novel tastant-substitution procedure using monosodium glutamate (MSG or umami flavor) has shown that the procedure greatly enhances ethanol consumption by mouse strains that express limited drinking phenotypes using other methods. In the current study, we employ this MSG-substitution procedure to examine how ethanol dependence, induced with passive vapor inhalation, modifies ethanol drinking in C57BL/6J and DBA/2J mice. These strains represent ‘high’ and ‘low’ drinking phenotypes, respectively. We found that the MSG substitution greatly facilitates ethanol drinking in both strains, and likewise, ethanol dependence increased ethanol consumption regardless of strain. However, DBA/2J mice exhibited greater sensitivity dependence-enhanced drinking, as represented by consumption behaviors directed at lower ethanol concentrations and relative to baseline intake levels. DBA/2J mice also exhibited significant withdrawal-associated anxiety-like behavior while C57BL/6J mice did not. These findings suggest that the MSG-substitution procedure can be employed to examine dependence-enhanced ethanol consumption across a range of drinking phenotypes, and that C57BL/6J and DBA/2J mice may represent unique neurobehavioral pathways for developing dependence-enhanced ethanol consumption. PMID:25659650

  6. Environmental stressors influence limited-access ethanol consumption by C57BL/6J mice in a sex-dependent manner

    PubMed Central

    Cozzoli, Debra K.; Tanchuck-Nipper, Michelle A.; Kaufman, Moriah N.; Horowitz, Chloe B.; Finn, Deborah A.

    2015-01-01

    correlated with subsequent ethanol intake. In summary, the type of stressor administered had a profound impact on subsequent ethanol consumption, with subtle sex differences in the magnitude and persistence of the effect. These findings are the first to demonstrate that a single, acute exposure to restraint, tail suspension, and predator odor stress increased plasma CORT and ALLO levels in animals with a history of ethanol consumption and that female mice were more responsive than males to the ability of stress to increase CORT levels as well as to the ability of predator odor stress to produce a delayed increase in ethanol intake. Because predator odor stress is a model of posttraumatic stress disorder, the present sex differences have important implications for future preclinical studies modeling the comorbidity of posttraumatic stress disorder and alcohol use disorders. PMID:25459519

  7. Prooxidant activity of norbixin in model of acute gastric ulcer induced by ethanol in rats.

    PubMed

    Rovani, B T; de Freitas, R B; Augusti, P R; Araldi, I C; Somacal, S; Quatrin, A; Emanuelli, T; da Rocha, M P; Bauermann, L de Freitas

    2016-07-01

    Free radicals and oxidative stress play a central role in gastric injuries caused by ethanol (EtOH). Antioxidant strategies to counteract EtOH toxicity are highly desirable. Norbixin (NBIX) is a carotenoid with antioxidant potential largely used in the food industry. This study evaluated the NBIX effects in a model of gastric ulcer induced by EtOH in rats. Male Wistar rats received NBIX doses of 0, 10, and 25 mg/kg by gavage 1 h after EtOH administration (0 or 75% solution, 1 mL/200 g of animal). The animals were euthanized 1 h after the NBIX administration, and their stomachs were removed for macroscopic and histopathological analyses, quantification of nonprotein sulfhydryl (NPSH) groups, lipid peroxidation (LPO) levels, and catalase (CAT) activity determination. NBIX increased LPO in gastric mucosa and caused CAT inhibition and NPSH depletion in EtOH-treated animals. Results showed that NBIX did not protect gastric tissue against EtOH damage, and this could be associated to a prooxidant effect. PMID:26353805

  8. The acute effects of daily nicotine intake on heart rate--a toxicokinetic and toxicodynamic modelling study.

    PubMed

    Gajewska, M; Worth, A; Urani, C; Briesen, H; Schramm, K-W

    2014-10-01

    Joint physiologically-based toxicokinetic and toxicodynamic (PBTK/TD) modelling was applied to simulate concentration-time profiles of nicotine, a well-known stimulant, in the human body following single and repeated dosing. Both kinetic and dynamic models were first calibrated by using in vivo literature data for the Caucasian population. The models were then used to estimate the blood and liver concentrations of nicotine in terms of the Area Under Curve (AUC) and the peak concentration (Cmax) for selected exposure scenarios based on inhalation (cigarette smoking), oral intake (nicotine lozenges) and dermal absorption (nicotine patches). The model simulations indicated that whereas frequent cigarette smoking gives rise to high AUC and Cmax in blood, the use of nicotine-rich dermal patches leads to high AUC and Cmax in the liver. Venous blood concentrations were used to estimate one of the most common acute effects, mean heart rate, both at rest and during exercise. These estimations showed that cigarette smoking causes a high peak heart rate, whereas dermal absorption causes a high mean heart rate over 48h. This study illustrates the potential of using PBTK/TD modelling in the safety assessment of nicotine-containing products. PMID:25066669

  9. [Pharmacological correction of toxic liver damage in patients with heavy forms of acute ethanol intoxication].

    PubMed

    Shikalova, I A; Shilov, V V; Vasil'ev, S A; Batotsyrenov, B V; Loladze, A T

    2012-01-01

    The efficiency of using remaxol and ademethionine in the therapy of patients with heavy acute alcohol intoxication on the background of toxic liver damage has been studied. The administration of remaxol led to improvement of the clinical treatment of alcohol intoxication, which is manifested by a decrease in the rate and duration of delirium tremens (from 33.9 to 10.8%), frequency of secondary lung disorders (from 18.5 to 3.1%), duration of stay in hospital (from 7.3 +/- 0.6 to 5.6 +/- 0.3 days), and total therapy duration (from 11.8 +/- 1.05 to 5.6 +/- 0.3 days). The results of biochemical investigations confirmed that remaxol and ademethionine provide effective treatment of the toxic liver damage. Remaxol decreases the degree of metabolic disorders to a greater extent than does ademethionine. PMID:22702109

  10. Effect of acute ethanol on beta-endorphin secretion from rat fetal hypothalamic neurons in primary cultures

    SciTech Connect

    Sarkar, D.K.; Minami, S. )

    1990-01-01

    To characterize the effect of ethanol on the hypothalamic {beta}-endorphin-containing neurons, rat fetal hypothalamic neurons were maintained in primary culture, and the secretion of {beta}-endorphin ({beta}-EP) was determined after ethanol challenges. Constant exposure to ethanol at doses of 6-50 mM produced a dose-dependent increase in basal secretion of {beta}-EP from these cultured cells. These doses of ethanol did not produce any significant effect on cell viability, DNA or protein content. The stimulated secretion of {beta}-EP following constant ethanol exposure is short-lasting. However, intermittent ethanol exposures maintained the ethanol stimulatory action on {beta}-EP secretion for a longer time. The magnitude of the {beta}-EP response to 50 mM ethanol is similar to that of the {beta}-EP response to 56 mM of potassium. Ethanol-stimulated {beta}-EP secretion required extracellular calcium and was blocked by a calcium channel blocker; a sodium channel blocker did not affect ethanol-stimulated secretion. These results suggest that the neuron culture system is a useful model for studying the cellular mechanisms involved in the ethanol-regulated hypothalamic opioid secretion.

  11. Brain plasticity and cognitive functions after ethanol consumption in C57BL/6J mice.

    PubMed

    Stragier, E; Martin, V; Davenas, E; Poilbout, C; Mongeau, R; Corradetti, R; Lanfumey, L

    2015-01-01

    Acute or chronic administrations of high doses of ethanol in mice are known to produce severe cognitive deficits linked to hippocampal damage. However, we recently reported that chronic and moderate ethanol intake in C57BL/6J mice induced chromatin remodeling within the Bdnf promoters, leading to both enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis under free-choice protocol. We performed here a series of cellular and behavioral studies to analyze the consequences of these modifications. We showed that a 3-week chronic free-choice ethanol consumption in C57BL/6J mice led to a decrease in DNA methylation of the Bdnf gene within the CA1 and CA3 subfields of the hippocampus, and upregulated hippocampal BDNF signaling pathways mediated by ERK, AKT and CREB. However, this activation did not affect long-term potentiation in the CA1. Conversely, ethanol intake impaired learning and memory capacities analyzed in the contextual fear conditioning test and the novel object recognition task. In addition, ethanol increased behavioral perseveration in the Barnes maze test but did not alter the mouse overall spatial capacities. These data suggested that in conditions of chronic and moderate ethanol intake, the chromatin remodeling leading to BDNF signaling upregulation is probably an adaptive process, engaged via epigenetic regulations, to counteract the cognitive deficits induced by ethanol. PMID:26670281

  12. Acute and chronic intakes of fallout radionuclides by Marshallese from nuclear weapons testing at Bikini and Enewetak and related internal radiation doses.

    PubMed

    Simon, Steven L; Bouville, André; Melo, Dunstana; Beck, Harold L; Weinstock, Robert M

    2010-08-01

    Annual internal radiation doses resulting from both acute and chronic intakes of all important dose-contributing radionuclides occurring in fallout from nuclear weapons testing at Bikini and Enewetak from 1946 through 1958 have been estimated for the residents living on all atolls and separate reef islands of the Marshall Islands. Internal radiation absorbed doses to the tissues most at risk to cancer induction (red bone marrow, thyroid, stomach, and colon) have been estimated for representative persons of all population communities for all birth years from 1929 through 1968, and for all years of exposure from 1948 through 1970. The acute intake estimates rely on a model using, as its basis, historical urine bioassay data, for members of the Rongelap Island and Ailinginae communities as well as for Rongerik residents. The model also utilizes fallout times of arrival and radionuclide deposition densities estimated for all tests and all atolls. Acute intakes of 63 radionuclides were estimated for the populations of the 20 inhabited atolls and for the communities that were relocated during the testing years for reasons of safety and decontamination. The model used for chronic intake estimates is based on reported whole-body, urine, and blood counting data for residents of Utrik and Rongelap. Dose conversion coefficients relating intake to organ absorbed dose were developed using internationally accepted models but specifically tailored for intakes of particulate fallout by consideration of literature-based evidence to choose the most appropriate alimentary tract absorption fraction (f1) values. Dose estimates were much higher for the thyroid gland than for red marrow, stomach wall, or colon. The highest thyroid doses to adults were about 7,600 mGy for the people exposed on Rongelap; thyroid doses to adults were much lower, by a factor of 100 or more, for the people exposed on the populated atolls of Kwajalein and Majuro. The estimates of radionuclide intake and

  13. ACUTE AND CHRONIC INTAKES OF FALLOUT RADIONUCLIDES BY MARSHALLESE FROM NUCLEAR WEAPONS TESTING AT BIKINI AND ENEWETAK AND RELATED INTERNAL RADIATION DOSES

    PubMed Central

    Simon, Steven L.; Bouville, André; Melo, Dunstana; Beck, Harold L.; Weinstock, Robert M.

    2014-01-01

    Annual internal radiation doses resulting from both acute and chronic intakes of all important dose-contributing radionuclides occurring in fallout from nuclear weapons testing at Bikini and Enewetak from 1946 through 1958 have been estimated for the residents living on all atolls and separate reef islands of the Marshall Islands. Internal radiation absorbed doses to the tissues most at risk to cancer induction (red bone marrow, thyroid, stomach, and colon) have been estimated for representative persons of all population communities for all birth years from 1929 through 1968, and for all years of exposure from 1948 through 1970. The acute intake estimates rely on a model using, as its basis, historical urine bioassay data, for members of the Rongelap Island and Ailinginae communities as well as for Rongerik residents. The model also utilizes fallout times of arrival and radionuclide deposition densities estimated for all tests and all atolls. Acute intakes of 63 radionuclides were estimated for the populations of the 20 inhabited atolls and for the communities that were relocated during the testing years for reasons of safety and decontamination. The model used for chronic intake estimates is based on reported whole-body, urine, and blood counting data for residents of Utrik and Rongelap. Dose conversion coefficients relating intake to organ absorbed dose were developed using internationally accepted models but specifically tailored for intakes of particulate fallout by consideration of literature-based evidence to choose the most appropriate alimentary tract absorption fraction (f1) values. Dose estimates were much higher for the thyroid gland than for red marrow, stomach wall, or colon. The highest thyroid doses to adults were about 7,600 mGy for the people exposed on Rongelap; thyroid doses to adults were much lower, by a factor of 100 or more, for the people exposed on the populated atolls of Kwajalein and Majuro. The estimates of radionuclide intake and

  14. The effects of ethanol on angiogenesis after myocardial infarction, and preservation of angiogenesis with rosuvastatin after heavy drinking.

    PubMed

    Zhang, Yuying; Yuan, Haitao; Sun, Yongle; Wang, Yong; Wang, Aihong

    2016-08-01

    The cardioprotective effects of moderate alcohol consumption and statins have been known for years. However, heavy or binge drinking confers a high risk of cardiovascular disease. This study aimed to investigate the effects of different levels of alcohol consumption on acute myocardial infarction that was induced experimentally in rats, with a focus on the potential mechanism of angiogenesis and the effects of statins on heavy drinking. The experimental rats were fed low-dose ethanol (0.5 g/kg/day), high-dose ethanol (5 g/kg/day), and high-dose ethanol with rosuvastatin (10 mg/kg/day) during the entire experiment. Acute myocardial infarctions were induced 4 weeks after the beginning of the experiment. We assessed the capillary density in the myocardium via immunohistochemistry and quantified the expression of vascular endothelial growth factor (VEGF) and endostatin via enzyme-linked immunosorbent assay kits on the 4th day after myocardial infarction. The results revealed that low ethanol consumption promoted angiogenesis in association with higher VEGF and lower endostatin. High ethanol intake suppressed angiogenesis with unchanged VEGF and elevated endostatin. Treatment with rosuvastatin preserved angiogenesis following high ethanol intake, with an upregulation of VEGF. This study highlights that low ethanol consumption obviously promotes angiogenesis in myocardial-infarction rats while increasing the expression of VEGF, whereas high ethanol consumption inhibits ischemia-induced angiogenesis. This study also provides evidence that rosuvastatin alleviates the inhibitory effects of heavy drinking on angiogenesis. PMID:27565753

  15. Understanding of human metabolic pathways of different sub-classes of phenols from Arbutus unedo fruit after an acute intake.

    PubMed

    Mosele, Juana I; Macià, Alba; Motilva, María-José

    2016-03-16

    Arbutus unedo is a small Mediterranean fruit, commonly named strawberry tree, which is a rich source of different sub-classes of phenolic compounds, the more representative being the gallic acid derivatives, including its mono and oligomeric forms esterified with quinic and shikimic acids. In addition, galloyl derivatives, particularly gallotannins, described in A. unedo, are part of a very selective phenolic group, present in a reduced number of plant-products. The aim of the present study is to provide a better understanding of human metabolic pathways of different sub-classes of phenols from the A. unedo fruit after an acute intake by healthy adults. Therefore, the A. unedo phenolic metabolites were studied in whole blood samples (0 to 24 h), urine (24 h) and feces (12 and 24 h). Special focus was placed on the application of dried blood spot (DBS) cards for the sample collection and for the analysis of phenolic metabolites in whole blood samples. The results of the blood analysis revealed two peaks for the maximum concentrations of the main phenolic metabolites. Furthermore, it is appropriate to highlight the application of DBS cards as an efficient and accurate way to collect blood samples in post-prandial bioavailability studies. The analysis of urine (24 h) gave a wide range of phenolic metabolites showing the extensive metabolism that A. unedo phenolic compounds underwent in the human body. The results of the study provide a relevant contribution to the understanding of the in vivo human bioavailability of phenolic compounds, especially galloyl derivatives, a singular phenolic sub-group present in the A. unedo fruit. PMID:26960019

  16. An acute intake of plant stanol esters alters immune-related pathways in the jejunum of healthy volunteers.

    PubMed

    De Smet, Els; Mensink, Ronald P; Boekschoten, Mark V; de Ridder, Rogier; Germeraad, Wilfred T V; Wolfs, Tim G A M; Plat, Jogchum

    2015-03-14

    Plant sterols and stanols inhibit intestinal cholesterol absorption and consequently lower serum LDL-cholesterol (LDL-C) concentrations. The underlying mechanisms are not yet known. In vitro and animal studies have suggested that changes in intestinal sterol metabolism are attributed to the LDL-C-lowering effects of plant stanol esters. However, similar studies in human subjects are lacking. Therefore, we examined the effects of an acute intake of plant stanol esters on gene expression profiles of the upper small intestine in healthy volunteers. In a double-blind cross-over design, fourteen healthy subjects (eight female and six male; age 21-55 years), with a BMI ranging from 21 to 29 kg/m², received in random order a shake with or without plant stanol esters (4 g). At 5 h after consumption of the shake, biopsies were taken from the duodenum (around the papilla of Vater) and from the jejunum (20 cm distal from the papilla of Vater). Microarray analysis showed that the expression profiles of genes involved in sterol metabolism were not altered. Surprisingly, the pathways involved in T-cell functions were down-regulated in the jejunum. Furthermore, immunohistochemical analysis showed that the number of CD3 (cluster of differentiation number 3), CD4 (cluster of differentiation number 4) and Foxp3⁺ (forkhead box P3-positive) cells was reduced in the plant stanol ester condition compared with the control condition, which is in line with the microarray data. The physiological and functional consequences of the plant stanol ester-induced reduction of intestinal T-cell-based immune activity in healthy subjects deserve further investigation. PMID:25683704

  17. Involvement of protein kinase C and Src tyrosine kinase in acute tolerance to ethanol inhibition of spinal NMDA-induced pressor responses in rats

    PubMed Central

    Hsieh, W-K; Lin, H-H; Lai, C-C

    2009-01-01

    Background and purpose: The present study was carried out to examine the role of protein kinases in the development of acute tolerance to the effects of ethanol on spinal N-methyl-D-aspartate (NMDA) receptor-mediated pressor responses during prolonged ethanol exposure. Experimental approach: Blood pressure responses induced by intrathecal injection of NMDA were recorded. The levels of several phosphorylated residues on NMDA receptor NR1 (GluN1) (NR1) and NMDA receptor NR2B (GluN2B) (NR2B) subunits were determined by immunohistochemistry and Western blot analysis. Key results: Ethanol inhibited spinal NMDA-induced pressor responses at 10 min, but the inhibition was significantly reduced at 40 min following continuous infusion. This effect was dose-dependently blocked by chelerythrine [a protein kinase C (PKC) inhibitor, 1–1000 pmol] or PP2 (a Src family tyrosine kinase inhibitor, 1–100 pmol) administered intrathecally 10 min following ethanol infusion. A significant increase in the immunoreactivity of phosphoserine 896 of NR1 subunits (pNR1-Ser896) and phosphotyrosine 1336 of NR2B subunits (pNR2B-Tyr1336) was found in neurons of intermediolateral cell column during the development of tolerance. Levels of pNR1-Ser896 and pNR2B-Tyr1336 were also significantly increased in lateral horn regions of the spinal cord slices incubated with ethanol for 40 min in vitro. The increases in pNR1-Ser896 and pNR2B-Tyr1336 levels were inhibited by post-treatment with chelerythrine and PP2, respectively, both in the in vivo and in vitro studies. Conclusions and implications: The results suggest that activation of PKC and Src tyrosine kinase during prolonged ethanol exposure leading to increases in the levels of pNR1-Ser896 and pNR2B-Tyr1336 may contribute to acute tolerance to inhibition by ethanol of NMDA receptor function. PMID:19703167

  18. Acute ethanol intoxication shows no effect on Ca sup 2+ -uptake of Ca sup 2+ -dependent ATPase activity in myocardial sarcoplasmic reticulum vesicles

    SciTech Connect

    McAllister, K.P.; Horton, J.W.; Kaufman, T.M.; White, D.J. )

    1989-02-09

    We have previously shown that acute ethanolism impairs left ventricular (LV) function. We hypothesized that cardiac dysfunction may be related to altered Ca{sup 2+} pump function by the sarcoplasmic reticulum (SR). In this study, LV function (in isolated perfused hearts) was compared to Ca{sup 2+} transport in SR vesicles isolated from nonperfused hearts in control (C) and acutely intoxicated (ETOH, 2.5 ml/kg IV) guinea pigs. Compared to control hearts, ETOH hearts had significantly lower LV systolic pressure maximal rate of LV pressure rise and fall. Ca{sup 2+}-ATPase activity was not significantly different in either group of animals. Although maximum Ca{sup 2+} uptake tended to be slightly lower in ETOH compared to control hearts coupling ratios (mol Ca{sup 2+} transported/mol ATP hydrolyzed) were not significantly different. We conclude that changes in SR Ca{sup 2+} pump function are not responsible for the depressed LV function seen in acute ethanolism.

  19. Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid.

    PubMed

    Dos Reis Lívero, Francislaine Aparecida; da Silva, Luisa Mota; Ferreira, Daniele Maria; Galuppo, Larissa Favaretto; Borato, Debora Gasparin; Prando, Thiago Bruno Lima; Lourenço, Emerson Luiz Botelho; Strapasson, Regiane Lauriano Batista; Stefanello, Maria Élida Alves; Werner, Maria Fernanda de Paula; Acco, Alexandra

    2016-09-01

    Ethanol is a psychoactive substance highly consumed around the world whose health problems include gastric lesions. Baccharis trimera is used in folk medicine for the treatment of gastrointestinal disorders. However, few studies have evaluated its biological and toxic effects. To validate the popular use of B. trimera and elucidate its possible antiulcerogenic and cytotoxic mechanisms, a hydroethanolic extract of B. trimera (HEBT) was evaluated in models of gastric lesions. Rats and mice were used to evaluate the protective and antiulcerogenic effects of HEBT on gastric lesions induced by ethanol, acetic acid, and chronic ethanol consumption. The effects of HEBT were also evaluated in a pylorus ligature model and on gastrointestinal motility. The LD50 of HEBT in mice was additionally estimated. HEBT was analyzed by nuclear magnetic resonance, and a high-performance liquid chromatography fingerprint analysis was performed. Oral HEBT administration significantly reduced the lesion area and the oxidative stress induced by acute and chronic ethanol consumption. However, HEBT did not protect against gastric wall mucus depletion and did not alter gastric secretory volume, pH, or total acidity in the pylorus ligature model. Histologically, HEBT accelerated the healing of chronic gastric ulcers in rats, reflected by contractions of the ulcer base. Flavonoids and caffeoylquinic acids were detected in HEBT, which likely contributed to the therapeutic efficacy of HEBT, preventing or reversing ethanol- and acetic acid-induced ulcers, respectively. HEBT antiulcerogenic activity may be partially attributable to the inhibition of free radical generation and subsequent prevention of lipid peroxidation. Our results indicate that HEBT has both gastroprotective and curative activity in animal models, with no toxicity. PMID:27314669

  20. Spin trapping of free radical metabolites of carbon tetrachloride in vitro and in vivo: Effect of acute ethanol administration

    SciTech Connect

    Reinke, L.A.; Towner, R.A.; Janzen, E.G. )

    1992-01-01

    A single dose of ethanol, when administered 18 hr prior to CCl4, potentiates the hepatotoxicity of the halocarbon. In these studies, spin trapping and electron spin resonance (ESR) spectroscopy methods were utilized to determine whether a single ethanol dose increased the metabolism of CCl4 to free radical intermediates. When hepatic microsomes from ethanol-treated or control rats were incubated with CCl4 and the spin trapping agent alpha-phenyl-N-tert-butylnitrone (PBN), the ESR signal of the trichloromethyl radical adduct of PBN was of similar intensity in both groups. The ethanol dose also failed to induce p-nitrophenol hydroxylase activity. When PBN and CCl4 were administered to rats, liver extracts contained ESR signals resulting primarily from the trichloromethyl radical adduct of PBN, and the signals were of similar intensity in both experimental groups. Higher concentrations of the carbon dioxide anion radical adduct of PBN were detected in plasma samples from ethanol-treated rats. However, when hepatocytes from ethanol-treated and control rats were incubated with PBN and CCl4, ESR signals of the carbon dioxide adduct were of similar intensity. These data suggest that the higher concentrations of the carbon dioxide adduct in the blood of ethanol-treated rats may be explained by early CCl4-induced damage to liver cell membranes, rather than increased rates of formation. The data in this report fail to support the hypothesis that a single dose of ethanol stimulates the hepatic metabolism of CCl4 to the trichloromethyl radical. Alternatively, ethanol may potentiate CCl4 toxicity by affecting some critical metabolic step subsequent to trichloromethyl radical formation.

  1. Comparison of ethanol toxicity to Daphnia magna and Ceriodaphnia dubia tested at two different temperatures: static acute toxicity test results

    SciTech Connect

    Takahashi, I.T.; Cowgill, U.M.; Murphy, P.G.

    1987-08-01

    Ethanol is a commonly used solvent in toxicity testing, yet there are few studies in the literature devoted to its toxicity to zooplankton. The purpose of this study was to compare the response of Daphnia magna Straus 1820 and Ceriodaphnia dubia J. Richard 1894 to ethanol. Two temperatures were selected because most toxicity data involving D. magna has been carried out at 20/sup 0/C while all discussions concerning C. dubia appear to relate to temperatures oscillating around 25/sup 0/C. Thus, the response of these two organisms to ethanol was examined at 20/sup 0/C and at 24/sup 0/C.r

  2. Acute effects of a herb extract formulation and inulin fibre on appetite, energy intake and food choice.

    PubMed

    Harrold, J A; Hughes, G M; O'Shiel, K; Quinn, E; Boyland, E J; Williams, N J; Halford, J C G

    2013-03-01

    The impact of two commercially available products, a patented herb extract Yerbe Maté, Guarana and Damiana (YGD) formulation and an inulin-based soluble fermentable fibre (SFF), alone or in combination, on appetite and food intake were studied for the first time in a double blind, placebo-controlled, cross-over design. 58 normal to slightly overweight women consumed a fixed-load breakfast followed 4h later by an ad libitum lunch. They were administered YGD (3 tablets) and SFF (5g in 100ml water), YGD and water (100ml), SFF and placebo (3 tablets) or water and placebo 15min before meals. Appetite was assessed using visual analogue scales, and energy intake was measured at lunch. Significant reductions in food intake and energy intake were observed when YGD was present (59.5g, 16.3%; 112.4kcal, 17.3%) and when SFF was present (31.9g, 9.1%; 80kcal, 11.7%) compared with conditions were products were absent. The lowest intake (gram and kcal) was in the YGD+SFF condition. Significant reductions in AUC hunger and AUC desire to eat were also observed after YGD+SFF combination. The data demonstrate that YGD produces a robust short-term effect on caloric intake, an effect augmented by SFF. Caloric compensation for SFF indicates independent effects on appetite regulation. PMID:23207186

  3. Minocycline reduces ethanol drinking.

    PubMed

    Agrawal, R G; Hewetson, A; George, C M; Syapin, P J; Bergeson, S E

    2011-06-01

    Alcoholism is a disease characterized by continued alcohol consumption despite recurring negative consequences. Thus, medications that reduce the drive to consume alcohol can be beneficial in treating alcoholism. The neurobiological systems that regulate alcohol consumption are complex and not fully understood. Currently, medications are available to treat alcoholism that act either by causing accumulation of a toxic metabolite of ethanol, or by targeting specific transmitter receptors. The purpose of our study was to investigate a new potential therapeutic pathway, neuroimmune interactions, for effects on ethanol consumption. We hypothesized that neuroimmune activity of brain glia may have a role in drinking. We utilized minocycline, a second generation tetracycline antibiotic that has immune modulatory actions, to test our hypothesis because it is known to suppress microglia, and to a lesser extent astroglia, activity following many types of insults to the brain. Treatment with 50mg/kg minocycline significantly reduced ethanol intake in male and female C57Bl/6J mice using a free choice voluntary drinking model. Saline injections did not alter ethanol intake. Minocycline had little effect on water intake or body weight change. The underlying mechanism whereby minocycline reduced ethanol intake requires further study. The results suggest that drugs that alter neuroimmune pathways may represent a new approach to developing additional therapies to treat alcoholism. PMID:21397005

  4. Opposite effects of acute ethanol exposure on GAP-43 and BDNF expression in the hippocampus versus the cerebellum of juvenile rats

    PubMed Central

    Kulkarny, V.V.; Wiest, N. E; Marquez, C.P.; Nixon, S. C.; Valenzuela, C.F.; Perrone-Bizzozero, N.I.

    2011-01-01

    The adolescent brain is particularly vulnerable to the effects of alcohol, with intoxications at this developmental age often producing long-lasting effects. The present study addresses the effects of a single acute ethanol exposure on GAP-43 and BDNF gene expression in neurons in the cerebellum and hippocampus of adolescent rats. Male postnatal day 23 (P23) Sprague-Dawley rats were exposed to ethanol vapors for two hours and after a recovery period of two hours, the cerebellum and hippocampus were harvested and samples were taken for blood alcohol concentration (BAC) determinations. We found that this exposure resulted in a mean BAC of 174 mg/dl, which resembles levels in human adolescents after binge drinking. Analyses of total RNA and protein by qRT-PCR and western blotting, respectively, revealed that this single ethanol exposure significantly decreased the levels of GAP-43 mRNA and protein in the cerebellum but increased the levels of mRNA and protein in the hippocampus. BDNF mRNA and protein levels were also increased in the hippocampus but not in the cerebellum of these animals. In situ hybridizations revealed that GAP-43 and BDNF mRNA levels were primarily increased by alcohol exposure in hippocampal dentate granule cells and CA3 neurons. Overall, the reported alterations in the expression of the plasticity-associated genes GAP-43 and BDNF in juvenile rats are consistent with the known deleterious effects of binge drinking on motor coordination and cognitive function. PMID:21367572

  5. Acute Toxicity and Gastroprotective Role of M. pruriens in Ethanol-Induced Gastric Mucosal Injuries in Rats

    PubMed Central

    Hassandarvish, Pouya; Abdul Majid, Nazia; Hadi, A. Hamid A.; Nordin, Noraziah; Abdulla, Mahmood A.

    2013-01-01

    The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg) and the experimental groups (62.5, 125, 250, and 500 mg/kg). After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions. PMID:23781513

  6. Acute toxicity and gastroprotective role of M. pruriens in ethanol-induced gastric mucosal injuries in rats.

    PubMed

    Golbabapour, Shahram; Hajrezaie, Maryam; Hassandarvish, Pouya; Abdul Majid, Nazia; Hadi, A Hamid A; Nordin, Noraziah; Abdulla, Mahmood A

    2013-01-01

    The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg) and the experimental groups (62.5, 125, 250, and 500 mg/kg). After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions. PMID:23781513

  7. The acute effects of ethanol on acetanilide disposition in normal subjects, and in patients with liver disease.

    PubMed Central

    McKay, J; Rawlings, M D; Cobden, I; James, O F

    1982-01-01

    1 The effects of single doses (25 g and 50 g) oral ethanol on the disposition of acetanilide (50 mg/kg metabolic active mass) has been studied in normal subjects, and in patients with chronic non-alcoholic liver disease. 2 In normal subjects, ethanol produced a dose-dependent increase in acetanilide half-life, and a decrease in acetenilide clearance. There was a significant correlation (rs = 0.71, P less than 0.01) between the 90 min blood ethanol concentration and the reduction in acetanilide clearance. 3 In patients with liver disease, ethanol produced a similar proportional change in acetanilide half-life and clearance, but these were less consistent. Moreover, liver disease itself was associated with an increase in acetenilide half-life, and a reduction in clearance. 4 It is concluded that single oral doses of ethanol, comparable to those consumed during social drinking, may inhibit some forms of microsomal oxidation and thus have important clinical implications. PMID:7138735

  8. Mechanism of the beneficial effects of dantrolene sodium on ethanol-induced acute gastric mucosal injury in rats.

    PubMed

    Büyükokuroğlu, Mehmet Emin; Taysi, Seyithan; Polat, Fevzi; Göçer, Fatma

    2002-05-01

    In our study, we examined anti-ulcerogen and antioxidant effects of dantrolene sodium on ethanol-induced gastric lesions in rats. Dantrolene sodium was administered intraperitoneally (i.p.) in several doses, and famotidine was used at a dose of 20 mg kg (-1). It was found that pretreatment with dantrolene sodium at doses of 1, 5 and 10 mg kg(-1) significantly reduced ethanol-induced gastric damage and malondialdehyde levels, and significantly increased antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. We conclude that dantrolene sodium clearly has antioxidant properties and that the protective effect of dantrolene sodium against ethanol-induced gastric mucosal lesion, at least in part, depends upon the reduction in the lipid peroxidation and an increase in the activity of antioxidant enzymes SOD and GSH-Px. PMID:12123631

  9. Central Agonism of GPR120 Acutely Inhibits Food Intake and Food Reward and Chronically Suppresses Anxiety-Like Behavior in Mice

    PubMed Central

    Fisette, Alexandre; Fernandes, Maria F.; Hryhorczuk, Cécile; Poitout, Vincent; Alquier, Thierry; Fulton, Stephanie

    2016-01-01

    Background: GPR120 (FFAR4) is a G-protein coupled receptor implicated in the development of obesity and the antiinflammatory and insulin-sensitizing effects of omega-3 (ω-3) polyunsaturated fatty acids. Increasing central ω-3 polyunsaturated fatty acid levels has been shown to have both anorectic and anxiolytic actions. Despite the strong clinical interest in GPR120, its role in the brain is largely unknown, and thus we sought to determine the impact of central GPR120 pharmacological activation on energy balance, food reward, and anxiety-like behavior. Methods: Male C57Bl/6 mice with intracerebroventricular cannulae received a single injection (0.1 or 1 µM) or continuous 2-week infusion (1 µM/d; mini-pump) of a GPR120 agonist or vehicle. Free-feeding intake, operant lever-pressing for palatable food, energy expenditure (indirect calorimetry), and body weight were measured. GPR120 mRNA expression was measured in pertinent brain areas. Anxiety-like behavior was assessed in the elevated-plus maze and open field test. Results: GPR120 agonist injections substantially reduced chow intake during 4 hours postinjection, suppressed the rewarding effects of high-fat/-sugar food, and blunted approach-avoidance behavior in the open field. Conversely, prolonged central GPR120 agonist infusions reduced anxiety-like behavior in the elevated-plus maze and open field, yet failed to affect free-feeding intake, energy expenditure, and body weight on a high-fat diet. Conclusion: Acute reductions in food intake and food reward suggest that GPR120 could mediate the effects of central ω-3 polyunsaturated fatty acids to inhibit appetite. The anxiolytic effect elicited by GPR120 agonist infusions favors the testing of compounds that can enter the brain to activate GPR120 for the mitigation of anxiety. PMID:26888796

  10. Effects of acute ethanol or amphetamine administration on the acoustic startle response and prepulse inhibition in adolescent and adult rats

    PubMed Central

    Brunell, Steven Craig

    2007-01-01

    Rationale Adolescents differ from adults in their sensitivity to a variety of psychoactive drugs. For example, adolescent rats are less sensitive to locomotor stimulant and stereotypic effects of amphetamine as well as to motor-impairing and hypnotic effects of ethanol while more sensitive to ethanol-induced disruption of brain plasticity. Objective The current study further explored age differences in psychopharmacological sersitivity by examining the effects of d-amphetamine (1.0 and 4.0 mg/kg) or ethanol (0.5, 1.0 and 1.5 g/kg) given interperitoneally on the acoustic startle reposnse (ASR) and prepulse inhibition (PPI) in male adolescent and adult Sprague-Dawley rats. Materials and methods The animals were given five startle trials (120 dB for 40 ms) before semi-randomized presentation of 12 startle trials interspersed with ten trials at each prepulse intensity (40 ms pulse of 5, 10, or 20 dB above background; 100 ms before the startle stimulus). Results Adolescent controls showed significantly less PPI than adults, replicating previous ontogenetic findings. The higher dose of amphetamine disrupted PPI in adult but not in adolescent insensitivity to amphetamine to include this measure of sensorimotor gating. Ethanol exposure failed to alter PPI at either age, although both the 1.0 and 1.5 g/kg doses of ethanol significantly suppressed the magnitude of the ASR at both ages, potentially reflecting sedative or anxiolytic effects. Conclusion These data provide further evidence of the relative insensitivity of adolescent animals to amphetamine, although no age effects were found in terms of ethanol sensitivity using these measures of startle and sensorimotor gating. PMID:16758242

  11. Acute effect of alginate-based preload on satiety feelings, energy intake, and gastric emptying rate in healthy subjects.

    PubMed

    Georg Jensen, Morten; Kristensen, Mette; Belza, Anita; Knudsen, Jes C; Astrup, Arne

    2012-09-01

    Viscous dietary fibers such as sodium alginate extracted from brown seaweed have received much attention lately for their potential role in energy regulation through the inhibition of energy intake and increase of satiety feelings. The aim of our study was to investigate the effect on postprandial satiety feelings, energy intake, and gastric emptying rate (GER), by the paracetamol method, of two different volumes of an alginate-based preload in normal-weight subjects. In a four-way placebo-controlled, double-blind, crossover trial, 20 subjects (age: 25.9 ± 3.4 years; BMI: 23.5 ± 1.7 kg/m(2)) were randomly assigned to receive a 3% preload concentration of either low volume (LV; 9.9 g alginate in 330 ml) or high volume (HV; 15.0 g alginate in 500 ml) alginate-based beverage, or an iso-volume placebo beverage. The preloads were ingested 30 min before a fixed breakfast and again before an ad libitum lunch. Consumption of LV-alginate preload induced a significantly lower (8.0%) energy intake than the placebo beverage (P = 0.040) at the following lunch meal, without differences in satiety feelings or paracetamol concentrations. The HV alginate significantly increased satiety feelings (P = 0.038), reduced hunger (P = 0.042) and the feeling of prospective food consumption (P = 0.027), and reduced area under the curve (iAUC) paracetamol concentrations compared to the placebo (P = 0.05). However, only a 5.5% reduction in energy intake was observed for HV alginate (P = 0.20). Although they are somewhat contradictory, our results suggest that alginate consumption does affect satiety feelings and energy intake. However, further investigation on the volume of alginate administered is needed before inferring that this fiber has a possible role in short-term energy regulation. PMID:21779093

  12. Acute effects of active gaming on ad libitum energy intake and appetite sensations of 8-11-year-old boys.

    PubMed

    Allsop, Susan; Dodd-Reynolds, Caroline J; Green, Benjamin P; Debuse, Dorothée; Rumbold, Penny L S

    2015-12-28

    The present study examined the acute effects of active gaming on energy intake (EI) and appetite responses in 8-11-year-old boys in a school-based setting. Using a randomised cross-over design, twenty-one boys completed four individual 90-min gaming bouts, each separated by 1 week. The gaming bouts were (1) seated gaming, no food or drink; (2) active gaming, no food or drink; (3) seated gaming with food and drink offered ad libitum; and (4) active gaming with food and drink offered ad libitum. In the two gaming bouts during which foods and drinks were offered, EI was measured. Appetite sensations - hunger, prospective food consumption and fullness - were recorded using visual analogue scales during all gaming bouts at 30-min intervals and at two 15-min intervals post gaming. In the two bouts with food and drink, no significant differences were found in acute EI (MJ) (P=0·238). Significant differences were detected in appetite sensations for hunger, prospective food consumption and fullness between the four gaming bouts at various time points. The relative EI calculated for the two gaming bouts with food and drink (active gaming 1·42 (sem 0·28) MJ; seated gaming 2·12 (sem 0·25) MJ) was not statistically different. Acute EI in response to active gaming was no different from seated gaming, and appetite sensations were influenced by whether food was made available during the 90-min gaming bouts. PMID:26435259

  13. Antimicrobial activity, acute toxicity and cytoprotective effect of Crassocephalum vitellinum (Benth.) S. Moore extract in a rat ethanol-HCl gastric ulcer model

    PubMed Central

    2014-01-01

    Background A decoction of Crassocephallum vitellinum (Benth.) S. Moore (Asteraceae) is used in Kagera Region to treat peptic ulcers. This study seeks to evaluate an aqueous ethanol extract of aerial parts of the plant for safety and efficacy. Methods An 80% ethanolic extract of C. vitellinum at doses of 100, 200, 400 and 800 mg/kg body wt was evaluated for ability to protect Sprague Dawley rats from acidified ethanol gastric ulceration in comparison with 40 mg/kg body wt pantoprazole. The extract and its dichloromethane, ethyl acetate, and aqueous fractions were also evaluated for acute toxicity in mice, brine shrimp toxicity, and antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholera (clinical isolate), and Streptococcus faecalis (clinical isolate). The groups of phytochemicals present in the extract were also determined. Results The ethanolic extract of C. vitellinum dose-dependently protected rat gastric mucosa against ethanol/HCl insult to a maximum of 88.3% at 800 mg/kg body wt, affording the same level of protection as by 40 mg/kg body wt pantoprazole. The extract also exhibited weak antibacterial activity against S. typhi and E. coli, while its ethyl acetate, dichloromethane and aqueous fractions showed weak activity against K. pneumonia, S.typhi, E. coli and V. cholera. The extract was non-toxic to mice up to 5000 mg/kg body wt, and the total extract (LC50 = 37.49 μg/ml) and the aqueous (LC50 = 87.92 μg/ml), ethyl acetate (LC50 = 119.45 μg/ml) and dichloromethane fractions (88.79 μg/ml) showed low toxicity against brine shrimps. Phytochemical screening showed that the extract contains tannins, saponins, flavonoids, and terpenoids. Conclusion The results support the claims by traditional healers that a decoction of C.vitellinum has antiulcer activity. The mechanism of cytoprotection is yet to be determined but the phenolic compounds present in the

  14. Juvenile ethanol exposure increases rewarding properties of cocaine and morphine in adult DBA/2J mice.

    PubMed

    Molet, Jenny; Hervé, Denis; Thiébot, Marie-Hélène; Hamon, Michel; Lanfumey, Laurence

    2013-12-01

    Convergent data showed that ethanol exposure during adolescence can alter durably ethanol-related behaviour at adulthood. However, the consequences of juvenile ethanol exposure on the reinforcing effects of other drugs of abuse remain unclear. In the present work, we evaluated in adult male DBA/2J mice the effects of early ethanol exposure on the sensitivity to the incentive effects of cocaine and morphine, and on extracellular signal-regulated kinase (ERK) activation in response to cocaine. Juvenile male mice received intragastric administration of ethanol (2×2.5g/kg/day) or water for 5 days starting on postnatal day 28. When reaching adult age (10 week-old), animals were subjected to an unbiased procedure to assess conditioned place preference (CPP) to cocaine or morphine. In addition, activation of ERK in response to an acute injection of cocaine was investigated using immunoblotting in the striatum and the nucleus accumbens. Mice that have been subjected to early ethanol exposure developed CPP to doses of cocaine (5mg/kg) or morphine (10mg/kg) below the threshold doses to induce CPP in water pre-exposed mice. In addition, early ethanol administration significantly increased striatal ERK phosphorylation normally induced by acute cocaine (10 and 20mg/kg) in adult mice. These results show that, in DBA/2J mice, early exposure to ethanol enhanced the perception of the incentive effects of cocaine and morphine. Ethanol pre-exposure also induced a positive modulation of striatal ERK signalling, in line with the inference that juvenile ethanol intake may contribute to the development of addictive behaviour at adult age. PMID:23619165

  15. Anti-ulcerogenic effect of cavidine against ethanol-induced acute gastric ulcer in mice and possible underlying mechanism.

    PubMed

    Li, Weifeng; Wang, Xiumei; Zhang, Hailin; He, Zehong; Zhi, Wenbing; Liu, Fang; Wang, Yu; Niu, Xiaofeng

    2016-09-01

    Cavidine, a major alkaloid compound isolated from Corydalis impatiens, has various pharmacological effects but its effect on gastric ulcer has not been previously explored. The current study aimed to investigate the possible anti-ulcerogenic potential of cavidine in the model of ethanol-induced gastric ulcer. Mice received cavidine (1, 5 or 10mg/kg, ig), cimetidine (CMD, 100mg/kg, ig) or vehicle at 12h and 1h before absolute ethanol administration (0.5mL/100g), and animals were euthanized 3h after ethanol ingestion. Gross and histological gastric lesions, biochemical, immunological and Western blot parameters were taken into consideration. The results showed that ethanol administration produced apparent mucosal injuries with morphological and histological damage, whereas cavidine pre-treatment reduced the gastric injuries. Cavidine pre-treatment also ameliorated the contents of malonaldehyde (MDA) and myeloperoxidase (MPO) activity, and increased the mucosa levels of glutathione (GSH), superoxide dismutase (SOD) and prostaglandin E2 (PGE2), relative to the model group. Also cavidine was able to decrease the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), inhibit the up-regulation of cyclo-oxygenase-2 (COX-2) expression and activation of Nuclear factor-kappa B (NF-κB) pathway. Taken together, these results indicated that cavidine exerts a gastroprotective effect against gastric ulceration, and the underlying mechanism might be associated with the stimulation of PGE2, reduction of oxidative stress, suppression of NF-κB expression and subsequent reduced COX-2 and pro-inflammatory cytokines. PMID:27380619

  16. Gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves against acute gastric lesion models in rodents.

    PubMed

    Fernandes, Hélio B; Silva, Francilene V; Passos, Flávia Franceli B; Bezerra, Roosevelt D S; Chaves, Mariana H; Oliveira, Francisco A; Oliveira, Rita C Meneses

    2010-01-01

    Parkia platycephala Benth. (Leguminosae--Mimosoideae), popularly known as "visgueira", fava bean tree or "fava-de-bolota", is widely found in the Northern and Northeastern regions of Brazil. Its pods are used as cattle food supplement in the drought period. Compounds with a gastroprotective activity were obtained from the genus Parkia. Therefore, this study aimed at investigating the gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves (Pp-EtOH), as well as evaluating its possible mechanisms of action in experimental ulcer induction models. Lesions were induced by absolute ethanol, ethanol-HCl, ischemia-reperfusion and indomethacin in rodents. Pp-EtOH showed a protective effect in the lesion models (66, 48 and 52%, respectively), but it was not able to protect gastric mucosa against indomethacin-induced lesions. Results show a possible participation of the NO-synthase pathway in the gastroprotection and an antioxidant activity, by the increase of the catalase activity. The participation of prostaglandins and potassium channels sensitive to ATP in the gastroprotective effect of Pp-EtOH seems less likely to occur. More comprehensive studies, therefore, should be carried out to elucidate the antiulcerative effects of this promising natural product against this gastrointestinal disorder. PMID:21526272

  17. Gene expression changes in mononuclear cells in patients with metabolic syndrome after acute intake of phenol-rich virgin olive oil

    PubMed Central

    2010-01-01

    Background Previous studies have shown that acute intake of high-phenol virgin olive oil reduces pro-inflammatory, pro-oxidant and pro-thrombotic markers compared with low phenols virgin olive oil, but it still remains unclear whether effects attributed to its phenolic fraction are exerted at transcriptional level in vivo. To achieve this goal, we aimed at identifying expression changes in genes which could be mediated by virgin olive oil phenol compounds in the human. Results Postprandial gene expression microarray analysis was performed on peripheral blood mononuclear cells during postprandial period. Two virgin olive oil-based breakfasts with high (398 ppm) and low (70 ppm) content of phenolic compounds were administered to 20 patients suffering from metabolic syndrome following a double-blinded, randomized, crossover design. To eliminate the potential effect that might exist in their usual dietary habits, all subjects followed a similar low-fat, carbohydrate rich diet during the study period. Microarray analysis identified 98 differentially expressed genes (79 underexpressed and 19 overexpressed) when comparing the intake of phenol-rich olive oil with low-phenol olive oil. Many of these genes seem linked to obesity, dyslipemia and type 2 diabetes mellitus. Among these, several genes seem involved in inflammatory processes mediated by transcription factor NF-κB, activator protein-1 transcription factor complex AP-1, cytokines, mitogen-activated protein kinases MAPKs or arachidonic acid pathways. Conclusion This study shows that intake of virgin olive oil based breakfast, which is rich in phenol compounds is able to repress in vivo expression of several pro-inflammatory genes, thereby switching activity of peripheral blood mononuclear cells to a less deleterious inflammatory profile. These results provide at least a partial molecular basis for reduced risk of cardiovascular disease observed in Mediterranean countries, where virgin olive oil represents a main

  18. The influence of time in captivity, food intake and acute trauma on blood analytes of juvenile Steller sea lions, Eumetopias jubatus.

    PubMed

    Skinner, John P; Tuomi, Pam A; Mellish, Jo-Ann E

    2015-01-01

    The Steller sea lion, Eumetopias jubatus, has experienced regionally divergent population trends over recent decades. One potential mechanism for this disparity is that local factors cause reduced health and, therefore, reduced survival of individuals. The use of blood parameters to assess sea lion health may help to identify whether malnutrition, disease and stress are important drivers of current trends, but such assessments require species-specific knowledge of how parameters respond to various health challenges. We used principal components analysis to identify which key blood parameters (principal analytes) best described changes in health for temporarily captive juvenile Steller sea lions in known conditions. Generalized additive mixed models were used to estimate the changes in principal analytes with food intake, time in captivity and acute trauma associated with hot-iron branding and transmitter implant surgery. Of the 17 blood parameters examined, physiological changes for juvenile sea lions were best described using the following six principal analytes: red blood cell counts, white blood cell counts, globulin, platelets, glucose and total bilirubin. The white blood cell counts and total bilirubin declined over time in captivity, whereas globulin increased. Elevated red blood cell counts, white blood cell counts and total bilirubin and reduced globulin values were associated with lower food intake. After branding, white blood cell counts were elevated for the first 30 days, while globulin and platelets were elevated for the first 15 days only. After implant surgery, red blood cell counts and globulin remained elevated for 30 days, while white blood cell counts remained elevated during the first 15 days only. Glucose was unassociated with the factors we studied. These results were used to provide expected ranges for principal analytes at different levels of food intake and in response to the physical challenges of branding and implant surgery

  19. The influence of time in captivity, food intake and acute trauma on blood analytes of juvenile Steller sea lions, Eumetopias jubatus

    PubMed Central

    Skinner, John P.; Tuomi, Pam A.; Mellish, Jo-Ann E.

    2015-01-01

    The Steller sea lion, Eumetopias jubatus, has experienced regionally divergent population trends over recent decades. One potential mechanism for this disparity is that local factors cause reduced health and, therefore, reduced survival of individuals. The use of blood parameters to assess sea lion health may help to identify whether malnutrition, disease and stress are important drivers of current trends, but such assessments require species-specific knowledge of how parameters respond to various health challenges. We used principal components analysis to identify which key blood parameters (principal analytes) best described changes in health for temporarily captive juvenile Steller sea lions in known conditions. Generalized additive mixed models were used to estimate the changes in principal analytes with food intake, time in captivity and acute trauma associated with hot-iron branding and transmitter implant surgery. Of the 17 blood parameters examined, physiological changes for juvenile sea lions were best described using the following six principal analytes: red blood cell counts, white blood cell counts, globulin, platelets, glucose and total bilirubin. The white blood cell counts and total bilirubin declined over time in captivity, whereas globulin increased. Elevated red blood cell counts, white blood cell counts and total bilirubin and reduced globulin values were associated with lower food intake. After branding, white blood cell counts were elevated for the first 30 days, while globulin and platelets were elevated for the first 15 days only. After implant surgery, red blood cell counts and globulin remained elevated for 30 days, while white blood cell counts remained elevated during the first 15 days only. Glucose was unassociated with the factors we studied. These results were used to provide expected ranges for principal analytes at different levels of food intake and in response to the physical challenges of branding and implant surgery

  20. Post-Intake of S-Ethyl Cysteine and S-Methyl Cysteine Improved LPS-Induced Acute Lung Injury in Mice.

    PubMed

    Hsia, Te-Chun; Yin, Mei-Chin

    2016-01-01

    The effects of S-ethyl cysteine (SEC) and S-methyl cysteine (SMC) on lipopolysaccharide (LPS)-induced acute lung injury in mice were examined. Eight hours after LPS challenge, SEC or SMC was supplied in drinking water at 0.5% or 1% for 3 days. LPS increased lung myeloperoxidase activity, neutrophil counts and edema. SEC or SMC post-intake attenuated these events. SEC or SMC suppressed LPS-induced lung expression of cyclooxygenase-2, nuclear factor-κB and mitogen-activated protein kinase, and lowered the generation of tumor necrosis factor-alpha, monocyte chemoattractant protein-1 and prostaglandin E₂. LPS enhanced the expression of p47(phox), gp91(phox), Bax and cleaved caspase-3, and increased the production of reactive oxygen species in the lung. SEC or SMC post-intake reversed these alterations. These findings suggest that these agents could protect the lung through their anti-inflammatory, anti-oxidative and anti-apoptotic activities. PMID:27548215

  1. Post-Intake of S-Ethyl Cysteine and S-Methyl Cysteine Improved LPS-Induced Acute Lung Injury in Mice

    PubMed Central

    Hsia, Te-chun; Yin, Mei-chin

    2016-01-01

    The effects of S-ethyl cysteine (SEC) and S-methyl cysteine (SMC) on lipopolysaccharide (LPS)-induced acute lung injury in mice were examined. Eight hours after LPS challenge, SEC or SMC was supplied in drinking water at 0.5% or 1% for 3 days. LPS increased lung myeloperoxidase activity, neutrophil counts and edema. SEC or SMC post-intake attenuated these events. SEC or SMC suppressed LPS-induced lung expression of cyclooxygenase-2, nuclear factor-κB and mitogen-activated protein kinase, and lowered the generation of tumor necrosis factor-alpha, monocyte chemoattractant protein-1 and prostaglandin E2. LPS enhanced the expression of p47phox, gp91phox, Bax and cleaved caspase-3, and increased the production of reactive oxygen species in the lung. SEC or SMC post-intake reversed these alterations. These findings suggest that these agents could protect the lung through their anti-inflammatory, anti-oxidative and anti-apoptotic activities. PMID:27548215

  2. A study of antimicrobial activity, acute toxicity and cytoprotective effect of a polyherbal extract in a rat ethanol-HCl gastric ulcer model

    PubMed Central

    2012-01-01

    Background The decoction of the aerial parts of Rhynchosia recinosa (A.Rich.) Bak. [Fabaceae] is used in combination with the stem barks of Ozoroa insignis Del. (Anacardiaceae), Maytenus senegalensis (Lam.) Excell. [Celastraceae] Entada abyssinica Steud. ex A.Rich [Fabaceae] and Lannea schimperi (Hochst.)Engl. [Anacardiaceae] as a traditional remedy for managing peptic ulcers. However, the safety and efficacy of this polyherbal preparation has not been evaluated. This study reports on the phytochemical profile and some biological activities of the individual plant extracts and a combination of extracts of the five plants. Methods A mixture of 80% ethanol extracts of R. recinosa, O. insignis, M. senegalensis, E. abyssinica and L. schimperi at doses of 100, 200, 400 and 800 mg/kg body wt were evaluated for ability to protect Sprague Dawley rats from gastric ulceration by an ethanol-HCl mixture. Cytoprotective effect was assessed by comparison with a negative control group given 1% tween 80 in normal saline and a positive control group given 40 mg/kg body wt pantoprazole. The individual extracts and their combinations were also tested for antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholerae (clinical isolate), and Klebsiella pneumoniae (clinical isolate) using the microdilution method. In addition the extracts were evaluated for brine shrimp toxicity and acute toxicity in mice. Phytochemical tests were done using standard methods to determine the presence of tannins, saponins, steroids, cardiac glycosides, flavonoids, alkaloids and terpenoids in the individual plant extracts and in the mixed extract of the five plants. Results The combined ethanolic extracts of the 5 plants caused a dose-dependent protection against ethanol/HCl induced ulceration of rat gastric mucosa, reaching 81.7% mean protection as compared to 87.5% protection by 40 mg/kg body wt pantoprazole. Both the individual

  3. Changes in brain regions associated with food-intake regulation, body mass and metabolic profiles during acute antipsychotic treatment in first-episode schizophrenia.

    PubMed

    Emsley, Robin; Asmal, Laila; Chiliza, Bonginkosi; du Plessis, Stefan; Carr, Jonathan; Kidd, Martin; Malhotra, Anil K; Vink, Matthijs; Kahn, Rene S

    2015-08-30

    We investigated whether morphological brain changes occurred in brain regions associated with body-weight homeostasis during acute antipsychotic treatment, and if so, whether they were related to changes in body mass and metabolic profile. Twenty-two antipsychotic-naive patients with first-episode schizophrenia received either risperidone long acting injection or flupenthixol decanoate over 13 weeks and were compared by structural MRI with 23 matched healthy volunteers at weeks 0, 4 and 13. Images were reconstructed using freesurfer fully-automated whole brain segmentation. The ventral diencephalon and prefrontal cortex were selected to represent the homeostatic and hedonic food intake regulatory systems respectively. Body mass was measured at weeks 0, 7 and 13 and fasting glucose and lipid profiles at weeks 0 and 13. Linear mixed effect models indicated significant group(⁎)time interactions for the ventral diencephalon volumes bilaterally. Ventral diencephalon volume reduction was strongly correlated bilaterally with body mass increase and HDL-cholesterol reductions, and unilaterally with blood glucose elevation. There were no significant changes in prefrontal cortical thickness. These findings implicate the ventral diencephalon, of which the hypothalamus is the main component, in the acute adipogenic and dyslipidaemic effects of antipsychotic medication. PMID:26184461

  4. Acute effects of ethanol or d-amphetamine on the locomotor activity of larval zebrafish in a microtiter plate format.

    EPA Science Inventory

    As part of an effort to develop a rapid in vivo screen for EPA’s prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae. We are assessing the acute effects of prototypic drugs that are known to act on the central ...

  5. Exercise of low energy expenditure along with mild energy intake restriction acutely reduces fasting and postprandial triacylglycerolaemia in young women.

    PubMed

    Maraki, Maria; Christodoulou, Nektarios; Aggelopoulou, Niki; Magkos, Faidon; Skenderi, Katerina P; Panagiotakos, Demosthenes; Kavouras, Stavros A; Sidossis, Labros S

    2009-02-01

    A single bout of prolonged, moderate-intensity endurance exercise lowers fasting and postprandial TAG concentrations the next day. However, the TAG-lowering effect of exercise is dose-dependent and does not manifest after light exercise of low energy cost ( < 2 MJ). We aimed to investigate whether superimposing mild energy intake restriction to such exercise, in order to augment total energy deficit, potentiates the hypotriacylglycerolaemic effect. Eight healthy, sedentary, premenopausal women (age 27.1 (sem 1.3) years; BMI 21.8 (sem 0.9) kg/m2) performed two oral fat tolerance tests in the morning on two different occasions: once after a single bout of light exercise (100 min at 30 % of peak oxygen consumption; net energy expenditure 1.04 (sem 0.01) MJ) coupled with mild energy intake restriction (1.39 (sem 0.22) MJ) on the preceding day, and once after resting coupled with isoenergetic feeding on the preceding day (control). Fasting plasma TAG, TAG in the TAG-rich lipoproteins (TRL-TAG) and serum insulin concentrations were 18, 34 and 30 % lower, respectively, after exercise plus diet compared with the control trial (P < 0.05). Postprandial concentrations of plasma TAG and TRL-TAG were 19 and 27 % lower after exercise plus diet compared with the control condition (P < 0.01), whereas postprandial insulin concentrations were not different. It is concluded that a combination of light exercise along with mild hypoenergetic diet may be a practical and feasible intervention to attenuate fasting and postprandial triacylglycerolaemia, especially for people who cannot exercise for prolonged periods of time at moderate-to-high intensities, such as many sedentary individuals. PMID:18570693

  6. Cinnamon intake alleviates the combined effects of dietary-induced insulin resistance and acute stress on brain mitochondria.

    PubMed

    Couturier, Karine; Hininger, Isabelle; Poulet, Laurent; Anderson, Richard A; Roussel, Anne-Marie; Canini, Frédéric; Batandier, Cécile

    2016-02-01

    Insulin resistance (IR), which is a leading cause of the metabolic syndrome, results in early brain function alterations which may alter brain mitochondrial functioning. Previously, we demonstrated that rats fed a control diet and submitted to an acute restraint stress exhibited a delayed mitochondrial permeability transition pore (mPTP) opening. In this study, we evaluated the combined effects of dietary and emotional stressors as found in western way of life. We studied, in rats submitted or not to an acute stress, the effects of diet-induced IR on brain mitochondria, using a high fat/high fructose diet (HF(2)), as an IR inducer, with addition or not of cinnamon as an insulin sensitizer. We measured Ca(2+) retention capacity, respiration, ROS production, enzymatic activities and cell signaling activation. Under stress, HF(2) diet dramatically decreased the amount of Ca(2+) required to open the mPTP (13%) suggesting an adverse effect on mitochondrial survival. Cinnamon added to the diet corrected this negative effect and resulted in a partial recovery (30%). The effects related to cinnamon addition to the diet could be due to its antioxidant properties or to the observed modulation of PI3K-AKT-GSK3β and MAPK-P38 pathways or to a combination of both. These data suggest a protective effect of cinnamon on brain mitochondria against the negative impact of an HF(2) diet. Cinnamon could be beneficial to counteract deleterious dietary effects in stressed conditions. PMID:26878796

  7. Calorie intake and patient outcomes in severe acute kidney injury: findings from The Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study trial

    PubMed Central

    2014-01-01

    Introduction Current practice in the delivery of caloric intake (DCI) in patients with severe acute kidney injury (AKI) receiving renal replacement therapy (RRT) is unknown. We aimed to describe calorie administration in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study and to assess the association between DCI and clinical outcomes. Methods We performed a secondary analysis in 1456 patients from the RENAL trial. We measured the dose and evolution of DCI during treatment and analyzed its association with major clinical outcomes using multivariable logistic regression, Cox proportional hazards models, and time adjusted models. Results Overall, mean DCI during treatment in ICU was low at only 10.9 ± 9 Kcal/kg/day for non-survivors and 11 ± 9 Kcal/kg/day for survivors. Among patients with a lower DCI (below the median) 334 of 729 (45.8%) had died at 90-days after randomization compared with 316 of 727 (43.3%) patients with a higher DCI (above the median) (P = 0.34). On multivariable logistic regression analysis, mean DCI carried an odds ratio of 0.95 (95% confidence interval (CI): 0.91-1.00; P = 0.06) per 100 Kcal increase for 90-day mortality. DCI was not associated with significant differences in renal replacement (RRT) free days, mechanical ventilation free days, ICU free days and hospital free days. These findings remained essentially unaltered after time adjusted analysis and Cox proportional hazards modeling. Conclusions In the RENAL study, mean DCI was low. Within the limits of such low caloric intake, greater DCI was not associated with improved clinical outcomes. Trial registration ClinicalTrials.gov number, NCT00221013 PMID:24629036

  8. Intake port

    DOEpatents

    Mendler, Edward Charles

    2005-02-01

    The volumetric efficiency and power of internal combustion engines is improved with an intake port having an intake nozzle, a venturi, and a surge chamber. The venturi is located almost halfway upstream the intake port between the intake valves and the intake plenum enabling the venturi throat diameter to be exceptionally small for providing an exceptionally high ram velocity and an exceptionally long and in turn high efficiency diffuser flowing into the surge chamber. The intake port includes an exceptionally large surge chamber volume for blow down of the intake air into the working cylinder of the engine.

  9. Acute Sodium Arsenite-Induced Hematological and Biochemical Changes in Wistar Rats: Protective Effects of Ethanol Extract of Ageratum conyzoides

    PubMed Central

    Ola-Davies, Olufunke Eunice; Akinrinde, Akinleye Stephen

    2016-01-01

    Background: Ageratum conyzoides L. (Asteraceae) is an annual herbaceous plant used in folklore medicine for the treatment of a wide range of diseases. Objective: To investigate the protective effect of the ethanol leaf extract of A. conyzoides (EEAC) against hematological, serum biochemical and histological alterations induced by Sodium arsenite administration to Wistar rats. Materials and Methods: Twenty male Wistar rats were randomly assigned into four groups of five rats each. Group I received propylene glycol and Group II rats were given the (EEAC, 100 mg/kg b.w.) orally for 7 days. Group III were given a single oral dose of sodium arsenite (NaAsO2, 2.5 mg/kg b.w.). Animals in Group IV were pretreated with 100 mg/kg EEAC for 7 days followed by a single oral dose of sodium arsenite. Results: Arsenic exposure resulted in significant reductions (P < 0.05) in values of packed cell volume (PCV), hemoglobin concentration (Hb) and red blood cell (RBC) count, and elevation in total white blood cell (WBC) count with insignificant reductions in serum total protein, albumin, and globulin levels. Alterations in aspartate aminotransferase, alanine transferase, alkaline phosphatase, and gamma glutamyl transferase activities, as well as in serum levels of urea, creatinine, glucose, cholesterol, and triglyceride levels, were not statistically significant. EEAC significantly restored (P < 0.05) the PCV, Hb, RBC, and WBC as well as serum albumin, globulin, and total protein to normal values. Conclusion: The results of this study indicate that EEAC possess strong potentials to protect against toxicities induced by sodium arsenite. SUMMARY Ageratum conyzoides produced significant reversal of the reduction in the erythrocytic indices (packed cell volume, red blood cell, and Hb) caused by sodium arseniteSodium arsenite-induced slight elevations in serum aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), correlating with the

  10. The Orphan G Protein-Coupled Receptor Gene GPR178 Is Evolutionary Conserved and Altered in Response to Acute Changes in Food Intake

    PubMed Central

    Shirazi Fard, Shahrzad; Haitina, Tatjana; Olszewski, Pawel K.; Alsiö, Johan; Schiöth, Helgi B.; Fredriksson, Robert

    2015-01-01

    G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating physiological functions fundamental for survival, including energy homeostasis. A few years ago, an amino acid sequence of a novel GPCR gene was identified and named GPR178. In this study, we provide new insights regarding the biological significance of Gpr178 protein, investigating its evolutionary history and tissue distribution as well as examining the relationship between its expression level and feeding status. Our phylogenetic analysis indicated that GPR178 is highly conserved among all animal species investigated, and that GPR178 is not a member of a protein family. Real-time PCR and in situ hybridization revealed wide expression of Gpr178 mRNA in both the brain and periphery, with high expression density in the hypothalamus and brainstem, areas involved in the regulation of food intake. Hence, changes in receptor expression were assessed following several feeding paradigms including starvation and overfeeding. Short-term starvation (12–48h) or food restriction resulted in upregulation of Gpr178 mRNA expression in the brainstem, hypothalamus and prefrontal cortex. Conversely, short-term (48h) exposure to sucrose or Intralipid solutions downregulated Gpr178 mRNA in the brainstem; long-term exposure (10 days) to a palatable high-fat and high-sugar diet resulted in a downregulation of Gpr178 in the amygdala but not in the hypothalamus. Our results indicate that hypothalamic Gpr178 gene expression is altered during acute exposure to starvation or acute exposure to palatable food. Changes in gene expression following palatable diet consumption suggest a possible involvement of Gpr178 in the complex mechanisms of feeding reward. PMID:26047506

  11. Acute Nicotine Administration Increases BOLD fMRI Signal in Brain Regions Involved in Reward Signaling and Compulsive Drug Intake in Rats

    PubMed Central

    Alexander, Jon C.; Perez, Pablo D.; Bauzo-Rodriguez, Rayna; Hall, Gabrielle; Klausner, Rachel; Guerra, Valerie; Zeng, Huadong; Igari, Moe; Febo, Marcelo

    2015-01-01

    Background: Acute nicotine administration potentiates brain reward function and enhances motor and cognitive function. These studies investigated which brain areas are being activated by a wide range of doses of nicotine, and if this is diminished by pretreatment with the nonselective nicotinic receptor antagonist mecamylamine. Methods: Drug-induced changes in brain activity were assessed by measuring changes in the blood oxygen level dependent (BOLD) signal using an 11.1-Tesla magnetic resonance scanner. In the first experiment, nicotine naïve rats were mildly anesthetized and the effect of nicotine (0.03–0.6mg/kg) on the BOLD signal was investigated for 10min. In the second experiment, the effect of mecamylamine on nicotine-induced brain activity was investigated. Results: A high dose of nicotine increased the BOLD signal in brain areas implicated in reward signaling, such as the nucleus accumbens shell and the prelimbic area. Nicotine also induced a dose-dependent increase in the BOLD signal in the striato-thalamo-orbitofrontal circuit, which plays a role in compulsive drug intake, and in the insular cortex, which contributes to nicotine craving and relapse. In addition, nicotine induced a large increase in the BOLD signal in motor and somatosensory cortices. Mecamylamine alone did not affect the BOLD signal in most brain areas, but induced a negative BOLD response in cortical areas, including insular, motor, and somatosensory cortices. Pretreatment with mecamylamine completely blocked the nicotine-induced increase in the BOLD signal. Conclusions: These studies demonstrate that acute nicotine administration activates brain areas that play a role in reward signaling, compulsive behavior, and motor and cognitive function. PMID:25552431

  12. Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P) Rats

    PubMed Central

    Godfrey, Jessica; Jeanguenin, Lisa; Castro, Norma; Olney, Jeffrey J.; Dudley, Jason; Pipkin, Joseph; Walls, Stanley M.; Wang, Wei; Herr, Deron R.; Harris, Greg L.; Brasser, Susan M.

    2015-01-01

    Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P) rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total) or were given access only to water (control). Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4)-desaturase (Degs2), an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels achieved by

  13. Antioxidant Properties and Gastroprotective Effects of 2-(Ethylthio)Benzohydrazones on Ethanol-Induced Acute Gastric Mucosal Lesions in Rats

    PubMed Central

    Ariffin, Azhar; Abdulla, Mahmood A.; Abdullah, Zanariah

    2016-01-01

    A series of new 2-(ethylthio)benzohydrazone derivatives (1–6) were prepared and characterised by IR, 1H NMR, and 13C NMR spectroscopy and mass spectrometry. The newly prepared compounds were screened for their in vitro antioxidant activities using free radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Among them, most powerful antioxidant, compound 1 has been selected in order to illustrate anti-ulcer effect on ethanol-induced gastric mucosal lesions in rats. Four groups of Sprague Dawley rats were respectively treated with 10% Tween 20 as ulcer control group, 20 mg/kg omeprazole as reference group, 50 mg/kg and 100 mg/kg compound 1 as experimental animals. Macroscopically, ulcer control group showed extensive hemorrhagic lesions of gastric mucosa compared with omeprazole or compound 1. Rats pre-treated with compound 1 showed increased in gastric pH and gastric mucus. Histologically, ulcer control group showed severe damage to gastric mucosa with edema and leucocytes infiltration of submucosal layer. In immunohistochemical analysis, rats which were pre-treated with compound 1 showed up-regulation of HSP70 and down-regulation of Bax proteins. In conclusion, the gastroprotective effect of compound 1 may be due to its antioxidant activity, and/or due to up-regulation of HSP70 and down-regulation of Bax protein in stained tissue section. PMID:27272221

  14. Moderate ethanol ingestion and cardiovascular protection: from epidemiologic associations to cellular mechanisms.

    PubMed

    Krenz, Maike; Korthuis, Ronald J

    2012-01-01

    While ethanol intake at high levels (3-4 or more drinks), either in acute (occasional binge drinking) or chronic (daily) settings, increases the risk for myocardial infarction and stroke, an inverse relationship between regular consumption of alcoholic beverages at light to moderate levels (1-2 drinks per day) and cardiovascular risk has been consistently noted in a large number of epidemiologic studies. Although initially attributed to polyphenolic antioxidants in red wine, subsequent work has established that the ethanol component contributes to the beneficial effects associated with moderate intake of alcoholic beverages regardless of type (red versus white wine, beer, spirits). Concerns have been raised with regard to interpretation of epidemiologic evidence for this association including heterogeneity of the reference groups examined in many studies, different lifestyles of moderate drinkers versus abstainers, and favorable risk profiles in moderate drinkers. However, better controlled epidemiologic studies and especially work conducted in animal models and cell culture systems have substantiated this association and clearly established a cause and effect relationship between alcohol consumption and reductions in tissue injury induced by ischemia/reperfusion (I/R), respectively. The aims of this review are to summarize the epidemiologic evidence supporting the effectiveness of ethanol ingestion in reducing the likelihood of adverse cardiovascular events such as myocardial infarction and ischemic stroke, even in patients with co-existing risk factors, to discuss the ideal quantities, drinking patterns, and types of alcoholic beverages that confer protective effects in the cardiovascular system, and to review the findings of recent experimental studies directed at uncovering the mechanisms that underlie the cardiovascular protective effects of antecedent ethanol ingestion. Mechanistic interrogation of the signaling pathways invoked by antecedent ethanol

  15. Role of melanin-concentrating hormone in the control of ethanol consumption: Region-specific effects revealed by expression and injection studies

    PubMed Central

    Morganstern, I; Chang, G-Q; Chen, Y-W; Barson, J.R; Zhiyu, Y; Hoebel, B.G; Leibowitz, S.F

    2010-01-01

    The peptide melanin-concentrating hormone (MCH), produced mainly by cells in the lateral hypothalamus (LH), perifornical area (PF) and zona incerta (ZI), is suggested to have a role in the consumption of rewarding substances, such as ethanol, sucrose and palatable food. However, there is limited information on the specific brain sites where MCH acts to stimulate intake of these rewarding substances and on the feedback effects that their consumption has on the expression of endogenous MCH. The current study investigated MCH in relation to ethanol consumption, in Sprague-Dawley rats. In Experiment 1, chronic consumption of ethanol (from 0.70 to 2.7 g/kg/day) dose-dependently reduced MCH gene expression in the LH. In Experiments 2–4, the opposite effect was observed with acute oral ethanol, which stimulated MCH expression specifically in the LH but not the ZI. In Experiment 5, the effect of MCH injection in brain-cannulated rats on ethanol consumption was examined. Compared to saline, MCH injected in the paraventricular nucleus (PVN) and nucleus accumbens (NAc) selectively stimulated ethanol consumption without affecting food or water intake. In contrast, it reduced ethanol intake when administered into the LH, while having no effect in the ZI. These results demonstrate that voluntary, chronic consumption of ethanol leads to local negative feedback control of MCH expression in the LH. However, with a brief exposure, ethanol stimulates MCH-expressing neurons in this region, which through projections to the feeding-related PVN and reward-related NAc can promote further drinking behavior. PMID:20670637

  16. Concomitant Intake of Quercetin with a Grain-Based Diet Acutely Lowers Postprandial Plasma Glucose and Lipid Concentrations in Pigs

    PubMed Central

    Wein, Silvia; Wolffram, Siegfried

    2014-01-01

    Treatment goals of diabetes mellitus type 2 (DMT2) include glycemic control and reduction of nonglycemic risk factors, for example, dyslipidemia. Quercetin, a plant-derived polyphenol, often discussed for possible antidiabetic effects, was investigated for acute postprandial glucose- and lipid-lowering effects in healthy growing pigs. Male pigs (n = 16, body weight = BW 25–30 kg) were fed flavonoid-poor grain-based meals without (GBM) or with quercetin (GBMQ). In a first experiment, postprandial plasma concentrations of glucose, nonesterified fatty acids (NEFA), and triacylglycerols were analyzed in 8 pigs receiving 500 g of either GBM or GBMQ (10 mg/kg BW) in a cross-over design. Blood samples were collected before, and up to 5 h every 30 min, as well as 6 and 8 h after the feeding. In the second experiment, 2 h after ingestions of 1000 g of either GBM or GBMQ (50 mg/kg BW) animals were sacrificed; gastric content was collected and analyzed for dry matter content. Quercetin ingestion reduced postprandial glucose, NEFA, and TG concentration, but two hours after ingestion of the meal no effect on gastric emptying was observed. Our results point to inhibitory effects of quercetin on nutrient absorption, which appear not to be attributable to delayed gastric emptying. PMID:24847478

  17. [The protective effect of pantothenic acid derivatives and changes in the system of acetyl CoA metabolism in acute ethanol poisoning].

    PubMed

    Moiseenok, A G; Dorofeev, B F; Omel'ianchik, S N

    1988-01-01

    Calcium pantothenate (CaP), calcium 4'-phosphopantothenate (CaPP), pantethine, panthenol, sulfopantetheine and CoA decrease acute toxicity of acetaldehyde in mice. All studied compounds diminish duration of the narcotic action of ethanol--ET (3.5 g/kg intraperitoneally) in mice and rats. In the latter this effect is realized at the expense of "long sleeping" and "middle sleeping" animals. CaP (150 mg/kg subcutaneously) and CaPP (100 mg/kg subcutaneously) prevent hypothermia and a decrease of oxygen consumption in rats induced by ET administration. Combined administration of ET, CaP and CaPP leads to a characteristic increase of acid-soluble CoA fractions in the rat liver and a relative decrease of acetyl CoA synthetase and N-acetyltransferase reactions. The antitoxic effect of preparations of pantothenic acid is not mediated by CoA-dependent reactions of detoxication, but most probably is due to intensification of ET oxidation and perhaps to its elimination from the organism. PMID:2905277

  18. Ethanol Extract of Fructus Schisandrae Decreases Hepatic Triglyceride Level in Mice Fed with a High Fat/Cholesterol Diet, with Attention to Acute Toxicity

    PubMed Central

    Pan, Si-Yuan; Yu, Zhi-Ling; Dong, Hang; Xiang, Chun-Jing; Fong, Wang-Fun; Ko, Kam-Ming

    2011-01-01

    Effects of the ethanol extract of Fructus Schisandrae (EtFSC) on serum and liver lipid contents were investigated in mice fed with high fat/cholesterol (HFC) diet for 8 or 15 days. The induction of hypercholesterolemia by HFC diet caused significant increases in serum and hepatic total cholesterol (TC) levels (up to 62% and 165%, resp.) and hepatic triglyceride (TG) levels (up to 528%) in mice. EtFSC treatment (1 or 5 g/kg/day for 7 days; from Day 1 to 7 or from Day 8 to 14, i.g.) significantly decreased the hepatic TG level (down to 35%) and slightly increased the hepatic index (by 8%) in hypercholesterolemic mice. Whereas fenofibrate treatment (0.1 g/kg/day for 7 days, i.g.) significantly lowered the hepatic TG level (by 61%), it elevated the hepatic index (by 77%) in hypercholesterolemic mice. Acute toxicity test showed that EtFSC was relatively non-toxic, with an LD50 value of 35.63 ± 6.46 g/kg in mice. The results indicate that EtFSC treatment can invariably decrease hepatic TG in hypercholesterolemic mice, as assessed by both preventive and therapeutic protocols, suggesting its potential use for fatty liver treatment. PMID:19592476

  19. Effect of acute treatment with cadmium on ethanol anesthesia, body termperature, and synaptosomal Na/sup +/-K/sup +/-ATPase of rat brain

    SciTech Connect

    Magour, S.; Kristof, V.; Baumann, M.; Assmann, G.

    1981-12-01

    The effect of a single intraperitoneal dose of 0.56, 1.12, and 1.68 mg cadmium/kg on the duration of ethanol-induced sleep was investigated in male rats. Cadmium potentiated ethanol sleeping time in a dose dependent manner up to 300% over controls. No significant difference in the elimination rate of ethanol from blood and brain and observed between control and cadmium-pretreated rats. Cadmium slightly inhibited the hepatic alcohol dehydrogenase in vivo and also potentiated ethanol hypothermia but these changes did not play a significant role in the observed prolongation of ethanol sleeping time. However, cadmium and ethanol additively inhibited brain synaptosomal Na/sup +/-K/sup +/-ATPase in a noncompetitive manner. The results so far indicate that cadmium may increase brain responsiveness toward ethanol partly through inhibition of snaptosomal Na/sup +/-K/sup +/-ATPase.

  20. Ethanol Concentration-Dependent Alterations in Gene Expression During Acute Binge Drinking in the HIV-1 Transgenic Rat

    PubMed Central

    Sarkar, Sraboni; Chang, Sulie L

    2013-01-01

    Background Binge drinking of high ethanol (EtOH) concentration beverages is common among young adults and can be a risk factor for exposure to sexually transmitted diseases, including HIV-1. We used a novel noninfectious HIV-1 transgenic (HIV-1Tg) rat model that mimics HIV-1 patients in terms of altered immune responses and deficits in cognitive learning and memory to investigate EtOH concentration-dependent effects on 48 alcohol-modulated genes during binge EtOH administration. Methods HIV-1Tg and control F344 rats were administered water, 8% EtOH, or 52% EtOH by gavage (i.g.) for 3 days (2.0 g/kg/d). Two hours after final treatment, blood, liver, and spleen were collected from each animal. Serum blood EtOH concentration (BEC) was measured, and gene expression in the liver and spleen was determined using a specifically designed PCR array. Results The BEC was significantly higher in the 52% EtOH-treated HIV-1Tg rats compared with the 8% EtOH group; however, the BEC was higher in the 8% EtOH-treated control rats compared with the 52% EtOH group. There was no change in expression of the EtOH metabolism-related genes, Adh1, Adh4, and Cyp2e1, in either the 8 or 52% EtOH-treated HIV-1Tg rats, whereas expression of those genes was significantly higher in the liver of the 52% EtOH control rats, but not in the 8% EtOH group. In the HIV-1Tg rats, expression of the GABAA, metabotropic glutamate, and dopamine neurotransmitter receptor genes was significantly increased in the spleen of the 52% EtOH group, but not in the 8% EtOH group, whereas no change was observed in those genes in either of the control groups. Conclusions Our data indicate that, in the presence of HIV-1 infection, EtOH concentration-dependent binge drinking can have significantly different molecular effects. PMID:23413777

  1. 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. ...

  2. GM1 ganglioside reduces the motor incoordination and loss of righting reflex caused by acute ethanol in C57BL/6J mice

    SciTech Connect

    Wallis, C.; Rezazadeh, S.M.; Forster, M.J.; Lal, H. )

    1992-02-26

    Ethanol produces its intoxicating effects by modifying neuronal membranes. Gangliosides stabilize neuronal membranes and promote their recovery from a variety of insults. In this experiment, the efficacy of GM1(i.p.) to reverse ethanol intoxication was evaluated in male mice trained to run on a constantly accelerating rotorod. When mice were tested 15-min following saline or ethanol GM1 pre-treatment reduced rotorod performance by 15% but was ineffective in modifying the ethanol-impaired performance. However, when mice were tested at 15, 35, 55, 75, and 95 min intervals following ethanol, GM1 pre-treatments dose-dependently reduced the efficacy and duration of ethanol in producing motor incoordination. Further, GM1 given prior to ethanol significantly prolonged the time to onset of the loss of righting reflex from 1.4 to 1.9 min, and reduced the duration of the righting-reflex loss from 94 to 77 min. This GM1 effect was seen at 24 h, but not at 48 or 72 h after its administration. The blood ethanol concentration at awakening was significantly higher in 24h GM1-treated animals than in controls suggesting that the GM1 effect was not due to an alteration in ethanol clearance. These findings support the hypothesis that GM1 promotes recovery from ethanol intoxication via a neuroprotective mechanism.

  3. Ethanol Basics

    SciTech Connect

    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.

  4. Ethanol Production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book chapter reviews the current process technologies for fuel ethanol production. In the US, almost all commercial fuel ethanol is produced from corn whereas cane sugar is used almost exclusively in Brazil. In Europe, two major types of feedstock considered for fuel ethanol production are be...

  5. Chronic treatment with prazosin or duloxetine lessens concurrent anxiety-like behavior and alcohol intake: evidence of disrupted noradrenergic signaling in anxiety-related alcohol use

    PubMed Central

    Skelly, Mary J; Weiner, Jeff L

    2014-01-01

    Background Alcohol use disorders have been linked to increased anxiety, and enhanced central noradrenergic signaling may partly explain this relationship. Pharmacological interventions believed to reduce the excitatory effects of norepinephrine have proven effective in attenuating ethanol intake in alcoholics as well as in rodent models of ethanol dependence. However, most preclinical investigations into the effectiveness of these drugs in decreasing ethanol intake have been limited to acute observations, and none have concurrently assessed their anxiolytic effects. The purpose of these studies was to examine the long-term effectiveness of pharmacological interventions presumed to decrease norepinephrine signaling on concomitant ethanol self-administration and anxiety-like behavior in adult rats with relatively high levels of antecedent anxiety-like behavior. Methods Adult male Long-Evans rats self-administered ethanol on an intermittent access schedule for eight to ten weeks prior to being implanted with osmotic minipumps containing either an a1-adrenoreceptor antagonist (prazosin, 1.5 mg/kg/day), a β1/2-adrenoreceptor antagonist (propranolol, 2.5 mg/kg/day), a serotonin/norepinephrine reuptake inhibitor (duloxetine, 1.5 mg/kg/day) or vehicle (10% dimethyl sulfoxide). These drugs were continuously delivered across four weeks, during which animals continued to have intermittent access to ethanol. Anxiety-like behavior was assessed on the elevated plus maze before treatment and again near the end of the drug delivery period. Results Our results indicate that chronic treatment with a low dose of prazosin or duloxetine significantly decreases ethanol self-administration (P < 0.05). Furthermore, this decrease in drinking is accompanied by significant reductions in the expression of anxiety-like behavior (P < 0.05). Conclusions These findings suggest that chronic treatment with putative inhibitors of central noradrenergic signaling may attenuate ethanol intake via a

  6. Effect of chronic ethanol consumption on glycosylation processes in rat liver microsomes and Golgi apparatus.

    PubMed

    Cottalasso, D; Gazzo, P; Dapino, D; Domenicotti, C; Pronzato, M A; Traverso, N; Bellocchio, A; Nanni, G; Marinari, U M

    1996-01-01

    Previous studies have demonstrated that acute ethanol intoxication affects various steps of protein glycosylation at the level of rat liver endoplasmic reticulum and Golgi apparatus. The aim of this investigation was to demonstrate whether chronic ethanol intake can induce definitive changes of liver glycoprotein processing. Rats were given ethanol by liquid diet for 8 weeks. At the end of this period the triglyceride levels in liver homogenate and microsomes were significantly higher than in controls. Isolated hepatocytes prelabelled with [3H]Na palmitate and [14C]glucosamine showed a significant storage of the lipid and carbohydrate radioactivity in microsomes and Golgi apparatus and a significant impairment of labelled glycolipoprotein secretion. Changes of the glycosylation steps were observed both in endoplasmic reticulum and in Golgi apparatus: in the former the levels of dolichyl phosphate, which is rate-limiting for the synthesis of glycoprotein, showed a significant reduction; in the latter the activity of the main enzymes responsible for the terminal glycosylation process was significantly decreased. These data suggest that an impairment of glycoprotein maturation may be involved in the pathogenesis of liver injury induced by chronic ethanol intake. PMID:8672174

  7. Fuel ethanol

    SciTech Connect

    Not Available

    1989-02-01

    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 current local feedstock requirement.

  8. Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption

    PubMed Central

    Bell, Richard L.; Kimpel, Mark W.; McClintick, Jeanette N.; Strother, Wendy N.; Carr, Lucinda G.; Liang, Tiebing; Rodd, Zachary A.; Mayfield, R. Dayne; Edenberg, Howard J.; McBride, William J.

    2009-01-01

    The objective of this study was to determine the effects of binge-like alcohol drinking on gene expression changes in the nucleus accumbens (ACB) of alcohol-preferring (P) rats. Adult male P rats were given ethanol under multiple scheduled access (MSA; three 1-hr dark-cycle sessions/day) conditions for 8 weeks. For comparison purposes, a second ethanol drinking group was given continuous/daily alcohol access (CA; 24 hr/day). A third group was ethanol-naïve (W group). Average ethanol intakes for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hr after the last drinking episode, rats were euthanized, the brains extracted, and the ACB dissected. RNA was extracted and purified for microarray analysis. The only significant differences were between the CA and W groups (p < 0.01; Storey false discovery rate = 0.15); there were 374 differences in named genes between these 2 groups. There were 20 significant Gene Ontology (GO) categories, which included negative regulation of protein kinase activity, anti-apoptosis, and regulation of G-protein-coupled receptor signaling. Ingenuity® analysis indicated a network of transcription factors, involving oncogenes (Fos, Jun, Junb had higher expression in the ACB of the CA group), suggesting increased neuronal activity. There were 43 genes located within rat QTLs for alcohol consumption and preference; 4 of these genes (Tgfa, Hspa5, Mtus1 and Creb3l2) are involved in anti-apoptosis and increased transcription, suggesting that they may be contributing to cellular protection and maintaining high alcohol intakes. Overall, these findings suggest that chronic CA drinking results in genomic changes that can be observed during the early acute phase of ethanol withdrawal. Conversely, chronic MSA drinking, with its associated protracted withdrawal periods, results in genomic changes that may be masked by tight regulation of these genes following repeated experiences of ethanol withdrawal. PMID:19666046

  9. The effects of acute and chronic nicotine hydrogen (+)-tartrate administration and subsequent withdrawal on rat liver tryptophan pyrrolase activity and their comparison with those of morphine, phenobarbitone and ethanol.

    PubMed Central

    Badawy, A A; Evans, M

    1975-01-01

    Acute administration of nicotine hydrogen (+)-tartrate enhances the activity of rat liver tryptophan pyrrolase by a hormonal mechanism. Chronic nicotine treatment inhibits, and subsequent withdrawal enhances, the pyrrolase activity. The inhibition during chronic treatment is not due to a defective apoenzyme synthesis nor a decreased cofactor availability. Regeneration of liver NADP+ in vitro and in vivo reverses the inhibition. Chronic nicotine administration increases the liver NADPH concentration. The above effects of nicotine resemble to a remarkable degree those previously shown for morphine, phenobarbitone and ethanol. All effects are compared, and their possible significance in relation to drug dependence is discussed. PMID:989

  10. Novel Comparative Pattern Count Analysis Reveals a Chronic Ethanol-Induced Dynamic Shift in Immediate Early NF-κB Genome-wide Promoter Binding During Liver Regeneration

    PubMed Central

    Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

    2016-01-01

    Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1h post PHx. This set was associated with regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1h binding targets showed ethanol-specific differential expression through 6h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx. PMID:26847025

  11. Adolescent binge-like ethanol exposure reduces basal α-MSH expression in the hypothalamus and the amygdala of adult rats

    PubMed Central

    Lerma-Cabrera, Jose Manuel; Carvajal, Francisca; Alcaraz-Iborra, Manuel; de la Fuente, Leticia; Navarro, Montserrat; Thiele, Todd E.; Cubero, Inmaculada

    2013-01-01

    Melanocortins (MC) are central peptides that have been implicated in the modulation of ethanol consumption. There is experimental evidence that chronic ethanol exposure reduces α-MSH expression in limbic and hypothalamic brain regions and alters central pro-opiomelanocortin (POMC) mRNA activity in adult rats. Adolescence is a critical developmental period of high vulnerability in which ethanol exposure alters corticotropin releasing factor, neuropeptide Y, substance P and neurokinin neuropeptide activities, all of which have key roles in ethanol consumption. Given the involvement of MC and the endogenous inverse agonist AgRP in ethanol drinking, here we evaluate whether a binge-like pattern of ethanol treatment during adolescence has a relevant impact on basal and/or ethanol-stimulated α-MSH and AgRP activities during adulthood. To this end, adolescent Sprague-Dawley rats (beginning at PND25) were pre-treated with either saline (SP group) or binge-like ethanol exposure (BEP group; 3.0 g/kg given in intraperitoneal (i.p.) injections) of one injection per day over two consecutive days, followed by 2 days without injections, repeated for a total of 8 injections. Following 25 ethanol-free days, we evaluated α-MSH and AgRP immunoreactivity (IR) in the limbic and hypothalamic nuclei of adult rats (PND63) in response to ethanol (1.5 or 3.0 g/kg i.p.) and saline. We found that binge-like ethanol exposure during adolescence significantly reduced basal α-MSH IR in the central nucleus of the amygdala (CeA), the arcuate nucleus (Arc) and the paraventricular nucleus of the hypothalamus (PVN) during adulthood. Additionally, acute ethanol elicited AgRP IR in the Arc. Rats given the adolescent ethanol treatment required higher doses of ethanol than saline-treated rats to express AgRP. In light of previous evidence that endogenous MC and AgRP regulate ethanol intake through MC-receptor signaling, we speculate that the α-MSH and AgRP disturbances induced by binge-like ethanol

  12. Experimental Traumatic Brain Injury Alters Ethanol Consumption and Sensitivity

    PubMed Central

    Lowing, Jennifer L.; Susick, Laura L.; Caruso, James P.; Provenzano, Anthony M.; Raghupathi, Ramesh

    2014-01-01

    Abstract Altered alcohol consumption patterns after traumatic brain injury (TBI) can lead to significant impairments in TBI recovery. Few preclinical models have been used to examine alcohol use across distinct phases of the post-injury period, leaving mechanistic questions unanswered. To address this, the aim of this study was to describe the histological and behavioral outcomes of a noncontusive closed-head TBI in the mouse, after which sensitivity to and consumption of alcohol were quantified, in addition to dopaminergic signaling markers. We hypothesized that TBI would alter alcohol consumption patterns and related signal transduction pathways that were congruent to clinical observations. After midline impact to the skull, latency to right after injury, motor deficits, traumatic axonal injury, and reactive astrogliosis were evaluated in C57BL/6J mice. Amyloid precursor protein (APP) accumulation was observed in white matter tracts at 6, 24, and 72 h post-TBI. Increased intensity of glial fibrillary acidic protein (GFAP) immunoreactivity was observed by 24 h, primarily under the impact site and in the nucleus accumbens, a striatal subregion, as early as 72 h, persisting to 7 days, after TBI. At 14 days post-TBI, when mice were tested for ethanol sensitivity after acute high-dose ethanol (4 g/kg, intraperitoneally), brain-injured mice exhibited increased sedation time compared with uninjured mice, which was accompanied by deficits in striatal dopamine- and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32) phosphorylation. At 17 days post-TBI, ethanol intake was assessed using the Drinking-in-the-Dark paradigm. Intake across 7 days of consumption was significantly reduced in TBI mice compared with sham controls, paralleling the reduction in alcohol consumption observed clinically in the initial post-injury period. These data demonstrate that TBI increases sensitivity to ethanol-induced sedation and affects downstream signaling mediators of

  13. Acute Effects of Energy Deficit Induced by Moderate-Intensity Exercise or Energy-Intake Restriction on Postprandial Lipemia in Healthy Girls.

    PubMed

    Thackray, Alice Emily; Barrett, Laura Ann; Tolfrey, Keith

    2015-05-01

    Eleven healthy girls (mean ± SD: age 12.1 ± 0.6 years) completed three 2-day conditions in a counterbalanced, crossover design. On day 1, participants either walked at 60 (2)% peak oxygen uptake (energy deficit 1.55[0.20] MJ), restricted food energy intake (energy deficit 1.51[0.25] MJ) or rested. On day 2, capillary blood samples were taken at predetermined intervals throughout the 6.5 hr postprandial period before, and following, the ingestion of standardized breakfast and lunch meals. Fasting plasma triacylglycerol concentrations (TAG) was 29% and 13% lower than rest control in moderate-intensity exercise (effect size [ES] = 1.39, p = .01) and energy-intake restriction (ES = 0.57, p = .02) respectively; moderate-intensity exercise was 19% lower than energy-intake restriction (ES = 0.82, p = .06). The moderate-intensity exercise total area under the TAG versus time curve was 21% and 13% lower than rest control (ES = 0.71, p = .004) and energy-intake restriction (ES = 0.39, p = .06) respectively; energy-intake restriction was marginally lower than rest control (-10%; ES = 0.32, p = .12). An exercise-induced energy deficit elicited a greater reduction in fasting plasma TAG with a trend for a larger attenuation in postprandial plasma TAG than an isoenergetic diet-induced energy deficit in healthy girls. PMID:25389209

  14. Comparative acute inhalation toxicity of a saline suspension and an ethanol solution of t-2 mycotoxin in mice. (Reannouncement with new availability information)

    SciTech Connect

    Creasia, D.A.; Thurman, J.D.

    1993-12-31

    We compared retention, distribution, toxicity, and histopathological change in mice after exposure to aerosols of T-2 suspended in saline or dissolved in ethanol. We found that the LC50 for mice exposed for 10 min to an aerosol of a saline suspension of T-2 was 0.035 plus or minus 0.02 T-2 per liter of air, which was lower than the LC50 (0.380 plus or minus 0.08 mg T-2 per liter air) for an aerosol of T-2 dissolved in ethanol. However, within about 15 min postexposure, most of the T-2 deposited in the respiratory tract was translocated from the respiratory tract regardless of whether the T-2 aerosol was from a saline suspension or ethanol solution. Also, although T-2 is an inflammatory agent to dermis and gastrointestinal epithelium, T-2 from either aerosol did not produce any histological evidence of inflammation in the respiratory tract.

  15. The addition of a protein-rich breakfast and its effects on acute appetite control and food intake in ‘breakfast-skipping’ adolescents

    PubMed Central

    Leidy, HJ; Racki, EM

    2014-01-01

    Background Breakfast skipping (BS) is closely associated with overeating (in the evening), weight gain and obesity. It is unclear whether the addition of breakfast, with emphasis on dietary protein, leads to better appetite and energy intake regulation in adolescents. Objective The purpose of the study was to examine the impact of addition of a normal-protein (PN) breakfast vs protein-rich (PR) breakfast on appetite and food intake in ‘breakfast-skipping’ adolescents. Subjects and Design A total of 13 adolescents (age 14.3 ± 0.3 years; body mass index percentile 79 ± 4 percentile; skipped breakfast 5 ± 1× per week) randomly completed 3 testing days that included a PN (18 ± 1 g protein), PR (48 ± 2 g protein) or BS. Breakfast was 24% of estimated daily energy needs. Appetite, satiety and hormonal responses were collected over 5 h followed by an ad libitum lunch and 24-h food intake assessments. Results Perceived appetite was not different following PN vs BS; PR led to greater reductions vs BS (P<0.01) and PN (P< 0.001). Fullness was greater following both breakfast meals vs BS (P<0.01) but was not different between meals. Ghrelin was not different among treatments. Greater PYY concentrations were observed following both breakfast meals vs BS (P<0.01) but was not different between meals. Lunch energy intake was not different following PN vs BS; PR led to fewer kcal consumed vs BS (P<0.01) and PN (P<0.005). Daily food intake was not different among treatments. Conclusions Breakfast led to increased satiety through increased fullness and PYY concentrations in ‘breakfast skipping’ adolescents. A breakfast rich in dietary protein provides additional benefits through reductions in appetite and energy intake. These findings suggest that the addition of a protein-rich breakfast might be an effective strategy to improve appetite control in young people. PMID:20125103

  16. Acute intake assessment: evolution within the Codex Committee on Pesticide Residues. WHO Joint Secretary of the Joint FAO/WHO meeting on pesticide residues JMPR.

    PubMed

    Herrman, J L

    2000-07-01

    The Codex Committee on Pesticide Residues (CCPR), in its development of international standards, has been considering during the last few years the implications of residues of acutely toxic pesticides in food commodities. CCPR has asked its scientific advisory body, the Joint FAO/WHO Meeting on Pesticide Residues (JMPR), for advice on the safety of the standards that are being developed. This work began in 1993. The 1994 JMPR first decided to use the 'acute reference dose' as a toxicological benchmark for a 'short-term ADI'. A number of acute reference doses have been allocated at subsequent meetings. The 1998 JMPR decided to consider the allocation of an acute reference dose whenever a full evaluation of a pesticide is undertaken. General guidance for the allocation of an acute reference dose was provided by the 1998 JMPR, which is discussed in this paper. PMID:10983577

  17. Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol)

    PubMed Central

    Dumont, Glenn J. H.; van Gerven, Joop M. A.; Buitelaar, Jan K.; Verkes, Robbert-Jan

    2010-01-01

    Rationale Typical users of 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”) are polydrug users, combining MDMA with alcohol or cannabis [most active compound: delta-9-tetrahydrocannabinol (THC)]. Objectives The aim of the present study was to investigate whether co-administration of alcohol or THC with MDMA differentially affects ongoing electroencephalogram (EEG) oscillations compared to the administration of each drug alone. Methods In two separate experiments, 16 volunteers received four different drug conditions: (1) MDMA (100 mg); (2) alcohol clamp (blood alcohol concentration = 0.6‰) or THC (inhalation of 4, 6 and 6 mg, interval of 1.5 h); (3) MDMA in combination with alcohol or THC; and (4) placebo. Before and after drug administration, electroencephalography was recorded during an eyes closed resting state. Results Theta and alpha power increased after alcohol intake compared to placebo and reduced after MDMA intake. No interaction between alcohol and MDMA was found. Significant MDMA × THC effects for theta and lower-1-alpha power indicated that the power attenuation after the combined intake of MDMA and THC was less than the sum of each drug alone. For the lower-2-alpha band, the intake of MDMA or THC alone did not significantly affect power, but the intake of combined MDMA and THC significantly decreased lower-2-alpha power. Conclusions The present findings indicate that the combined intake of MDMA and THC, but not of MDMA and alcohol, affects ongoing EEG oscillations differently than the sum of either one drug alone. Changes in ongoing EEG oscillations may be related to the impaired task performance that has often been reported after drug intake. PMID:20924751

  18. Acute effects of acarbose on post-prandial glucose and triglycerides in type 2 diabetics following intake of different Malaysian foods.

    PubMed

    Nawawi, H M; Yazid, T N; Ismail, F; Khalid, B A

    2000-03-01

    Acarbose inhibits intestinal alpha-glucosidases resulting in diminished and delayed postprandial hyperglycaemia (PPH). Studies on effects of acarbose on postprandial lipaemia (PPL) have been inconclusive. Little is known about the effects of acarbose on PPH and PPL following intake of a polysaccharide diet. We studied 30 type 2 diabetic patients on dietary and/or oral hypoglycaemic agent(s). Thirty patients were recruited for food A (nasi lemak), 28 for food B (mee goreng) and 28 for food C (roti telur), which represent the typical diets of the three main races in Malaysia. Serial blood samples were taken at 15 min before and up to 240 min after each food intake, without acarbose. Subsequently, three doses of 50 mg acarbose were given orally and the same procedure was repeated the following day. There were significantly lower mean increments in plasma glucose levels after compared to before acarbose treatment 30, 45 and 60 min for food A and at 30, 45, 60, 120, 180 and 240 min for food C, but no significant difference was noted for food B. There was a significantly lower mean fasting glucose level after compared with before acarbose treatment following intake of food A and C but not food B. Short-term treatment with acarbose caused significant diminished and delayed PPH response with food A and C but not with food B. Acarbose was more effective in reducing PPH response in polysaccharide foods with a higher and earlier postprandial glucose peak than in those with a lower and lagged peak. There were no significant differences in the mean fasting or postprandial triglyceride levels before and after acarbose treatment, following intake of all three foods for up to 4 hours. Depending on the food absorption pattern, overnight low dose treatment with acarbose leads to diminished fasting and peak plasma glucose levels, and delayed PPH but insignificant reduction in postprandial lipaemia in poorly controlled type 2 diabetics following intake of racially different Malaysian

  19. Acute effects of protein composition and fibre enrichment of yogurt consumed as snacks on appetite sensations and subsequent ad libitum energy intake in healthy men.

    PubMed

    Doyon, Caroline Y; Tremblay, Angelo; Rioux, Laurie-Eve; Rhéaume, Caroline; Cianflone, Katherine; Poursharifi, Pegah; Turgeon, Sylvie L

    2015-10-01

    The objective of the study was to assess the impact of protein composition and/or fibre enrichment of yogurt on appetite sensations and subsequent energy intake. In this double-blind crossover study, 20 healthy men (aged 32.4 ± 9.1 years) were submitted to 5 randomized testing sessions, during which they had to consume 5 isocaloric and isonproteinemic yogurt snacks (120-g servings, ∼230 kJ, ∼4.5 g protein) differing by their casein-to-whey protein ratio (C:W) or dietary fibre content: (i) control C:W = 2.8:1; (ii) high whey (HW) C:W = 1.5:1, and fibre-enriched formulations using control; (iii) 2.4 g of inulin; (iv) 1.9 g of inulin and 0.5 g of β-glucan (+IN-βG); and (v) 0.5 g of β-glucan. Appetite sensations were assessed using 150-mm visual analog scales. Plasma variables (glucose, insulin, ghrelin) were measured at 30-min intervals post-yogurt consumption for 2 h. Finally, energy intakes during ad libitum lunches offered 2 h after yogurt snacks were recorded. None of the yogurts impacted appetite sensations. Ad libitum energy intake was significantly different only between HW and control yogurts (-812 kJ; p = 0.03). Regarding post-yogurt plasma variables, a significant difference was found only between ghrelin area under the curve of the +IN-βG and the HW yogurts (-15 510 pmol/L per 120 min, p = 0.04). In conclusion, although appetite sensations were not influenced by variations in yogurts' protein compositions, a reduced energy intake was observed during the ad libitum lunch after the HW yogurt that may be attributable to its lower C:W. Surprisingly, the fibre enrichments studied did not exert effect on appetite sensations and energy intake. PMID:26394259

  20. Xanthine oxidase status in ethanol-intoxicated rat liver.

    PubMed

    Abbondanza, A; Battelli, M G; Soffritti, M; Cessi, C

    1989-12-01

    The status of xanthine oxidase in ethanol-induced liver injury has been investigated in the rat, by acute and chronic ethanol treatments. A 38% increase of the enzyme O-form was observed after repeated ethanol administration. Chronic intoxication caused a significant decrease of total xanthine oxidase activity after both prolonged ethanol feeding and life span ethanol ingestion. The intermediate D/O-form of xanthine oxidase (that can act either as an oxidase or as a dehydrogenase, being able to react with O2 as well as with NAD+ as electron acceptor) increased 5.5-fold after prolonged ethanol feeding. PMID:2690670

  1. 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

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

    PubMed

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

    2016-04-01

    The orexin/hypocretin (ORX) system plays a major role in motivation for natural and drug rewards. In particular, a number of studies have shown that ORX signaling through the orexin 1 receptor (OX1R) regulates alcohol seeking and consumption. Despite the association between ORX signaling and motivation for alcohol, no study to date has investigated what role the ORX system plays in alcohol dependence, an understanding of which would have significant clinical relevance. This study was designed to evaluate the effect of the highly selective OX1R antagonist GSK1059865 on voluntary ethanol intake in ethanol-dependent and control non-dependent mice. Mice were subjected to a protocol in which they were evaluated for baseline ethanol intake and then exposed to intermittent ethanol or air exposure in inhalation chambers. Each cycle of chronic intermittent ethanol (CIE), or air, exposure was followed by a test of ethanol intake. Once the expected effect of increased voluntary ethanol intake was obtained in ethanol dependent mice, mice were tested for the effect of GSK1059865 on ethanol and sucrose intake. Treatment with GSK1059865 significantly decreased ethanol drinking in a dose-dependent manner in CIE-exposed mice. In contrast GSK1059865 decreased drinking in air-exposed mice only at the highest dose used. There was no effect of GSK1059865 on sucrose intake. Thus, ORX signaling through the OX1R, using a highly-selective antagonist, has a profound influence on high levels of alcohol drinking induced in a dependence paradigm, but limited or no influence on moderate alcohol drinking or sucrose drinking. These results indicate that the ORX system may be an important target system for treating disorders of compulsive reward seeking such as alcoholism and other addictions in which motivation is strongly elevated. PMID:26851547

  3. Role of hypothermia in ethanol-induced conditioned taste aversion.

    PubMed

    Cunningham, C L; Hawks, D M; Niehus, D R

    1988-01-01

    Two experiments examined the effect of ambient temperature during ethanol exposure on development of conditioned taste aversion to saccharin. In both studies, male albino rats receiving saccharin-ethanol (1.5 g/kg, IP) pairings followed by 6-h exposure to a 32 degrees C environment developed a weaker saccharin aversion than did rats experiencing ethanol at room temperature. Exposure to the warm environment reduced ethanol-induced hypothermia, but enhanced ethanol's motor-impairing effect. The influence of ambient temperature on ethanol-induced taste aversion may be due to changes in body temperature, neural sensitivity, or elimination rate. Although alternative accounts cannot be entirely dismissed, this outcome suggests that ethanol-induced hypothermia plays a role in determining strength of conditioned taste aversion and thus may be involved in the regulation of oral ethanol intake in rats. PMID:3137617

  4. Protective effects of alginate–chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. (Zuojin Pill) against ethanol-induced acute gastric mucosal injury in rats

    PubMed Central

    Wang, Qiang-Song; Zhu, Xiao-Ning; Jiang, Heng-Li; Wang, Gui-Fang; Cui, Yuan-Lu

    2015-01-01

    Zuojin Pill (ZJP), a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in a ratio of 6:1 (w/w) and was first recorded in “Danxi’s experiential therapy” for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss.) Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the mucoadhesive microspheres loaded with alkaloids reduce the inflammatory response by decreasing the levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), downregulating the mRNA expression of inducible nitric oxide synthase, TNF-α, and IL-1β in gastric mucosa. All the results indicate that mucoadhesive microspheres loaded with alkaloids could not only increase the residence time of alkaloids in rat stomach, but also exert gastroprotective effects through reducing the inflammatory response on ethanol-induced gastric mucosal damage. Thus

  5. Low dose ethanol consumption improves insulin sensitivity in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While chronic consumption of high doses of ethanol is well known to have adverse health consequences, intake of low doses have been reported to improve several markers of health outcomes. Published results from our laboratory using total enteral nutrition (TEN) in rats, in which ethanol-containing d...

  6. Novel role of Zn(II)-curcumin in enhancing cell proliferation and adjusting proinflammatory cytokine-mediated oxidative damage of ethanol-induced acute gastric ulcers.

    PubMed

    Mei, Xueting; Xu, Donghui; Xu, Sika; Zheng, Yanping; Xu, Shibo

    2012-04-15

    Alcohol consumption can induce gastric ulcers and zinc deficiency. Zinc complexes were reported to have anti-ulcer activity as it acts as an anti-inflammatory and antioxidant. Zn(II)-curcumin complex and its solid dispersions (SDs) were synthesized and evaluated for its gastroprotective activity and mechanism against ethanol-induced ulcer. The Swiss murine fibroblast cell line (3T3) was used as an alternative in vitro model to evaluate the effects of Zn(II)-curcumin on cell proliferation. Zn(II)-curcumin were administered orally for seven consecutive days prior to induction of ulcers using ethanol. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that solid dispersions (SDs) of Zn(II)-curcumin (2.5-20 μM) enhanced the proliferation of 3T3 cells more significantly than curcumin at the same concentrations (P<0.01). Oral administration of Zn(II)-curcumin (12, 24 and 48 mg/kg) SDs dose-dependently prevented formation of ulcer lesions induced by ethanol. The levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and oxidative stress superoxide dismutase (SOD), glutathione peroxidase (GPX-Px), malonaldehyde (MDA) and H(+)-K(+)-ATPase were in the rats exposed to ethanol in ulceration have been altered. Zn(II)-curcumin prevented formation of ulcer lesions, significantly inhibited TNF-α and IL-6 mRNA expression, increased the activity of SOD and GSH-Px, reduced MDA levels and H(+)-K(+)-ATPase in mucosa of rats compared to controls (P<0.05). These findings suggest that the gastroprotective activity of Zn(II)-curcumin complex might contribute in stimulating cell proliferation and adjusting the proinflammatory cytokine-mediated oxidative damage to the gastric mucosa. PMID:22465177

  7. Anti-Ulcerogenic Properties of Lycium chinense Mill Extracts against Ethanol-Induced Acute Gastric Lesion in Animal Models and Its Active Constituents.

    PubMed

    Olatunji, Opeyemi J; Chen, Hongxia; Zhou, Yifeng

    2015-01-01

    The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA) against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO) activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE) staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-α, IL-6, and IL-1β in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-κB in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers. PMID:26694339

  8. Acute Toxicity and Gastroprotection Studies of a New Schiff Base Derived Manganese (II) Complex against HCl/Ethanol-Induced Gastric Ulcerations in Rats

    PubMed Central

    Ibrahim, Mohamed Yousif; Hashim, Najihah Mohd; Dhiyaaldeen, Summaya M.; Al-Obaidi, Mazen M.Jamil; El-Ferjani, Rashd M.; Adam, Hoyam; Alkotaini, Bassam; Batran, Rami Al; Ali, Hapipah Mohd

    2016-01-01

    Manganese is a crucial element for health. In this study, the gastroprotective efficacy of Mn (II) complex (MDLA) against acidified ethanol (HCl/Ethanol)-induced gastric ulceration in rats was evaluated. The animals were distributed into 5 groups. Groups 1 and 2 received carboxymethylcellulose (CMC), group 3 was pretreated with omeprazole, and groups 4 and 5 were given 10 and 20 mg/kg of MDLA, respectively. After one hour, CMC and HCl/Ethanol were given to groups 2–5 whilst the animals in group 1 were ingested with CMC. After sacrifice, gastric lesions were evaluated by wall mucus, gross appearance, histology, antioxidant enzymes and immunohistochemistry. Group 2 displayed severe gastric damage with a significant reduction in wall mucus. Conversely, gastric lesions were reduced in groups 3–5 by 85.72%, 56.51% and 65.93%, respectively. The rats in groups 3–5 showed up-regulation of heat shock protein 70 (Hsp70) with down-regulation of Bcl-2-associated protein x (Bax). Pretreatment with omeprazole or MDLA led to an increase in the uptake of Periodic Acid Schiff (PAS) stain in the glandular part of the gastric tissue, raised levels of prostaglandin E2 (PGE2) and superoxide dismutase (SOD), and a reduction in malondialdehyde (MDA) concentrations. These results suggested the gastroprotective action of Mn (II) complex. PMID:27229938

  9. Acute Toxicity and Gastroprotection Studies of a New Schiff Base Derived Manganese (II) Complex against HCl/Ethanol-Induced Gastric Ulcerations in Rats.

    PubMed

    Ibrahim, Mohamed Yousif; Hashim, Najihah Mohd; Dhiyaaldeen, Summaya M; Al-Obaidi, Mazen M Jamil; El-Ferjani, Rashd M; Adam, Hoyam; Alkotaini, Bassam; Batran, Rami Al; Ali, Hapipah Mohd

    2016-01-01

    Manganese is a crucial element for health. In this study, the gastroprotective efficacy of Mn (II) complex (MDLA) against acidified ethanol (HCl/Ethanol)-induced gastric ulceration in rats was evaluated. The animals were distributed into 5 groups. Groups 1 and 2 received carboxymethylcellulose (CMC), group 3 was pretreated with omeprazole, and groups 4 and 5 were given 10 and 20 mg/kg of MDLA, respectively. After one hour, CMC and HCl/Ethanol were given to groups 2-5 whilst the animals in group 1 were ingested with CMC. After sacrifice, gastric lesions were evaluated by wall mucus, gross appearance, histology, antioxidant enzymes and immunohistochemistry. Group 2 displayed severe gastric damage with a significant reduction in wall mucus. Conversely, gastric lesions were reduced in groups 3-5 by 85.72%, 56.51% and 65.93%, respectively. The rats in groups 3-5 showed up-regulation of heat shock protein 70 (Hsp70) with down-regulation of Bcl-2-associated protein x (Bax). Pretreatment with omeprazole or MDLA led to an increase in the uptake of Periodic Acid Schiff (PAS) stain in the glandular part of the gastric tissue, raised levels of prostaglandin E2 (PGE2) and superoxide dismutase (SOD), and a reduction in malondialdehyde (MDA) concentrations. These results suggested the gastroprotective action of Mn (II) complex. PMID:27229938

  10. “Jello® Shots” and Cocktails as Ethanol Vehicles: Parametric Studies with High- and Low-Saccharin-Consuming Rats

    PubMed Central

    Dess, Nancy K.; Madkins, Chardonnay D.; Geary, Bree A.; Chapman, Clinton D.

    2013-01-01

    Naïve humans and rats voluntarily consume little ethanol at concentrations above ~6% due to its aversive flavor. Developing procedures that boost intake of ethanol or ethanol-paired flavors facilitates research on neural mechanisms of ethanol-associated behaviors and helps identify variables that modulate ethanol intake outside of the lab. The present study explored the impact on consumption of ethanol and ethanol-paired flavors of nutritionally significant parametric variations: ethanol vehicle (gelatin or solution, with or without polycose); ethanol concentration (4% or 10%); and feeding status (chow deprived or ad lib.) during flavor conditioning and flavor preference testing. Individual differences were modeled by testing rats of lines selectively bred for high (HiS) or low (LoS) saccharin intake. A previously reported preference for ethanol-paired flavors was replicated when ethanol had been drunk during conditioning. However, indifference or aversion to ethanol-paired flavors generally obtained when ethanol had been eaten in gelatin during conditioning, regardless of ethanol concentration, feeding status, or caloric value of the vehicle. Modest sex and line variations occurred. Engaging different behavioral systems when eating gelatin, rather than drinking solution, may account for these findings. Implications for parameter selection in future neurobiological research and for understanding conditions that influence ethanol intake outside of the lab are discussed. PMID:24284614

  11. Sex-dependent consequences of pre-pubertal gonadectomy: Social behavior, stress and ethanol responsivity.

    PubMed

    Kim, Esther U; Spear, Linda P

    2016-01-01

    Alcohol consumption can be enhanced or moderated by sensitivity to its aversive and appetitive properties, including positive social outcomes. These differences emerge post-pubertally, suggesting a potential role of gonadal hormones. To determine the role of gonadal hormones in sensitivity to the social impairing and social context-related attenuations in the aversive effects of ethanol, prepubertal male and female rats were gonadectomized (GX) or sham (SH) operated on postnatal day (P) 25, or left non-manipulated (NM). In adulthood (P70), rats were restrained for 90 min prior to challenge with 0.0 or 1.0 g/kg ethanol and social interaction (SI) testing. At P77, groups of 4 same-sex littermates from the same surgical condition were given access to a supersaccharin (SS) solution (3% sucrose, 0.125% saccharin), followed by an intraperitoneal injection of ethanol (0.0, 0.50, 1.0, 1.5 g/kg). Intakes of SS were examined 24h later for expression of conditioned taste aversions. Acute stress prior to SI testing increased frequency of play fighting in both sexes, whereas there were no GX effects on this measure, social investigation nor contact. GX, however, decreased baseline social preference (a social anxiety-like effect) in males, while inducing anxiolytic-like increases in baseline social preference in females. The social drinking test revealed that females developed ethanol conditioned taste aversions at a lower dose relative to males, regardless of surgical condition. These findings suggest a potential role for gonadal hormones in moderating social-anxiety like behaviors but not sensitivity to the social impairing effects of ethanol or ethanol's aversive consequences in a social context. PMID:26386303

  12. Peripheral oxytocin administration reduces ethanol consumption in rats

    PubMed Central

    MacFadyen, Kaley; Loveless, Rebecca; DeLucca, Brandon; Wardley, Krystal; Deogan, Sumeet; Thomas, Cameron; Peris, Joanna

    2016-01-01

    The neuropeptide oxytocin interacts with mesolimbic dopamine neurons to mediate reward associated with filial behaviors, but also other rewarding behaviors such as eating or taking drugs of abuse. Based on its efficacy to decrease intake of other abused substances, oxytocin administration is implicated as a possible treatment for excessive alcohol consumption. We tested this hypothesis by measuring ethanol intake in male Sprague–Dawley rats injected with oxytocin or saline using two different ethanol self-administration paradigms. First, a dose–response curve was constructed for oxytocin inhibition of fluid intake using a modified drinking-in-the-dark model with three bottles containing .05% saccharine, 10% ethanol in saccharine, and 15% ethanol in saccharine. Doses of oxytocin tested were 0.05, 0.1, 0.3, and 0.5 mg/kg (I.P.). Next, rats received 0.3 mg/kg oxytocin preceding operant sessions in which they were trained to lever-press for either plain gelatin or ethanol gelatin in order to compare oxytocin inhibition of ethanol intake versus caloric intake. For the three-bottle choice study, rats consumed significantly less ethanol when treated with the three higher doses of oxytocin on the injection day. In the operant study, 0.3 mg/kg oxytocin significantly decreased ethanol gel consumption to a greater extent than plain gel consumption, both in terms of the amount of gel eaten and calories consumed. These data affirm oxytocin's efficacy for decreasing ethanol intake in rats, and confirm clinical studies suggesting oxytocin as a potential treatment for alcoholism. PMID:26519603

  13. Anti-Ulcerogenic Effect of Methanolic Extracts from Enicosanthellum pulchrum (King) Heusden against Ethanol-Induced Acute Gastric Lesion in Animal Models

    PubMed Central

    Nordin, Noraziah; Salama, Suzy Munir; Golbabapour, Shahram; Hajrezaie, Maryam; Hassandarvish, Pouya; Kamalidehghan, Behnam; Majid, Nazia Abdul; Hashim, Najihah Mohd; Omar, Hanita; Fadaienasab, Mehran; Karimian, Hamed; Taha, Hairin; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

    2014-01-01

    A natural source of medicine, Enicosanthellum pulchrum is a tropical plant which belongs to the family Annonaceae. In this study, methanol extract from the leaves and stems of this species was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in rats. Seven groups of rats were assigned, groups 1 and 2 were given Tween 20 (10% v/v) orally. Group 3 was administered omeprazole 20 mg/kg (10% Tween 20) whilst the remaining groups received the leaf and stem extracts at doses of 150 and 300 mg/kg, respectively. After an additional hour, the rats in groups 2–7 received ethanol (95% v/v; 8 mL/kg) orally while group 1 received Tween 20 (10% v/v) instead. Rats were sacrificed after 1 h and their stomachs subjected to further studies. Macroscopically and histologically, group 2 rats showed extremely severe disruption of the gastric mucosa compared to rats pre-treated with the E. pulchrum extracts based on the ulcer index, where remarkable protection was noticed. Meanwhile, a significant percentage of inhibition was shown with the stem extract at 62% (150 mg/kg) and 65% (300 mg/kg), whilst the percentage with the leaf extract at doses of 150 and 300 mg/kg was 63% and 75%, respectively. An increase in mucus content, nitric oxide, glutathione, prostaglandin E2, superoxide dismutase, protein and catalase, and a decrease in malondialdehyde level compared to group 2 were also obtained. Furthermore, immunohistochemical staining of groups 4–7 exhibited down-regulation of Bax and up-regulation of Hsp70 proteins. The methanol extract from the leaves and the stems showed notable gastroprotective potential against ethanol. PMID:25379712

  14. Acute effects of different dietary polysaccharides added in milk on food intake, postprandial appetite and glycemic responses in healthy young females.

    PubMed

    Arshad, Muhammad Umair; Ishtiaq, Saima; Anjum, Faqir Muhammad; Saeed, Farhan; Chatha, Shahzad Ali Shahid; Imran, Ali

    2016-09-01

    In the present study we compared the postprandial glycemic and satiety responses of different dietary polysaccharides when added in milk (2% M.F.). The objective of this study was to evaluate different polysaccharides against postprandial glucose, appetite responses and food intake at subsequent meal. In a repeated measures design, 30 females (18-30 years) consumed 250 ml milk 2% M.F. (control), or milk with carrageenan (2.5 g), guar gum (2.5 g) and alginate (2.5 g), followed by an ad libitum pizza meal after 120 min. Alginate and guar gum addition resulted in lower caloric intake at subsequent pizza meal. The post-treatment (0-120 min) glucose and average appetite were suppressed by alginate and guar gum (p < 0.0001), with more pronounced effect of guar gum. However, alginate resulted in lower blood glucose (p < 0.0001) compared with control and carrageenan during post-treatment. Alginate and guar gum added beverages would be beneficial in short-term regulation of postprandial glycemia and satiety. PMID:27352777

  15. Acute exposure to ethanol potentiates human immunodeficiency virus type 1 Tat-induced Ca(2+) overload and neuronal death in cultured rat cortical neurons.

    PubMed

    Brailoiu, Eugen; Brailoiu, G Cristina; Mameli, Giuseppe; Dolei, Antonina; Sawaya, Bassel E; Dun, Nae J

    2006-02-01

    A significant number of human immunodeficiency virus type 1 (HIV-1)-infected patients are alcoholics. Either alcohol or HIV alone induces morphological and functional damage to the nervous system. HIV-1 Tat is a potent transcriptional activator of the viral promoter, with the ability to modulate a number of cellular regulatory circuits including apoptosis and to cause neuronal injury. To further evaluate the involvement of alcohol in neuronal injury, the authors examined the effect of ethanol on Tat-induced calcium responses in rat cerebral cortical neurons, using microfluorimetric calcium determination. HIV Tat protein (10 or 500 nM) elicited two types of calcium responses in cortical neurons: a fast-onset, short-lasting response and a slow-onset, sustained response. The responses were concentration-dependent and diminished in calcium-free saline. A short exposure to ethanol (50 mM) potentiated both types of calcium response, which was markedly decreased when the cells were pretreated with BAPTA-AM (20 microM). In addition, an increase in the neurotoxic effect of Tat, which was assessed by trypan blue exclusion assay, was observed. The result led the authors to conclude that alcohol exposure significantly potentiates Tat-induced calcium overload and neuronal death. PMID:16595370

  16. 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

  17. 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. PMID:27189965

  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. Carbohydrate intake.

    PubMed

    Leturque, Armelle; Brot-Laroche, Edith; Le Gall, Maude

    2012-01-01

    Carbohydrates represent more than 50% of the energy sources present in most human diets. Sugar intake is regulated by metabolic, neuronal, and hedonic factors, and gene polymorphisms are involved in determining sugar preference. Nutrigenomic adaptations to carbohydrate availability have been evidenced in metabolic diseases, in the persistence of lactose digestion, and in amylase gene copy number. Furthermore, dietary oligosaccharides, fermentable by gut flora, can modulate the microbiotal diversity to the benefit of the host. Genetic diseases linked to mutations in the disaccharidase genes (sucrase-isomaltase, lactase) and in sugar transporter genes (sodium/glucose cotransporter 1, glucose transporters 1 and 2) severely impact carbohydrate intake. These diseases are revealed upon exposure to food containing the offending sugar, and withdrawal of this sugar from the diet prevents disease symptoms, failure to thrive, and premature death. Tailoring the sugar composition of diets to optimize wellness and to prevent the chronic occurrence of metabolic diseases is a future goal that may yet be realized through continued development of nutrigenetics and nutrigenomics approaches. PMID:22656375

  20. The effects of acute and chronic administration of n-6 and n-3 polyunsaturated fatty acids on ethanol-induced gastric haemorrhage in rats.

    PubMed

    Hunter, B; McDonald, G S; Gibney, M J

    1992-05-01

    Female weanling rats in three equal groups (n 12) were given orally by intubation 1 ml micellar solution of taurocholic acid (10 mM) and either arachidonic acid (20:4 n-6), linoleic acid (18:2 n-6) or eicosapentaenoic acid (20:5 n-3) at a concentration of 120 mM. After 1 h the rats were given intragastrically 2 ml absolute ethanol and were killed 1 h later. Rats given oral 20:4 n-6 showed a significant reduction (P less than 0.05) in the extent (%) of gastric mucosal haemorrhage compared with either the rats given 20:5 n-3 or 18:2 n-6 (8.3 (SD 7.3), 23.2 (SD 10.4) and 21.4 (SD 10.4) respectively. In a second experiment, four equal groups (n 12) of female Wistar rats were fed for 5 weeks on either a control diet of standard laboratory rat food, or the same diet enriched with either maize oil or fish oil or butterfat at a level of 100 g/kg. Following a 24 h fast the rats received an intragastric dose of 2 ml ethanol and were killed 1 h later. Examination of the extent (%) of gastric lesion showed a significant reduction (P less than 0.05) with the feeding of either maize oil or fish oil compared with the controls (12.2 (SD 8.2), 15.3 (SD 13.2) and 29.3 (SD 14.0) respectively). The butterfat diet was not significantly different from the control diet (23.8 (SD 8.1)). PMID:1622986

  1. Ethanol drinking in socially housed squirrel monkeys.

    PubMed

    Mandillo, S; Titchen, K; Miczek, K A

    1998-07-01

    This study proposes a method to assess voluntary alcohol drinking in socially living squirrel monkeys. Group-housed squirrel monkeys were induced to drink a sucrose solution and subsequently an ethanol/sucrose solution in an experimental chamber attached to the home colony room, allowing the daily intake to be monitored for each individual without disrupting the social context. Sucrose concentration (0.03-0.6 M, corresponding to 1-20%) and ethanol concentration (0-4%) were gradually increased in tap water and in a 0.6 M (ca. 20%) sucrose solution during daily 30-min and 10-min sessions, respectively. Blood ethanol levels ranged from 10-50 mg/dl and remained below intoxication level. These experiments demonstrate that it is feasible to arrange conditions under which individual socially housed squirrel monkeys voluntarily drink a sweetened ethanol solution. PMID:10065925

  2. Social consequences of ethanol: Impact of age, stress, and prior history of ethanol exposure.

    PubMed

    Varlinskaya, Elena I; Spear, Linda P

    2015-09-01

    The adolescent period is associated with high significance of interactions with peers, high frequency of stressful situations, and high rates of alcohol use. At least two desired effects of alcohol that may contribute to heavy and problematic drinking during adolescence are its abilities to both facilitate interactions with peers and to alleviate anxiety, perhaps especially anxiety seen in social contexts. Ethanol-induced social facilitation can be seen using a simple model of adolescence in the rat, with normal adolescents, but not their more mature counterparts, demonstrating this ethanol-related social facilitation. Prior repeated stress induces expression of ethanol-induced social facilitation in adults and further enhances socially facilitating effects of ethanol among adolescent rats. In contrast, under normal circumstances, adolescent rats are less sensitive than adults to the social inhibition induced by higher ethanol doses and are insensitive to the socially anxiolytic effects of ethanol. Sensitivity to the socially anxiolytic effects of ethanol can be modified by prior stress or ethanol exposure at both ages. Shortly following repeated restraint or ethanol exposure, adolescents exhibit social anxiety-like behavior, indexed by reduced social preference, and enhanced sensitivity to the socially anxiolytic effects of ethanol, indexed through ethanol-associated reinstatement of social preference in these adolescents. Repeated restraint, but not repeated ethanol, induces similar effects in adults as well, eliciting social anxiety-like behavior and increasing their sensitivity to the socially anxiolytic effects of acute ethanol; the stressor also decreases sensitivity of adults to ethanol-induced social inhibition. The persisting consequences of early adolescent ethanol exposure differ from its immediate consequences, with males exposed early in adolescence, but not females or those exposed later in adolescence, showing social anxiety-like behavior when tested

  3. 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. PMID:26216835

  4. Development of a mouse model of ethanol addiction: naltrexone efficacy in reducing consumption but not craving.

    PubMed

    Fachin-Scheit, D J; Frozino Ribeiro, A; Pigatto, G; Oliveira Goeldner, F; Boerngen de Lacerda, R

    2006-09-01

    The aim of the present study was validating pharmacologically a mouse model of alcohol addiction. Mice (n = 60) were offered ethanol (5% and 10%) and water in a free choice paradigm consisting of four phases: free choice (10 weeks), withdrawal (2 weeks), re-exposure (2 weeks) and quinine- adulteration (2 weeks). Control mice (n = 10) had access to water. They were housed individually with food ad libitum. The animals' behaviour was evaluated at the beginning of the treatment and during the withdrawal period. After the exposure to the model, mice received i.p. naltrexone (0.0; 0.125; 2.0 and 16.0 mg/kg) or saline. Mice were characterized as: addicted (n = 15, preference for ethanol without reducing intake when ethanol were adulterated with quinine); heavy drinker (n = 14, preference for ethanol but reduced intake when ethanol were adulterated); and light drinker (n = 16, no preference for ethanol). Naltrexone reduced ethanol intake in the heavy and light groups (p intake. It is discussed that naltrexone may be acting in the positive reinforcing properties of ethanol but does not seem to have anti-craving properties. It was concluded that the addicted mice had a compulsive behavior manifested by the continued ethanol intake even under aversive conditions and under naltrexone treatment suggesting that this model might be useful to study addiction. PMID:16465467

  5. Ethanol and blood pressure in rats

    SciTech Connect

    Hatton, D.C.; Edgar, S.; McCarron, D.A. )

    1989-02-09

    Epidemiologists have identified alcohol as a risk factor in hypertension. Attempts to increase blood pressure in rats with chronic alcohol ingestion have met with mixed results. Some investigators have reported increases in blood pressure while others have reported decreases. Most investigators have given alcohol in the drinking water which produced differences in food intake across groups. To control for food intake, Wister rats were simultaneously pair fed a liquid diet with either ethanol as 35% of calories or a control diet using ARF/Israel pair-feeding devices. At 5 weeks of age, animals on ethanol diets had lower systolic blood pressure than control animals (145 (n-19) vs. 121 (n-19) mmHg). There was no difference in weight between ethanol and control animals. The same pattern of results was apparent at 7 weeks (143 (n-13) vs. 119 (n-13) mmHg) and 9 weeks (147 (n-7) vs. 124 (n-7)). The data indicate that ethanol produces hypotension in rats when food intake is controlled.

  6. PHYSIOLOGIC AND GENOMIC ANALYSES OF NUTRITION-ETHANOL INTERACTIONS DURING GESTATION: IMPLICATIONS FOR FETAL ETHANOL TOXICITY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutrition-ethanol (EtOH) interactions during gestation remain unclear, primarily due to the lack of appropriate rodent models. In the present report we utilize total enteral nutrition (TEN) to specifically understand the roles of nutrition and caloric intake in EtOH-induced fetal toxicity. Time-impr...

  7. Acute effects of pea protein and hull fibre alone and combined on blood glucose, appetite, and food intake in healthy young men--a randomized crossover trial.

    PubMed

    Mollard, Rebecca C; Luhovyy, Bohdan L; Smith, Christopher; Anderson, G Harvey

    2014-12-01

    Whether pulse components can be used as value-added ingredients in foods formulated for blood glucose (BG) and food intake (FI) control requires investigation. The objective of this study was to examine of the effects of pea components on FI at an ad libitum meal, as well as appetite and BG responses before and after the meal. In a repeated-measures crossover trial, men (n = 15) randomly consumed (i) pea hull fibre (7 g), (ii) pea protein (10 g), (iii) pea protein (10 g) plus hull fibre (7 g), (iv) yellow peas (406 g), and (v) control. Pea hull fibre and protein were served with tomato sauce and noodles, while yellow peas were served with tomato sauce. Control was noodles and tomato sauce. FI was measured at a pizza meal (135 min). Appetite and BG were measured pre-pizza (0-135 min) and post-pizza (155-215 min). Protein plus fibre and yellow peas led to lower pre-pizza BG area under the curve compared with fibre and control. At 30 min, BG was lower after protein plus fibre and yellow peas compared with fibre and control, whereas at 45 and 75 min, protein plus fibre and yellow peas led to lower BG compared with fibre (p < 0.05). Following the pizza meal (155 min), yellow peas led to lower BG compared with fibre (p < 0.05). No differences were observed in FI or appetite. This trial supports the use of pea components as value-added ingredients in foods designed to improve glycemic control. PMID:25302637

  8. Early maternal separation affects ethanol-induced conditioning in a nor-BNI insensitive manner, but does not alter ethanol-induced locomotor activity.

    PubMed

    Pautassi, Ricardo Marcos; Nizhnikov, Michael E; Fabio, Ma Carolina; Spear, Norman E

    2012-01-01

    Early environmental stress significantly affects the development of offspring. This stress has been modeled in rats through the maternal separation (MS) paradigm, which alters the functioning of the HPA axis and can enhance ethanol intake at adulthood. Infant rats are sensitive to ethanol's reinforcing effects, which modulate ethanol seeking and intake. Little is known about the impact of MS on sensitivity to ethanol's appetitive and aversive effects during infancy. The present study assessed ethanol-induced conditioned place preference established through second-order conditioning (SOC), spontaneous or ethanol-induced locomotor activity and ethanol intake in preweanling rats that experienced normal animal facility rearing (AFR) or daily episodes of maternal separation (MS) during postnatal days 1-13 (PDs 1-13). Low-ethanol dose (0.5 g/kg) induced appetitive conditioned place preference (via SOC) in control rats given conventional rearing but not in rats given maternal separation in early infancy, whereas 2.0 g/kg ethanol induced aversive conditioned place preference in the former but not the latter. The administration of a kappa antagonist at PD 1 or immediately before testing did not alter ethanol-induced reinforcement. High (i.e., 2.5 and 2.0 g/kg) but not low (i.e., 0.5 g/kg) ethanol dose induced reliable motor stimulation, which was independent of early maternal separation. Ethanol intake and blood alcohol levels during conditioning were unaffected by rearing conditions. Pups given early maternal separation had lower body weights than controls and showed an altered pattern of exploration when placed in an open field. These results indicate that, when assessed in infant rats, earlier maternal separation alters the balance between the appetitive and aversive motivational effects of ethanol but has no effect on the motor activating effects of the drug. PMID:22108648

  9. Ethanol Extract of Antrodia camphorata Grown on Germinated Brown Rice Suppresses Inflammatory Responses in Mice with Acute DSS-Induced Colitis

    PubMed Central

    Park, Dong Ki; Park, Hye-Jin

    2013-01-01

    The anti-inflammatory activity of Antrodia camphorata (AC) grown on germinated brown rice (CBR) extract was evaluated in vitro and in vivo. CBR suppressed the release of nitric oxide (NO) and prostaglandin (PG) E2 from lipopolysaccharide-(LPS-)stimulated RAW264.7 cells. CBR inhibited the level of inducible nitric oxide synthase (iNOS) and cyclooxygenase-(COX-)2 proteins, and it activated p38-MAPK, extracellular signal-related kinases (ERK), and NF-κB in LPS-stimulated RAW264.7 macrophages. LPS-induced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA expression was reduced in CBR-treated RAW264.7 cells. In concert with in vitro data, CBR suppressed the levels of dextran-sulfate-sodium-(DSS-)induced iNOS and COX-2 proteins in the colon tissue. CBR treatment inhibited activated p38-MAPK, ERK, and NF-κB proteins in the colon tissue of DSS-induced mice. TNF-α and IL-6 mRNA expression was reduced in DSS+CBR-treated mice. The disease activity index and histological scores were significantly lower in CBR-treated mice (500 mg/kg/day) than in DSS-treated mice (P < 0.05 versus DSS). This is the first report of anti-inflammatory activity of CBR in DSS-induced acute colitis. These results suggest that CBR is a promising, potential agent for preventing acute colitis through the inhibition of NF-κB signaling and its upstream signaling molecules, including MAPKs. PMID:23818935

  10. Ambient temperature effects on taste aversion conditioned by ethanol: contribution of ethanol-induced hypothermia.

    PubMed

    Cunningham, C L; Niehus, J S; Bachtold, J F

    1992-12-01

    Six experiments examined the effects of low (5-10 degrees C), normal (21 degrees C), or high (32 degrees) ambient temperature on conditioned taste aversion and body temperature changes produced by ethanol, lithium chloride, or morphine sulfate. Fluid-deprived rats received five to seven taste conditioning trials at 48-hr intervals. On each trial, access to saccharin at normal ambient temperature was followed by injection of drug or saline and placement for 6 hr into a temperature-controlled enclosure. Exposure to low ambient temperature facilitated, whereas exposure to high ambient temperature retarded acquisition of ethanol-induced conditioned taste aversion. The ability of an alteration in ambient temperature to influence conditioned taste aversion varied as a function of ethanol dose and was related to ambient temperature's effect on ethanol-induced hypothermia. More specifically, strength of conditioned taste aversion was negatively correlated with core body temperature after ethanol injection. Alterations in ambient temperature alone did not affect ingestion of a paired flavor solution in the absence of drug. Moreover, alterations in ambient temperature did not appear to influence conditioned taste aversion by changing ethanol pharmacokinetics. Finally, high and low ambient temperature did not affect development of taste aversion conditioned by lithium chloride or morphine sulfate. The overall pattern of data presented by these experiments supports the hypothesis that ambient-temperature influences strength of ethanol-induced conditioned taste aversion by altering the hypothermic response to ethanol. More generally, these data support the suggestion that body temperature change induced by ethanol is related to ethanol's aversive motivational effects and may be involved in modulating ethanol intake. PMID:1471766

  11. Ethanol sensitivity in rats: effect of prenatal stress.

    PubMed

    DeTurck, K H; Pohorecky, L A

    1987-01-01

    The present study examined whether sensitivity to ethanol could be altered by prenatal stress exposure. Pregnant female rats were handled during the third week of gestation and the offspring were tested for ethanol sensitivity as adults. Compared to control offspring, the following characteristic responses to acute ethanol were significantly attenuated in prenatally stress-exposed rats: the decreases in body temperature, motor coordination and startle amplitude, and the increases in circulating corticosterone and free fatty acids. Ethanol-induced impairment of swim performance, in contrast, was potentiated in these animals. Since no differences were found in blood or breath ethanol levels, the rate of ethanol metabolism was probably not affected by prenatal stress. Rather, the altered responses appear to result from long-term changes in central nervous system sensitivity to ethanol. PMID:3659158

  12. Sub-acute effects of ethanol extract of Sarcocephalus latifolius root on some physiologically important electrolytes in serum of normal Wistar albino rats.

    PubMed

    Enemor, V H A; Okaka, A N C

    2013-12-01

    Sarcocephalus latifolius (Synonym, Nauclea latifolia) is a shrub commonly seen in the South East of Nigeria. It is widely applied as herbal remedy in the treatment of various illnesses. The effect of ethanol extract of the root of the plant on some serum electrolytes was studied. A total of thirty Wistar albino rats were used to determine serum concentrations of K+, Ca2+, Cl- and HCO3-. The animals were divided into six groups of five rats each. Five groups labeled A, B, C, D and E, were administered orally with graded doses of root extract of Sarcocephalus latifolius at concentration of 300, 350, 400, 450 and 500 mg kg(-1) body weight, respectively. The sixth group (Group F) was used as the control and its animals were simply sustained on normal diet and water. Administration of the extract lasted for twenty-one days after which the animals were sacrificed by cardiac puncture. K+, Ca2+, Cl- and HCO3- were determined from each sample and the mean concentration was calculated for each dose and the control. Potassium, calcium and chloride determination were done by colorimetric methods while determination of bicarbonate concentration was done by simple titration. Na+ was separately assayed, by flame photometer, from a set of 18 rats of six animals in each of three groups. For K+, non dose dependent increases were observed which was non-significant (p > 0.05), for A, D and E but significant (p < 0.05) for B and C. Ca2+ showed a dose dependent and significant (p < 0.05) decreases, except for A (p > 0.05). Decreases (p < 0.05) for C, D, E and (p > 0.05) for A and B were observed for Cl-. Serum bicarbonate appeared almost completely unaffected by the extract, showing no significant changes. Na+ levels were depressed for the two test groups, A and B compared with the control (group C), with test group B showing a significant decrease (p < 0.05). From the analysis, it could be concluded that Sarcocephalus latifolius has the capacity to influence various electrolytes to

  13. 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

  14. Acute oral intake of a higenamine-based dietary supplement increases circulating free fatty acids and energy expenditure in human subjects

    PubMed Central

    2013-01-01

    Background Higenamine, also known as norcoclaurine, is an herbal constituent thought to act as a beta-2 adrenergic receptor agonist—possibly stimulating lipolysis. It was the purpose of this study to determine the impact of a higenamine-based dietary supplement on plasma free fatty acids and energy expenditure following acute oral ingestion. Methods Sixteen healthy subjects (8 men; 26.1 ± 2.5 yrs; 8 women 22.4 ± 3.1 yrs) ingested a dietary supplement containing a combination of higenamine, caffeine (270 mg), and yohimbe bark extract or a placebo, on two separate occasions in a double-blind, randomized, cross-over design, separated by 6–8 days. Blood samples were collected immediately before ingestion, and at 30, 60, 120, and 180 minutes post ingestion, and analyzed for plasma free fatty acids (FFA) and glycerol. Breath samples were collected at the same times for a measure of kilocalorie expenditure and respiratory exchange ratio (RER) using indirect calorimetry. Heart rate and blood pressure were recorded at all times. Data collection occurred in the morning following a 10 hour overnight fast. Results A condition effect was noted for both FFA (p < 0.0001) and kilocalorie expenditure (p = 0.001), with values higher for supplement compared to placebo at 60, 120, and 180 minutes post ingestion. No statistically significant effects were noted for glycerol or RER (p > 0.05). A condition effect was noted for heart rate (p = 0.03) and systolic blood pressure (p < 0.0001), with values higher for supplement compared to placebo. Conclusion Ingestion of a higenamine-based dietary supplement stimulates lipolysis and energy expenditure, as evidenced by a significant increase in circulating FFA and kilocalorie expenditure. The same supplement results in a moderate increase in heart rate (~3 bpm) and systolic blood pressure (~12 mmHg), which is consistent with previous studies evaluating moderate doses of caffeine and yohimbine, suggesting that higenamine

  15. Protein Tyrosine Phosphatase α in the Dorsomedial Striatum Promotes Excessive Ethanol-Drinking Behaviors

    PubMed Central

    Ben Hamida, Sami; Darcq, Emmanuel; Wang, Jun; Wu, Su; Phamluong, Khanhky; Kharazia, Viktor

    2013-01-01

    We previously found that excessive ethanol drinking activates Fyn in the dorsomedial striatum (DMS) (Wang et al., 2010; Gibb et al., 2011). Ethanol-mediated Fyn activation in the DMS leads to the phosphorylation of the GluN2B subunit of the NMDA receptor, to the enhancement of the channel's activity, and to the development and/or maintenance of ethanol drinking behaviors (Wang et al., 2007, 2010). Protein tyrosine phosphatase α (PTPα) is essential for Fyn kinase activation (Bhandari et al., 1998), and we showed that ethanol-mediated Fyn activation is facilitated by the recruitment of PTPα to synaptic membranes, the compartment where Fyn resides (Gibb et al., 2011). Here we tested the hypothesis that PTPα in the DMS is part of the Fyn/GluN2B pathway and is thus a major contributor to the neuroadaptations underlying excessive ethanol intake behaviors. We found that RNA interference (RNAi)-mediated PTPα knockdown in the DMS reduces excessive ethanol intake and preference in rodents. Importantly, no alterations in water, saccharine/sucrose, or quinine intake were observed. Furthermore, downregulation of PTPα in the DMS of mice significantly reduces ethanol-mediated Fyn activation, GluN2B phosphorylation, and ethanol withdrawal-induced long-term facilitation of NMDAR activity without altering the intrinsic features of DMS neurons. Together, these results position PTPα upstream of Fyn within the DMS and demonstrate the important contribution of the phosphatase to the maladaptive synaptic changes that lead to excessive ethanol intake. PMID:24005290

  16. Pharmacological characterization of the nociceptin/orphanin FQ receptor on ethanol-mediated motivational effects in infant and adolescent rats.

    PubMed

    Miranda-Morales, Roberto Sebastián; Pautassi, Ricardo M

    2016-02-01

    Activation of nociceptin/orphanin FQ (NOP) receptors attenuates ethanol drinking and prevents relapse in adult rodents. In younger rodents (i.e., infant rats), activation of NOP receptors blocks ethanol-induced locomotor activation but does not attenuate ethanol intake. The aim of the present study was to extend the analysis of NOP modulation of ethanol's effects during early ontogeny. Aversive and anxiolytic effects of ethanol were measured in infant and adolescent rats via conditioned taste aversion and the light-dark box test; whereas ethanol-induced locomotor activity and ethanol intake was measured in adolescents only. Before these tests, infant rats were treated with the natural ligand of NOP receptors, nociceptin (0.0, 0.5 or 1.0 μg) and adolescent rats were treated with the specific agonist Ro 64-6198 (0.0, 0.1 or 0.3 mg/kg). The activation of NOP receptors attenuated ethanol-induced anxiolysis in adolescents only, and had no effect on ethanol's aversive effects. Administration of Ro 64-6198 blocked ethanol-induced locomotor activation but did not modify ethanol intake patterns. The attenuation of ethanol stimulating and anxiolytic effect by activation of NOP receptors indicates a modulatory role of this receptor on ethanol effects, which is expressed early in ontogeny. PMID:25907741

  17. Effect of ganaxolone and THIP on operant and limited-access ethanol self-administration

    PubMed Central

    Ramaker, Marcia J.; Strong, Moriah N.; Ford, Matthew M.; Finn, Deborah A.

    2013-01-01

    Recent evidence suggests that GABAA receptor ligands may regulate ethanol intake via effects at both synaptic and extrasynaptic receptors. For example, the endogenous neurosteroid, allopregnanolone (ALLO) has a similar pharmacological profile as ethanol, and it alters ethanol intake in rodent models. Additionally, recent evidence suggests that δ-subunit containing extrasynaptic GABAA receptors may confer high sensitivity to both ethanol and neurosteroids. The purpose of the present study was to determine the effects of ganaxolone (GAN; an ALLO analogue) and gaboxadol (THIP; a GABAA receptor agonist with selectivity for the extrasynaptic δ-subunit) on ethanol intake, drinking patterns, and bout characteristics in operant and limited access self-administration procedures. In separate studies, the effects of GAN (0 – 10 mg/kg) and THIP (2 – 16 mg/kg) were tested in C57BL/6J male mice provided with two-hour access to a two-bottle choice of water or 10% ethanol or trained to respond for 30 minutes of access to 10% ethanol. GAN had no overall significant effect on operant ethanol self-administration, but tended to decrease the latency to consume the first bout. In the limited-access procedure, GAN dose-dependently decreased ethanol intake. THIP dose-dependently decreased ethanol intake in both paradigms, altering both the consummatory and appetitive processes of operant self-administration as well as shifting the drinking patterns in both procedures. These results add to literature suggesting time-dependent effects of neurosteroids to promote the onset, and to subsequently decrease, ethanol drinking behavior, and they support a role for extrasynaptic GABAA receptor activation in ethanol reinforcement. PMID:22613838

  18. Increased myocardial catalase in rats fed ethanol.

    PubMed Central

    Fahimi, H. D.; Kino, M.; Hicks, L.; Thorp, K. A.; Abelman, W. H.

    1979-01-01

    The effects of chronic intake of dietary ethanol upon catalase, an enzyme capable of metabolizing ethanol, as well as upon myocardial morphology and hemodynamics, were studied in the rat. Ethanol, comprising 36% of dietary calories, administered to rats for 5 weeks, was associated with increased myocardial catalase of 45.9 +/- 3.7 IU/mg protein, compared to 21.0 +/- 1.8 IU/mg protein in pair-fed controls. The enzyme activity remained significantly elevated after 18 weeks of ethanol. Hepatic catalase did not differ in these groups. Parallel cytochemical studies confirmed the increase in myocardial catalase by demonstrating an increase in peroxisomes. Gross and light-microscopic examinations revealed no abnormalities at either 5 or 18 weeks. Remarkably few ultrastructural abnormalities were seen in this material fixed by vascular perfusion. Hemodynamic studies after 5 weeks of ethanol revealed decreased left ventricle systolic pressure and decreased mean arterial pressure but no change in ventricular filling pressure. The possibility of catalase playing a metabolic and potentially protective role in rat myocardium chronically exposed to ethanol is discussed. Images Figure 3 Figure 4-6 Figures 1 and 2 Figures 7 and 8 p[389]-a PMID:474705

  19. Lithium-mediated protection against ethanol neurotoxicity.

    PubMed

    Luo, Jia

    2010-01-01

    Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar) disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action. Ethanol is a neuroteratogen and fetal alcohol spectrum disorders (FASD) are caused by maternal ethanol exposure during pregnancy. FASD is the leading cause of mental retardation. Ethanol exposure causes neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. Excessive alcohol consumption is also associated with Wernicke-Korsakoff syndrome and neurodegeneration in the adult brain. Recent in vivo and in vitro studies indicate that lithium is able to ameliorate ethanol-induced neuroapoptosis. Lithium is an inhibitor of glycogen synthase kinase 3 (GSK3) which has recently been identified as a mediator of ethanol neurotoxicity. Lithium's neuroprotection may be mediated by its inhibition of GSK3. In addition, lithium also affects many other signaling proteins and pathways that regulate neuronal survival and differentiation. This review discusses the recent evidence of lithium-mediated protection against ethanol neurotoxicity and potential underlying mechanisms. PMID:20661453

  20. Preprandial ghrelin is not affected by macronutrient intake, energy intake or energy expenditure

    PubMed Central

    Paul, David R; Kramer, Matthew; Rhodes, Donna G; Rumpler, William V

    2005-01-01

    Background Ghrelin, a peptide secreted by endocrine cells in the gastrointestinal tract, is a hormone purported to have a significant effect on food intake and energy balance in humans. The influence of factors related to energy balance on ghrelin, such as daily energy expenditure, energy intake, and macronutrient intake, have not been reported. Secondly, the effect of ghrelin on food intake has not been quantified under free-living conditions over a prolonged period of time. To investigate these effects, 12 men were provided with an ad libitum cafeteria-style diet for 16 weeks. The macronutrient composition of the diets were covertly modified with drinks containing 2.1 MJ of predominantly carbohydrate (Hi-CHO), protein (Hi-PRO), or fat (Hi-FAT). Total energy expenditure was measured for seven days on two separate occasions (doubly labeled water and physical activity logs). Results Preprandial ghrelin concentrations were not affected by macronutrient intake, energy expenditure or energy intake (all P > 0.05). In turn, daily energy intake was significantly influenced by energy expenditure, but not ghrelin. Conclusion Preprandial ghrelin does not appear to be influenced by macronutrient composition, energy intake, or energy expenditure. Similarly, ghrelin does not appear to affect acute or chronic energy intake under free-living conditions. PMID:15745452

  1. Dopamine D3 Receptor Is Necessary for Ethanol Consumption: An Approach with Buspirone

    PubMed Central

    Leggio, Gian Marco; Camillieri, Giovanni; Platania, Chiara B M; Castorina, Alessandro; Marrazzo, Giuseppina; Torrisi, Sebastiano Alfio; Nona, Christina N; D'Agata, Velia; Nobrega, José; Stark, Holger; Bucolo, Claudio; Le Foll, Bernard; Drago, Filippo; Salomone, Salvatore

    2014-01-01

    Mesolimbic dopamine (DA) controls drug- and alcohol-seeking behavior, but the role of specific DA receptor subtypes is unclear. We tested the hypothesis that D3R gene deletion or the D3R pharmacological blockade inhibits ethanol preference in mice. D3R-deficient mice (D3R−/−) and their wild-type (WT) littermates, treated or not with the D3R antagonists SB277011A and U99194A, were tested in a long-term free choice ethanol-drinking (two-bottle choice) and in a binge-like ethanol-drinking paradigm (drinking in the dark, DID). The selectivity of the D3R antagonists was further assessed by molecular modeling. Ethanol intake was negligible in D3R−/− and robust in WT both in the two-bottle choice and DID paradigms. Treatment with D3R antagonists inhibited ethanol intake in WT but was ineffective in D3R−/− mice. Ethanol intake increased the expression of RACK1 and brain-derived neurotrophic factor (BDNF) in both WT and D3R−/−; in WT there was also a robust overexpression of D3R. Thus, increased expression of D3R associated with activation of RACK1/BDNF seems to operate as a reinforcing mechanism in voluntary ethanol intake. Indeed, blockade of the BDNF pathway by the TrkB selective antagonist ANA-12 reversed chronic stable ethanol intake and strongly decreased the striatal expression of D3R. Finally, we evaluated buspirone, an approved drug for anxiety disorders endowed with D3R antagonist activity (confirmed by molecular modeling analysis), that resulted effective in inhibiting ethanol intake. Thus, DA signaling via D3R is essential for ethanol-related reward and consumption and may represent a novel therapeutic target for weaning. PMID:24584330

  2. Dopamine D3 receptor is necessary for ethanol consumption: an approach with buspirone.

    PubMed

    Leggio, Gian Marco; Camillieri, Giovanni; Platania, Chiara B M; Castorina, Alessandro; Marrazzo, Giuseppina; Torrisi, Sebastiano Alfio; Nona, Christina N; D'Agata, Velia; Nobrega, José; Stark, Holger; Bucolo, Claudio; Le Foll, Bernard; Drago, Filippo; Salomone, Salvatore

    2014-07-01

    Mesolimbic dopamine (DA) controls drug- and alcohol-seeking behavior, but the role of specific DA receptor subtypes is unclear. We tested the hypothesis that D3R gene deletion or the D3R pharmacological blockade inhibits ethanol preference in mice. D3R-deficient mice (D3R(-/-)) and their wild-type (WT) littermates, treated or not with the D3R antagonists SB277011A and U99194A, were tested in a long-term free choice ethanol-drinking (two-bottle choice) and in a binge-like ethanol-drinking paradigm (drinking in the dark, DID). The selectivity of the D3R antagonists was further assessed by molecular modeling. Ethanol intake was negligible in D3R(-/-) and robust in WT both in the two-bottle choice and DID paradigms. Treatment with D3R antagonists inhibited ethanol intake in WT but was ineffective in D3R(-/-) mice. Ethanol intake increased the expression of RACK1 and brain-derived neurotrophic factor (BDNF) in both WT and D3R(-/-); in WT there was also a robust overexpression of D3R. Thus, increased expression of D3R associated with activation of RACK1/BDNF seems to operate as a reinforcing mechanism in voluntary ethanol intake. Indeed, blockade of the BDNF pathway by the TrkB selective antagonist ANA-12 reversed chronic stable ethanol intake and strongly decreased the striatal expression of D3R. Finally, we evaluated buspirone, an approved drug for anxiety disorders endowed with D3R antagonist activity (confirmed by molecular modeling analysis), that resulted effective in inhibiting ethanol intake. Thus, DA signaling via D3R is essential for ethanol-related reward and consumption and may represent a novel therapeutic target for weaning. PMID:24584330

  3. Ethanol promotes T cell apoptosis through the mitochondrial pathway

    PubMed Central

    Kapasi, Aditi A; Patel, Geeta; Goenka, Anuj; Nahar, Nilay; Modi, Neeraj; Bhaskaran, Madhu; Reddy, Krishna; Franki, Nicholas; Patel, Jaimita; Singhal, Pravin C

    2003-01-01

    Clinical reports suggest that acute ethanol intoxication is often associated with lymphopenia. Previously, ethanol was reported to invoke thymocyte apoptosis. We studied the effect of ethanol on T cell apoptosis. In addition, we evaluated the molecular mechanism of ethanol-induced T cell apoptosis. Human T cells harvested from healthy subjects after an alcohol drinking binge showed enhanced T cell apoptosis (before, 0·4 ± 0·2% versus after, 19·6 ± 2·5% apoptotic lymphocytes/field; P < 0·001). In in vitro studies, ethanol in a concentration of 50 mm and higher enhanced the apoptosis of Jurkat cells. DNA isolated from ethanol-treated Jurkat cells displayed integer multiples of 180 base pairs. Ethanol decreased Jurkat cell expression of Bcl-2, whereas ethanol increased Jurkat cell expression of Bax. Jurkat cells treated with ethanol also showed translocation of cytochrome C into cytosol. Moreover, a caspase-9 inhibitor partially inhibited ethanol-induced Jurkat cell apoptosis. In in vivo studies, after binge drinking, T cell expression of Bcl-2 also decreased. In addition, binge drinking induced the cleavage of caspase-3, suggesting activation of caspase-3 in T cells. These results suggest that ethanol promotes T cell apoptosis through the activation of intrinsic or mitochondrial pathway. PMID:12603597

  4. Stress history increases alcohol intake in relapse: Relation to phosphodiesterase 10A

    PubMed Central

    Logrip, Marian L.; Zorrilla, Eric P.

    2012-01-01

    Stressful experiences in humans can result in elevated alcohol drinking, as exemplified in many individuals with post-traumatic stress disorder. However, how stress history, rather than acute stressors, influences alcohol intake remains uncertain. To model the protracted effects of past stress, male Wistar rats were subjected to light-cued footshock stress (Stress History) or light cues alone (Control) prior to their acquisition of alcohol self-administration (1-h sessions, fixed ratio1–3, 100 µl of 10% v/v alcohol as reinforcer). Stress history did not alter mean alcohol intake during acquisition of self-administration, but it increased preference for the alcohol-paired lever over the inactive lever. Following an extinction period, rats with a history of stress exposure and low baseline alcohol intake showed a 2-fold elevation in alcohol self-administration, as compared to low-drinking rats with no stress history. Similar effects were not seen in rats self-administering 0.1% sucrose. Analysis of mRNA levels of phosphodiesterase 10A (PDE10A), a dual-specificity cAMP and cGMP hydrolyzing enzyme, showed that stress history increased Pde10a mRNA levels in the basolateral amygdala and, in low drinking rats, the prelimbic prefrontal cortex (plPFC). Pde10a mRNA levels in the plPFC correlated directly with greater alcohol self-administration during the relapse-like phase, and greater BLA Pde10a mRNA levels correlated with increased ethanol preference after acquisition. The data demonstrate that stress history sensitizes otherwise low alcohol drinkers to consume more alcohol in a relapse-like situation, and identify stress-induced neuroadaptations in amygdala and prefrontal cortical Pde10a expression as changes that may drive heightened alcohol intake and preference in susceptible individuals. PMID:22741603

  5. Ontogenetic differences in ethanol's motivational properties during infancy.

    PubMed

    Nizhnikov, Michael E; Pautassi, Ricardo Marcos; Varlinskaya, Elena I; Rahmani, Pouyan; Spear, Norman E

    2012-05-01

    Pairing a conditioned stimulus (CS) with ethanol generally produces aversion for that CS in adult rodents. However, infant rats (PD1-PD3) exposed to ethanol demonstrate appetitive reinforcement to ethanol (Nizhnikov, Varlinskaya, Petrov, & Spear, 2006; Petrov, Varlinskaya, & Spear, 2003). This sensitivity to the appetitive properties of ethanol during infancy may be transient, as during the second postnatal week rat pups tend to exhibit conditioned aversions to flavors paired with ethanol. The present study examined changes in the motivation properties of ethanol through ontogeny and the neurobiology underlying these changes. Rat pups were exposed to a taste conditioning procedure on PD4 or PD12. Rat pups were intraorally infused with 2.5% of their body weight of saccharin solution (0.1%) and immediately after injected intraperitoneolly (i.p.) with one of six doses of ethanol (0.0-2.0 g/kg). A day later pups were given saccharine infusions and percent body weight gain was used as an index of ethanol's reinforcing effects. PD4 pups expressed appetitive reinforcement to ethanol, as indicated by greater saccharin intake, as compared to control counterparts and to the older PD12 pups. Subsequent experiments revealed that PD4 pups were less sensitive to the aversive properties of the drug than PD12 pups. The older pups found high doses of ethanol aversive while PD4 rat pups did not condition aversions to this dose of ethanol after a single trial. A similar pattern of results was observed between the low doses of ethanol and the highest doses of a kappa opioid agonist. The PD12 animals did not condition to the kappa opioid agonist, while the younger rats expressed an appetitive response. These results illustrate an ontogenetic change in the motivational properties of ethanol, with sensitivity to its appetitive properties declining and responsiveness to the aversive properties increasing with age during early infancy. PMID:22440692

  6. Schedule-induced Polydipsia in Lines of Rats Selectively Bred for High and Low Ethanol Preference

    PubMed Central

    Gilpin, N. W.; Badia-Elder, N. E.; Elder, R. L.; Stewart, R. B.

    2008-01-01

    Ethanol drinking was assessed in the P/NP, HAD1/LAD1, and HAD2/LAD2 lines of rats under environmental conditions that produce schedule-induced polydipsia. Female rats (n = 8/line), maintained at 85% of free-feeding body weights, underwent daily 1-h sessions during which 45-mg food pellets were delivered every 60 s. Water, 2, 4, 8, 16, or 32% w/v ethanol solution was available from a single bottle for 8 consecutive sessions at each concentration, with blood-ethanol levels (BELs) determined after selected sessions. P and HAD2 rats drank more water and ethanol than their non-preferring counterparts, while HAD1 and LAD1 rats did not differ. Ethanol intake and BELs were positively correlated (r = 0.75) across lines. Finally, rats were allowed 14 daily choice sessions with 8% ethanol and water concurrently available. Water intake generally exceeded ethanol intake in all lines, while P rats drank similar amounts of both fluids. These line differences indicate pleiotropic effects of genes that mediate ethanol intake and schedule-induced behaviors. PMID:18780177

  7. MOLECULAR TARGETS AND MECHANISMS FOR ETHANOL ACTION IN GLYCINE RECEPTORS

    PubMed Central

    Perkins, Daya I.; Trudell, James R.; Crawford, Daniel K.; Alkana, Ronald L.; Davies, Daryl L.

    2010-01-01

    Glycine receptors (GlyRs) are recognized as the primary mediators of neuronal inhibition in the spinal cord, brain stem and higher brain regions known to be sensitive to ethanol. Building evidence supports the notion that ethanol acting on GlyRs causes at least a subset of its behavioral effects and may be involved in modulating ethanol intake. For over two decades, GlyRs have been studied at the molecular level as targets for ethanol action. Despite the advances in understanding the effects of ethanol in vivo and in vitro, the precise molecular sites and mechanisms of action for ethanol in ligand-gated ion channels in general, and in GlyRs specifically, are just now starting to become understood. The present review focuses on advances in our knowledge produced by using molecular biology, pressure antagonism, electrophysiology and molecular modeling strategies over the last two decades to probe, identify and model the initial molecular sites and mechanisms of ethanol action in GlyRs. The molecular targets on the GlyR are covered on a global perspective, which includes the intracellular, transmembrane and extracellular domains. The latter has received increasing attention in recent years. Recent molecular models of the sites of ethanol action in GlyRs and their implications to our understanding of possible mechanism of ethanol action and novel targets for drug development in GlyRs are discussed. PMID:20399807

  8. Ethanol Basics (Fact Sheet)

    SciTech Connect

    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.

  9. KCNQ channels show conserved ethanol block and function in ethanol behaviour.

    PubMed

    Cavaliere, Sonia; Gillespie, John M; Hodge, James J L

    2012-01-01

    In humans, KCNQ2/3 channels form an M-current that regulates neuronal excitability, with mutations in these channels causing benign neonatal familial convulsions. The M-current is important in mechanisms of neural plasticity underlying associative memory and in the response to ethanol, with KCNQ controlling the release of dopamine after ethanol exposure. We show that dKCNQ is broadly expressed in the nervous system, with targeted reduction in neuronal KCNQ increasing neural excitability and KCNQ overexpression decreasing excitability and calcium signalling, consistent with KCNQ regulating the resting membrane potential and neural release as in mammalian neurons. We show that the single KCNQ channel in Drosophila (dKCNQ) has similar electrophysiological properties to neuronal KCNQ2/3, including conserved acute sensitivity to ethanol block, with the fly channel (IC(50) = 19.8 mM) being more sensitive than its mammalian ortholog (IC(50) = 42.1 mM). This suggests that the role of KCNQ in alcohol behaviour can be determined for the first time by using Drosophila. We present evidence that loss of KCNQ function in Drosophila increased sensitivity and tolerance to the sedative effects of ethanol. Acute activation of dopaminergic neurons by heat-activated TRP channel or KCNQ-RNAi expression produced ethanol hypersensitivity, suggesting that both act via a common mechanism involving membrane depolarisation and increased dopamine signalling leading to ethanol sedation. PMID:23209695

  10. Inhalation delivery of proteins from ethanol suspensions.

    PubMed

    Choi, W S; Murthy, G G; Edwards, D A; Langer, R; Klibanov, A M

    2001-09-25

    To circumvent inherent problems associated with pulmonary administration of aqueous-solution and dry-powder protein drugs, inhalation delivery of proteins from their suspensions in absolute ethanol was explored both in vitro and in vivo. Protein suspensions in ethanol of up to 9% (wt/vol) were readily aerosolized with a commercial compressor nebulizer. Experiments with enzymic proteins revealed that nebulization caused no detectable loss of catalytic activity; furthermore, enzyme suspensions in anhydrous ethanol retained their full catalytic activity for at least 3 weeks at room temperature. With the use of Zn(2+)-insulin, conditions were elaborated that produced submicron protein particles in ethanol suspensions. The latter (insulin/EtOH) afforded respirable-size aerosol particles after nebulization. A 40-min exposure of laboratory rats to 10 mg/ml insulin/EtOH aerosols resulted in a 2-fold drop in the blood glucose level and a marked rise in the serum insulin level. The bioavailability based on estimated deposited lung dose of insulin delivered by inhalation of ethanol suspension aerosols was 33% (relative to an equivalent s.c. injection), i.e., comparable to those observed in rats after inhalation administration of dry powder and aqueous solutions of insulin. Inhalation of ethanol in a relevant amount/time frame resulted in no detectable acute toxic effects on rat lungs or airways, as reflected by the absence of statistically significant inflammatory or allergic responses, damage to the alveolar/capillary barrier, and lysed and/or damaged cells. PMID:11562495

  11. Individual differences in voluntary ethanol consumption lead to differential activation of the central amygdala in rats: relationship to the anxiolytic and stimulant effects of low dose ethanol

    PubMed Central

    Sharko, Amanda C.; Kaigler, Kris F.; Fadel, Jim R.; Wilson, Marlene A.

    2016-01-01

    Background Although alcohol use disorders and anxiety disorders are highly comorbid, the relationship between these two disorders is not fully understood. Previous work from our laboratory shows that anxiety-like behavior is highly variable in outbred Long-Evans rats and is related to the level of voluntary ethanol consumption, suggesting that basal anxiety state influences ethanol intake. To further examine the relationship between the acquisition of ethanol consumption and anxiety phenotype, Long-Evans rats were assessed for anxiety-like behavior and neuronal activation following voluntary ethanol consumption in a limited access drinking paradigm. Methods Rats were allowed to self-administer ethanol (6%v/v) for four days using a limited access drinking in the dark (DID) paradigm and divided into high and low drinking groups based on a median split of average daily ethanol intake. Immediately following the fourth drinking session, animals were tested on the elevated plus maze and evaluated for anxiety-like behaviors. Fos immunoreactivity was assessed in the central and basolateral amygdala, as well as the bed nucleus of the stria terminalis. Results High ethanol drinkers spent significantly more time on the open arms of the plus maze than low ethanol drinkers. High ethanol drinkers also had increased locomotor activity as compared to both low ethanol drinkers and water drinkers. Fos immunoreactivity was positively correlated with ethanol consumption in all brain regions examined, although Fos positive cell counts were only significantly different between high and low ethanol drinkers in the central amygdala. Conclusions Our findings demonstrate that outbred rats will voluntarily consume behaviorally effective doses of ethanol in a short-term access model and ethanol consumption is positively correlated with increased neuronal activation in the central amygdala. PMID:22834974

  12. A crucial role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through Inhibition of Wnt / Beta-catenin Signaling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mechanisms by which chronic ethanol intake induces bone loss remain largely unclear. Especially in females, skeletal response to ethanol may vary depending on the physiologic status (viz. cycling, pregnancy, lactation). Nonetheless, ethanol-induced oxidative stress appears to be the key event le...

  13. A role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of wnt/beta-catenin signaling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mechanisms by which chronic ethanol intake induces bone loss remain unclear. In females, the skeletal response to ethanol varies depending on physiologic status (viz. cycling, pregnancy, lactation). Ethanol-induced oxidative stress appears to be a key event leading to skeletal toxicity. In the c...

  14. Using drinking in the dark to model prenatal binge-like exposure to ethanol in C57BL/6J mice.

    PubMed

    Boehm, Stephen L; Moore, Eileen M; Walsh, Cherie D; Gross, Carly D; Cavelli, Austin M; Gigante, Eduardo; Linsenbardt, David N

    2008-09-01

    Animal models of prenatal ethanol exposure are necessary to more fully understand the effects of ethanol on the developing embryo/fetus. However, most models employ procedures that may produce additional maternal stress beyond that produced by ethanol alone. We employed a daily limited-access ethanol intake model called Drinking in the Dark (DID) to assess the effects of voluntary maternal binge-like ethanol intake on the developing mouse. Evidence suggests that binge exposure may be particularly harmful to the embryo/fetus, perhaps due to the relatively higher blood ethanol concentrations achieved. Pregnant females had mean daily ethanol intakes ranging from 4.2 to 6.4 g/kg ethanol over gestation, producing blood ethanol concentrations ranging from 115 to 182 mg/dL. This level of ethanol intake produced behavioral alterations among adolescent offspring that disappeared by adulthood, including altered sensitivity to ethanol's hypnotic actions. The DID model may provide a useful tool for studying the effects of prenatal ethanol exposure in mice. PMID:18683190

  15. Autophagy and ethanol neurotoxicity

    PubMed Central

    Luo, Jia

    2015-01-01

    Excessive ethanol exposure is detrimental to the brain. The developing brain is particularly vulnerable to ethanol such that prenatal ethanol exposure causes fetal alcohol spectrum disorders (FASD). Neuronal loss in the brain is the most devastating consequence and is associated with mental retardation and other behavioral deficits observed in FASD. Since alcohol consumption during pregnancy has not declined, it is imperative to elucidate the underlying mechanisms and develop effective therapeutic strategies. One cellular mechanism that acts as a protective response for the central nervous system (CNS) is autophagy. Autophagy regulates lysosomal turnover of organelles and proteins within cells, and is involved in cell differentiation, survival, metabolism, and immunity. We have recently shown that ethanol activates autophagy in the developing brain. The autophagic preconditioning alleviates ethanol-induced neuron apoptosis, whereas inhibition of autophagy potentiates ethanol-stimulated reactive oxygen species (ROS) and exacerbates ethanol-induced neuroapoptosis. The expression of genes encoding proteins required for autophagy in the CNS is developmentally regulated; their levels are much lower during an ethanol-sensitive period than during an ethanol-resistant period. Ethanol may stimulate autophagy through multiple mechanisms; these include induction of oxidative stress and endoplasmic reticulum stress, modulation of MTOR and AMPK signaling, alterations in BCL2 family proteins, and disruption of intracellular calcium (Ca2+) homeostasis. This review discusses the most recent evidence regarding the involvement of autophagy in ethanol-mediated neurotoxicity as well as the potential therapeutic approach of targeting autophagic pathways. PMID:25484085

  16. Effects of ethanol on cAMP production in murine embryonic palate mesenchymal cells

    SciTech Connect

    Weston, W.M.; Greene, R.M. )

    1991-01-01

    Ethanol affected the ability of murine embryonic palate mesenchymal (MEPM) cells to produce cAMP in response to hormone treatment. Acute exposure to ethanol resulted in an increase in hormone-stimulated cAMP levels, while chronic ethanol treatment led to decreased sensitivity to hormone. Forskolin-stimulated cAMP levels were decreased by both acute and chronic ethanol treatment, while the cells' response to cholera toxin was unchanged by ethanol treatment. The lack of sensitivity of the cholera toxin response to ethanol suggests that,in contrast to what has been observed in other systems, ethanol does not affect the production or activity of G{alpha}s in MEPM cells. These results suggest a possible explanation for the molecular basis for the craniofacial abnormalities observed in the fetal alcohol syndrome.

  17. Orexin-1 and orexin-2 receptor antagonists reduce ethanol self-administration in high-drinking rodent models.

    PubMed

    Anderson, Rachel I; Becker, Howard C; Adams, Benjamin L; Jesudason, Cynthia D; Rorick-Kehn, Linda M

    2014-01-01

    To examine the role of orexin-1 and orexin-2 receptor activity on ethanol self-administration, compounds that differentially target orexin (OX) receptor subtypes were assessed in various self-administration paradigms using high-drinking rodent models. Effects of the OX1 antagonist SB334867, the OX2 antagonist LSN2424100, and the mixed OX1/2 antagonist almorexant (ACT-078573) on home cage ethanol consumption were tested in ethanol-preferring (P) rats using a 2-bottle choice procedure. In separate experiments, effects of SB334867, LSN2424100, and almorexant on operant ethanol self-administration were assessed in P rats maintained on a progressive ratio operant schedule of reinforcement. In a third series of experiments, SB334867, LSN2424100, and almorexant were administered to ethanol-preferring C57BL/6J mice to examine effects of OX receptor blockade on ethanol intake in a binge-like drinking (drinking-in-the-dark) model. In P rats with chronic home cage free-choice ethanol access, SB334867 and almorexant significantly reduced ethanol intake, but almorexant also reduced water intake, suggesting non-specific effects on consummatory behavior. In the progressive ratio operant experiments, LSN2424100 and almorexant reduced breakpoints and ethanol consumption in P rats, whereas the almorexant inactive enantiomer and SB334867 did not significantly affect the motivation to consume ethanol. As expected, vehicle-injected mice exhibited binge-like drinking patterns in the drinking-in-the-dark model. All three OX antagonists reduced both ethanol intake and resulting blood ethanol concentrations relative to vehicle-injected controls, but SB334867 and LSN2424100 also reduced sucrose consumption in a different cohort of mice, suggesting non-specific effects. Collectively, these results contribute to a growing body of evidence indicating that OX1 and OX2 receptor activity influences ethanol self-administration, although the effects may not be selective for ethanol consumption

  18. Orexin-1 and orexin-2 receptor antagonists reduce ethanol self-administration in high-drinking rodent models

    PubMed Central

    Anderson, Rachel I.; Becker, Howard C.; Adams, Benjamin L.; Jesudason, Cynthia D.; Rorick-Kehn, Linda M.

    2014-01-01

    To examine the role of orexin-1 and orexin-2 receptor activity on ethanol self-administration, compounds that differentially target orexin (OX) receptor subtypes were assessed in various self-administration paradigms using high-drinking rodent models. Effects of the OX1 antagonist SB334867, the OX2 antagonist LSN2424100, and the mixed OX1/2 antagonist almorexant (ACT-078573) on home cage ethanol consumption were tested in ethanol-preferring (P) rats using a 2-bottle choice procedure. In separate experiments, effects of SB334867, LSN2424100, and almorexant on operant ethanol self-administration were assessed in P rats maintained on a progressive ratio operant schedule of reinforcement. In a third series of experiments, SB334867, LSN2424100, and almorexant were administered to ethanol-preferring C57BL/6J mice to examine effects of OX receptor blockade on ethanol intake in a binge-like drinking (drinking-in-the-dark) model. In P rats with chronic home cage free-choice ethanol access, SB334867 and almorexant significantly reduced ethanol intake, but almorexant also reduced water intake, suggesting non-specific effects on consummatory behavior. In the progressive ratio operant experiments, LSN2424100 and almorexant reduced breakpoints and ethanol consumption in P rats, whereas the almorexant inactive enantiomer and SB334867 did not significantly affect the motivation to consume ethanol. As expected, vehicle-injected mice exhibited binge-like drinking patterns in the drinking-in-the-dark model. All three OX antagonists reduced both ethanol intake and resulting blood ethanol concentrations relative to vehicle-injected controls, but SB334867 and LSN2424100 also reduced sucrose consumption in a different cohort of mice, suggesting non-specific effects. Collectively, these results contribute to a growing body of evidence indicating that OX1 and OX2 receptor activity influences ethanol self-administration, although the effects may not be selective for ethanol consumption

  19. 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. PMID:25267448

  20. Ethanol consumption in mice: relationships with circadian period and entrainment

    PubMed Central

    Trujillo, Jennifer L.; Do, David T.; Grahame, Nicholas J.; Roberts, Amanda J.; Gorman, Michael R.

    2011-01-01

    A functional connection between the circadian timing system and alcohol consumption is suggested by multiple lines of converging evidence. Ethanol consumption perturbs physiological rhythms in hormone secretion, sleep and body temperature, and conversely, genetic and environmental perturbations of the circadian system can alter alcohol intake. A fundamental property of the circadian pacemaker, the endogenous period of its cycle under free-running conditions, was previously shown to differ between selectively bred High- (HAP) and Low- (LAP) Alcohol Preferring replicate 1 mice. To test whether there is a causal relationship between circadian period and ethanol intake, we induced experimental, rather than genetic, variations in free-running period. Male inbred C57Bl/6J mice and replicate 2 male and female HAP2 and LAP2 mice were entrained to light:dark cycles of 26 h or 22 h or remained in a standard 24 h cycle. Upon discontinuation of the light:dark cycle, experimental animals exhibited longer and shorter free-running periods, respectively. Despite robust effects on circadian period and clear circadian rhythms in drinking, these manipulations failed to alter the daily ethanol intake of the inbred strain or selected lines. Likewise, driving the circadian system at long and short periods produced no change in alcohol intake. In contrast with replicate 1 HAP and LAP lines, there was no difference in free-running period between ethanol naïve HAP2 and LAP2 mice. HAP2 mice, however, were significantly more active than LAP2 mice as measured by general home-cage movement and wheel running, a motivated behavior implicating a selection effect on reward systems. Despite a marked circadian regulation of drinking behavior, the free-running and entrained period of the circadian clock does not determine daily ethanol intake. PMID:20880659

  1. Ethanol consumption in mice: relationships with circadian period and entrainment.

    PubMed

    Trujillo, Jennifer L; Do, David T; Grahame, Nicholas J; Roberts, Amanda J; Gorman, Michael R

    2011-03-01

    A functional connection between the circadian timing system and alcohol consumption is suggested by multiple lines of converging evidence. Ethanol consumption perturbs physiological rhythms in hormone secretion, sleep, and body temperature; and conversely, genetic and environmental perturbations of the circadian system can alter alcohol intake. A fundamental property of the circadian pacemaker, the endogenous period of its cycle under free-running conditions, was previously shown to differ between selectively bred high- (HAP) and low- (LAP) alcohol preferring replicate 1 mice. To test whether there is a causal relationship between circadian period and ethanol intake, we induced experimental, rather than genetic, variations in free-running period. Male inbred C57Bl/6J mice and replicate 2 male and female HAP2 and LAP2 mice were entrained to light:dark cycles of 26 or 22 h or remained in a standard 24 h cycle. On discontinuation of the light:dark cycle, experimental animals exhibited longer and shorter free-running periods, respectively. Despite robust effects on circadian period and clear circadian rhythms in drinking, these manipulations failed to alter the daily ethanol intake of the inbred strain or selected lines. Likewise, driving the circadian system at long and short periods produced no change in alcohol intake. In contrast with replicate 1 HAP and LAP lines, there was no difference in free-running period between ethanol naïve HAP2 and LAP2 mice. HAP2 mice, however, were significantly more active than LAP2 mice as measured by general home-cage movement and wheel running, a motivated behavior implicating a selection effect on reward systems. Despite a marked circadian regulation of drinking behavior, the free-running and entrained period of the circadian clock does not determine daily ethanol intake. PMID:20880659

  2. Maternal care alterations induced by repeated ethanol leads to heightened consumption of the drug and motor impairment during adolescence: a dose-response analysis.

    PubMed

    Ponce, Luciano F; Pautassi, Ricardo Marcos; Spear, Norman E; Molina, Juan C

    2011-07-01

    Maternal ethanol exposure during lactation induces behavioral alterations in offspring, including disruptions in motor skills and heightened ethanol ingestion during adolescence. These behavioral outcomes appear to partially depend on ethanol-induced disruptions in maternal care. The present study assessed motor skills and ethanol intake in adolescent rats raised by dams that had been repeatedly given ethanol during lactation. Female rats (postpartum days [PDs] 3-13) were administered ethanol (0.5, 1.5, or 2.5 g/kg) or vehicle every other day and allowed to freely interact with their pups. During adolescence, the offspring were evaluated for motor coordination (accelerating rotarod test) and oral ethanol self administration. The lowest maternal ethanol dose (0.5 g/kg) mildly affected motor performance, whereas the higher doses (1.5 and 2.5 g/kg) resulted in motor coordination impairment and greater ethanol intake. Maternal care behavior was affected by ethanol in a dose-dependent fashion. These results indicate that early experience with ethanol during lactation, even when the drug dosage is kept relatively low, leads to long-term consequences in offspring. Dose-response effects on maternal care behavior (i.e., nest building, crouching) may underlie disruptions in motor development and greater ethanol intake resulting from these early ethanol experiences. PMID:21334354

  3. GIRK3 gates activation of the mesolimbic dopaminergic pathway by ethanol

    PubMed Central

    Herman, Melissa A.; Sidhu, Harpreet; Stouffer, David G.; Kreifeldt, Max; Le, David; Cates-Gatto, Chelsea; Munoz, Michaelanne B.; Roberts, Amanda J.; Parsons, Loren H.; Roberto, Marisa; Wickman, Kevin; Slesinger, Paul A.; Contet, Candice

    2015-01-01

    G protein-gated inwardly rectifying potassium (GIRK) channels are critical regulators of neuronal excitability and can be directly activated by ethanol. Constitutive deletion of the GIRK3 subunit has minimal phenotypic consequences, except in response to drugs of abuse. Here we investigated how the GIRK3 subunit contributes to the cellular and behavioral effects of ethanol, as well as to voluntary ethanol consumption. We found that constitutive deletion of GIRK3 in knockout (KO) mice selectively increased ethanol binge-like drinking, without affecting ethanol metabolism, sensitivity to ethanol intoxication, or continuous-access drinking. Virally mediated expression of GIRK3 in the ventral tegmental area (VTA) reversed the phenotype of GIRK3 KO mice and further decreased the intake of their wild-type counterparts. In addition, GIRK3 KO mice showed a blunted response of the mesolimbic dopaminergic (DA) pathway to ethanol, as assessed by ethanol-induced excitation of VTA neurons and DA release in the nucleus accumbens. These findings support the notion that the subunit composition of VTA GIRK channels is a critical determinant of DA neuron sensitivity to drugs of abuse. Furthermore, our study reveals the behavioral impact of this cellular effect, whereby the level of GIRK3 expression in the VTA tunes ethanol intake under binge-type conditions: the more GIRK3, the less ethanol drinking. PMID:25964320

  4. Influence of maternal ethanol ingestion on copper utilization during gestation and lactation in the rat

    SciTech Connect

    Baek, J.H.; Cerklewski, F.L.

    1986-03-05

    A factorial experiment was conducted to determine the influence of ethanol intake (30% of Kcal) on the utilization of copper (Cu) at two dietary levels of Cu during gestation and lactation in the rat. Cu levels in the liquid diet were adjusted to provide either 60% of the minimum requirement or a more than adequate intake. Both ethanol and low Cu depressed dam liver Cu, but the lowest concentration was produced when ethanol and low Cu were combined. Although only ethanol depressed pup liver Cu concentration, the effects observed in dams were reflected in pup Cu content of the metallothionein fraction eluted from a Sephadex G-75 column. Otherwise, neither the metallothionein content of maternal intestinal cells nor that of pup liver affected the outcome of ethanol-antagonized Cu utilization. Effects of ethanol on Cu status of dams and pups cannot be defined as a simple C deficiency even though liver iron was elevated because the ferroxidase activity of dam ceruloplasmin was enhanced rather than inhibited by ethanol which is in agreement with observations made in alcoholics. The authors results are more consistent with a possible enhancing effect of ethanol on biliary excretion of Cu. Exactly why ethanol would have this effect in dams is not defined by available data. In pups, however, maternal ethanol ingestion caused a 30% increase in pup plasma corticosterone, a steroid known to enhance loss of neonatal liver Cu by way of biliary excretion.

  5. T1r3 taste receptor involvement in gustatory neural responses to ethanol and oral ethanol preference

    PubMed Central

    Norman, Meghan B.; Lemon, Christian H.

    2010-01-01

    Elevated alcohol consumption is associated with enhanced preference for sweet substances across species and may be mediated by oral alcohol-induced activation of neurobiological substrates for sweet taste. Here, we directly examined the contribution of the T1r3 receptor protein, important for sweet taste detection in mammals, to ethanol intake and preference and the neural processing of ethanol taste by measuring behavioral and central neurophysiological responses to oral alcohol in T1r3 receptor-deficient mice and their C57BL/6J background strain. T1r3 knockout and wild-type mice were tested in behavioral preference assays for long-term voluntary intake of a broad concentration range of ethanol, sucrose, and quinine. For neurophysiological experiments, separate groups of mice of each genotype were anesthetized, and taste responses to ethanol and stimuli of different taste qualities were electrophysiologically recorded from gustatory neurons in the nucleus of the solitary tract. Mice lacking the T1r3 receptor were behaviorally indifferent to alcohol (i.e., ∼50% preference values) at concentrations typically preferred by wild-type mice (5–15%). Central neural taste responses to ethanol in T1r3-deficient mice were significantly lower compared with C57BL/6J controls, a strain for which oral ethanol stimulation produced a concentration-dependent activation of sweet-responsive NTS gustatory neurons. An attenuated difference in ethanol preference between knockouts and controls at concentrations >15% indicated that other sensory and/or postingestive effects of ethanol compete with sweet taste input at high concentrations. As expected, T1r3 knockouts exhibited strongly suppressed behavioral and neural taste responses to sweeteners but did not differ from wild-type mice in responses to prototypic salt, acid, or bitter stimuli. These data implicate the T1r3 receptor in the sensory detection and transduction of ethanol taste. PMID:20145204

  6. Evaluation of the ethanol antagonist' Ro15-4513 on cardiovascular and metabolic responses induced by ethanol

    SciTech Connect

    Lerner, M.R.; Gauvin, D.V.; Holloway, F.A.; Wilson, M.F.; Brackett, D.J. Veterans Affairs Medical Center, Oklahoma City, OK )

    1992-02-26

    The putative ethanol antagonist Ro15-4513 has been reported to attenuate many behavioral responses induced by ethanol, including motor coordination, narcosis, ethanol self administration and intake, and anticonvulsant actions. This study was designed to study the effect of Ro15-4513 on cardiovascular and metabolic responses elicited by intragastric ethanol in conscious rats. Four groups of rats were catheterized under enflurane anesthesia and allowed to regain consciousness. Each group was given either 3.2, 10.0, or 32.0 mg/kg Ro15-4513 or equivalent Tween (i.p.) following ethanol. Ro15-4513 had no effect at any concentration on the decreases in mean arterial pressure, cardiac output, central venous pressure, respiration rate, and cardiac stroke volume and the increases in systemic vascular resistance, heart rate, and glucose evoked by the ethanol challenge. Blood alcohol concentrations measured throughout the study were not affected by any concentration of Ro15-4513. These data suggest that even though Ro15-4513 has significant effects on behavioral responses induced by ethanol it has no effect on the cardiovascular and metabolic responses elicited during ethanol intoxication.

  7. The histone deacetylase (HDAC) inhibitor valproic acid reduces ethanol consumption and ethanol-conditioned place preference in rats.

    PubMed

    Al Ameri, Mouza; Al Mansouri, Shamma; Al Maamari, Alyazia; Bahi, Amine

    2014-10-01

    Recent evidence suggests that epigenetic mechanisms such as chromatin modification (specifically histone acetylation) may play a crucial role in the development of addictive behavior. However, little is known about the role of epigenetic modifications in the rewarding properties of ethanol. In the current study, we studied the effects of systemic injection of the histone deacetylase (HDAC) inhibitor, valproic acid (VPA) on ethanol consumption and ethanol-elicited conditioned place preference (CPP). The effect of VPA (300 mg/kg) on voluntary ethanol intake and preference was assessed using continuous two-bottle choice procedure with escalating concentrations of alcohol (2.5-20% v/v escalating over 4 weeks). Taste sensitivity was studies using saccharin (sweet; 0.03% and 0.06%) and quinine (bitter; 20 µM and 40 µM) tastants solutions. Ethanol conditioned reward was investigated using an unbiased CPP model. Blood ethanol concentration (BEC) was also measured. Compared to vehicle, VPA-injected rats displayed significantly lower preference and consumption of ethanol in a two-bottle choice paradigm, with no significant difference observed with saccharin and quinine. More importantly, 0.5 g/kg ethanol-induced-CPP acquisition was blocked following VPA administration. Finally, vehicle- and VPA-treated mice had similar BECs. Taken together, our results implicated HDAC inhibition in the behavioral and reinforcement-related effects of alcohol and raise the question of whether specific drugs that target HDAC could potentially help to tackle alcoholism in humans. PMID:25108044

  8. Effects of number of cagemates on home cage ethanol drinking during proximal cagemate drinking (PCD) procedures in male and female CD-1 mice.

    PubMed

    Tomie, Arthur; Samuel, Allison Gayle; Sprung, Dana Michelle; Malul, Yael; Yu, Lei

    2015-03-01

    The present experiment evaluated the effects of the Number of Cagemates (0 vs 1 vs 2) on home cage ethanol drinking during Proximal Cagemate Drinking (PCD) procedures in Male and Female CD-1 mice. Continuous-access home cage 2-bottle (ethanol vs. water) free-choice procedures were employed. PCD procedures eliminate the distracting effects of direct physical contact between Drinkers and their Cagemates on ethanol drinking by imposing a translucent plastic barrier strip between them. If direct physical contact distracts from drinking, then one Cagemate would drink more ethanol and more water than two Cagemates housed together on the same side of the barrier. This would be the case even if two Cagemates stimulated more ethanol drinking in the Drinker housed on the other side of the barrier, due to the social stimulation effects of additional Cagemates. Results revealed that the ethanol intake of Female Drinkers was directly related to the number of Cagemates on the other side of the barrier strip, but this social stimulation effect was not observed in Male Drinkers. For Male Cagemates and Female Cagemates, the single Cagemate provided elevated ethanol intake and elevated water intake relative to the ethanol intake and water intake of each Cagemate in the two Cagemates condition. The data revealed that direct physical contact between Cagemates reduced their ethanol intake, even while stimulating ethanol intake of the Drinker on the other side of the barrier, indicating that the effects of social stimulation on ethanol drinking are not entirely due to effects of modeling or peer pressure. The PCD procedures allow the evaluation of effects of a broad range of social factors on home cage ethanol drinking in mice. PMID:25447404

  9. Ethanol and neuronal metabolism.

    PubMed

    Mandel, P; Ledig, M; M'Paria, J R

    1980-01-01

    The effect of ethanol on membrane enzymes (Na+, K+ and Mg2+ ATPases, 5'-nucleotidase, adenylate cyclase) alcohol dehydrogenase, aldehyde dehydrogenase and superoxide dismutase were studied in nerve cells (established cell lines, primary cultures of chick and rat brain) cultured in the presence of 100 mM ethanol, and in total rat brain, following various ethanol treatments of the rats (20% ethanol as the sole liquid source, intraperitoneal injection). The results show a difference between neuronal and glial cells. Most of the observed changes in enzymatic activities returned rapidly to control values when ethanol was withdrawn from the culture medium or from the diet. Alcohol dehydrogenase was more stimulated by ethanol than aldehyde dehydrogenase; therefore acetaldehyde may be accumulated. The inhibition of superoxide dismutase activity may allow an accumulation of cytotoxic O2- radicals in nervous tissue and may explain the polymorphism of lesions brought about by alcohol intoxication. PMID:6264495

  10. 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.

  11. Ethanol immunosuppression in vitro

    SciTech Connect

    Kaplan, D.R.

    1986-03-01

    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 2 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.

  12. S6 Kinase Reflects and Regulates Ethanol-Induced Sedation

    PubMed Central

    Acevedo, Summer F.; Peru y Colón de Portugal, Raniero L.; Gonzalez, Dante A.; Rodan, Aylin R.

    2015-01-01

    Alcohol use disorders (AUDs) affect people at great individual and societal cost. Individuals at risk for AUDs are sensitive to alcohol's rewarding effects and/or resistant to its aversive and sedating effects. The molecular basis for these traits is poorly understood. Here, we show that p70 S6 kinase (S6k), acting downstream of the insulin receptor (InR) and the small GTPase Arf6, is a key mediator of ethanol-induced sedation in Drosophila. S6k signaling in the adult nervous system determines flies' sensitivity to sedation. Furthermore, S6k activity, measured via levels of phosphorylation (P-S6k), is a molecular marker for sedation and overall neuronal activity: P-S6k levels are decreased when neurons are silenced, as well as after acute ethanol sedation. Conversely, P-S6k levels rebound upon recovery from sedation and are increased when neuronal activity is enhanced. Reducing neural activity increases sensitivity to ethanol-induced sedation, whereas neuronal activation decreases ethanol sensitivity. These data suggest that ethanol has acute silencing effects on adult neuronal activity, which suppresses InR/Arf6/S6k signaling and results in behavioral sedation. In addition, we show that activity of InR/Arf6/S6k signaling determines flies' behavioral sensitivity to ethanol-induced sedation, highlighting this pathway in acute responses to ethanol. SIGNIFICANCE STATEMENT Genetic factors play a major role in the development of addiction. Identifying these genes and understanding their molecular mechanisms is a necessary first step in the development of targeted therapeutic intervention. Here, we show that signaling from the insulin receptor in Drosophila neurons determines flies' sensitivity to ethanol-induced sedation. We show that this signaling cascade includes the small GTPase Arf6 and S6 kinase (S6k). In addition, activity of S6k is regulated by acute ethanol exposure and by neuronal activity. S6k activity is therefore both an acute target of ethanol exposure and

  13. Cytisine modulates chronic voluntary ethanol consumption and ethanol-induced striatal up-regulation of ΔFosB in mice.

    PubMed

    Sajja, Ravi Kiran; Rahman, Shafiqur

    2013-06-01

    Chronic administration of ethanol induces persistent accumulation of ΔFosB, an important transcription factor, in the midbrain dopamine system. This process underlies the progression to addiction. Previously, we have shown that cytisine, a neuronal nicotinic acetylcholine receptor (nAChR) partial agonist, reduces various ethanol-drinking behaviors and ethanol-induced striatal dopamine function. However, the effects of cytisine on chronic ethanol drinking and ethanol-induced up-regulation of striatal ΔFosB are not known. Therefore, we examined the effects of cytisine on chronic voluntary ethanol consumption and associated striatal ΔFosB up-regulation in C57BL/6J mice using behavioral and biochemical methods. Following the chronic voluntary consumption of 15% (v/v) ethanol under a 24-h two-bottle choice intermittent access (IA; 3 sessions/week) or continuous access (CA; 24 h/d and 7 d/week) paradigm, mice received repeated intraperitoneal injections of saline or cytisine (0.5 or 3.0 mg/kg). Ethanol and water intake were monitored for 24 h post-treatment. Pretreatment with cytisine (0.5 or 1.5 mg/kg) significantly reduced ethanol consumption and preference in both paradigms at 2 h and 24 h post-treatment. The ΔFosB levels in the ventral and dorsal striatum were determined by Western blotting 18-24 h after the last point of ethanol access. In addition, cytisine (0.5 mg/kg) significantly attenuated up-regulation of ΔFosB in the ventral and dorsal striatum following chronic ethanol consumption in IA and CA paradigms. The results indicate that cytisine modulates chronic voluntary ethanol consumption and reduces ethanol-induced up-regulation of striatal ΔFosB. Further, the data suggest a critical role of nAChRs in chronic ethanol-induced neurochemical adaptations associated with ethanol addiction. PMID:23601929

  14. Dietary Reference Intakes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Dietary Reference Intakes (DRI) are recommendations intended to provide a framework for nutrient intake evaluation, as well as meal planning on the basis of nutrient adequacy. They are nutrient, not food based recommendations, created with chronic disease risk reduction as the primary goal, as ...

  15. Deletion of vanilloid receptor (TRPV1) in mice alters behavioral effects of ethanol

    PubMed Central

    Blednov, Y.A.; Harris, R.A.

    2009-01-01

    The vanilloid receptor TRPV1 is activated by ethanol and this may be important for some of the central and peripheral actions of ethanol. To determine if this receptor has a role in ethanol-mediated behaviors, we studied null mutant mice in which the Trpv1 gene was deleted. Mice lacking this gene showed significantly higher preference for ethanol and consumed more ethanol in a two-bottle choice test as compared with wild type littermates. Null mutant mice showed shorter duration of loss of righting reflex induced by low doses of ethanol (3.2 and 3.4 g/kg) and faster recovery from motor incoordination induced by ethanol (2 g/kg). However, there were no differences between null mutant and wild type mice in severity of ethanol-induced acute withdrawal (4 g/kg) or conditioned taste aversion to ethanol (2.5 g/kg). Two behavioral phenotypes (decreased sensitivity to ethanol-induced sedation and faster recovery from ethanol-induced motor incoordination) seen in null mutant mice were reproduced in wild type mice by injection of a TRPV1 antagonist, capsazepine (10 mg/kg). These two ethanol behaviors were changed in the opposite direction after injection of capsaicin, a selective TRPV1 agonist, in wild type mice. The studies provide the first evidence that TRPV1 is important for specific behavioral actions of ethanol. PMID:19705551

  16. Fetal Learning About Ethanol and Later Ethanol Responsiveness: Evidence Against “Safe” Amounts of Prenatal Exposure

    PubMed Central

    Abate, Paula; Pueta, Mariana; Spear, Norman E.; Molina, Juan C.

    2009-01-01

    Near-term fetuses of different mammalian species, including humans, exhibit functional sensory and learning capabilities. The neurobiological literature indicates that the unborn organism processes sensory stimuli present in the amniotic fluid, retains this information for considerable amounts of time, and is also capable of associating such stimuli with biologically relevant events. This research has stimulated studies aimed at the analysis of fetal and neonatal learning about ethanol, a topic that constitutes the core of the present review. Ethanol has characteristic sensory (olfactory, taste, and trigeminal) attributes and can exert pharmacologic reinforcing effects. The studies under examination support the hypothesis that low to moderate levels of maternal ethanol intoxication during late pregnancy set the opportunity for fetal learning about ethanol. These levels of prenatal ethanol exposure do not generate evident morphologic or neurobehavioral alterations in the offspring, but they exert a significant impact upon later ethanol-seeking and intake behaviors. Supported by preclinical and clinical findings, this review contributes to strengthening the case for the ability of prenatal ethanol exposure to have effects on the postnatal organism. PMID:18222969

  17. Tolerance and withdrawal in goldfish exposed to ethanol.

    PubMed

    Crawshaw, Larry I; Wallace, Helen L; O'Connor, Candace S; Yoda, Tamae; Crabbe, John C

    2006-03-30

    Acute ethanol exposure decreases regulated body temperature. Tolerance and dependence develop with continued exposure. Removal of ethanol following chronic exposure produces withdrawal. There is little information on the time course for the development of tolerance and disagreement about the presence of a rebound effect on body temperature during withdrawal. For tolerance, we monitored the selected temperature [T(sel)] of goldfish [Carassius auratus] for 8 h while they were exposed to one of three doses of ethanol. During the period from 90 to 150 min post-exposure, T(sel) was: control: 24.1+/-0.07 degrees C; 0.4% ethanol: 21.9+/-0.09 degrees C; 0.8% ethanol: 21.3+/-0.05 degrees C; 1.1% ethanol: 18.4+/-0.10 degrees C. The difference between control and experimental T(sel) decreased by the following amounts for the final 1.5 h in the gradient: 0.4% ethanol: 2.60+/-0.12 degrees C; 0.8% ethanol: 1.58+/-0.09 degrees C; 1.1% ethanol: 4.08+/-0.12 degrees C. At all 3 doses, tolerance proceeded in a stepwise manner rather than continuously. Temperature regulation during withdrawal was evaluated by maintaining the goldfish in 0.8% ethanol for three days and subsequently monitoring T(sel) in an ethanol-free temperature gradient for 36 h. During withdrawal there was no evidence for an effect on T(sel); experimental and control values were nearly identical. PMID:16448677

  18. Dehydrate ethanol without distillation

    SciTech Connect

    Not Available

    1993-10-01

    Usina da Pedra (Serrana, state of Sao Paulo, Brazil) produces 60 million gal/yr of ethanol in 180 operating days. Until this year, the plant made 96 vol.% ethanol that is used as automotive fuel, and absolute ethanol (99.5 vol. %), which is blended with gasoline. Water is the remainder in both products. The ethanol is produced from the fermentation of sugar cane, and distilled with benzene. Benzene lowers the boiling point of the ethanol-water mixture and ties up the water. In May, Usina da Pedra installed a process that dehydrates ethanol by adsorption, not distillation. A vapor-phase process containing molecular sieves, handles throughputs as high as 160,000 acfh and has a maximum capacity of 70 million gal/yr. In addition to generating safer products, the energy savings gained by switching from distillation to adsorption are significant. The adsorptive system requires input of only 2,900 Btu per gallon of ethanol; one-third the energy consumed by distillation systems that employ benzene or cyclohexane.

  19. Prenatal ethanol exposure affects temperature responses of adult rats to pentobarbital and diazepam alone and in combination with ethanol.

    PubMed

    Taylor, A N; Branch, B J; Randolph, D; Hill, M A; Kokka, N

    1987-06-01

    Long-term effects of prenatal alcohol exposure on body temperature responses to pentobarbital and diazepam and to either drug in combination with ethanol were studied in adult rats who were the offspring of dams fed a 5.0% w/v ethanol-containing liquid diet during the last 2 weeks of gestation. Adult offspring of pair-fed and chow-fed dams served as nutritional and normal controls, respectively. Pentobarbital (6.25-25.0 mg/kg) and diazepam (2.5-10.0 mg/kg) produced significantly greater dose-related hypothermic responses in females than males. Following either pentobarbital or diazepam administration female prenatally ethanol-exposed (E) rats responded with a greater fall in body temperature than the controls. Significantly greater hypothermia occurred in both male and female E rats than in controls when ethanol (1.5 g/kg) was administered together with pentobarbital or diazepam. However, the drug combinations did not produce additive effects on body temperature in any prenatal treatment group. Pentobarbital produced acute cross-tolerance to ethanol while diazepam potentiated ethanol's effect. These studies confirm and extend our previous findings of enhanced hypothermic responses to ethanol in adult rats exposed to ethanol in utero and indicate that maternal alcohol consumption produces long-term effects on the central thermoregulatory systems of offspring. PMID:3307489

  20. Proposed standards for acute exposure to low enrichment uranium for compliance with 10 CFR 70.61.

    PubMed

    Kathren, Ronald L; Burklin, Richard K

    2008-08-01

    Title 10, Code of Federal Regulations Part 70, puts forth requirements for licensure of special nuclear material including specific risk criteria for acute intakes based on biological effects. Standards for acute oral and inhalation intakes of soluble low enrichment are proposed for the three levels of biological effects given in the regulations. These levels were developed largely from available human data and have a large measure of conservatism. The proposed threshold for life endangerment was 500 mg for acute inhalation intakes and 2,500 mg for acute ingestion intakes. Acute intakes of 1,400 mg for ingestion and 100 mg for inhalation are proposed as thresholds for irreversible or serious long lasting health effects. For minor transient health effects, the proposed levels are 410 and 30 mg, respectively, for acute ingestion and inhalation intakes. For acute intakes below these levels, no demonstrable toxicological effects are anticipated. PMID:18617794

  1. Ethanol-Induced Neurodegeneration and Glial Activation in the Developing Brain.

    PubMed

    Saito, Mariko; Chakraborty, Goutam; Hui, Maria; Masiello, Kurt; Saito, Mitsuo

    2016-01-01

    Ethanol induces neurodegeneration in the developing brain, which may partially explain the long-lasting adverse effects of prenatal ethanol exposure in fetal alcohol spectrum disorders (FASD). While animal models of FASD show that ethanol-induced neurodegeneration is associated with glial activation, the relationship between glial activation and neurodegeneration has not been clarified. This review focuses on the roles of activated microglia and astrocytes in neurodegeneration triggered by ethanol in rodents during the early postnatal period (equivalent to the third trimester of human pregnancy). Previous literature indicates that acute binge-like ethanol exposure in postnatal day 7 (P7) mice induces apoptotic neurodegeneration, transient activation of microglia resulting in phagocytosis of degenerating neurons, and a prolonged increase in glial fibrillary acidic protein-positive astrocytes. In our present study, systemic administration of a moderate dose of lipopolysaccharides, which causes glial activation, attenuates ethanol-induced neurodegeneration. These studies suggest that activation of microglia and astrocytes by acute ethanol in the neonatal brain may provide neuroprotection. However, repeated or chronic ethanol can induce significant proinflammatory glial reaction and neurotoxicity. Further studies are necessary to elucidate whether acute or sustained glial activation caused by ethanol exposure in the developing brain can affect long-lasting cellular and behavioral abnormalities observed in the adult brain. PMID:27537918

  2. BK channel β1 and β4 auxiliary subunits exert opposite influences on escalated ethanol drinking in dependent mice.

    PubMed

    Kreifeldt, Max; Le, David; Treistman, Steven N; Koob, George F; Contet, Candice

    2013-01-01

    Large conductance calcium-activated potassium (BK) channels play a key role in the control of neuronal activity. Ethanol is a potent activator of BK channel gating, but how this action may impact ethanol drinking still remains poorly understood. Auxiliary β subunits are known to modulate ethanol-induced potentiation of BK currents. In the present study, we investigated whether BK β1 and β4 subunits influence voluntary ethanol consumption using knockout (KO) mice. In a first experiment, mice were first subjected to continuous two-bottle choice (2BC) and were then switched to intermittent 2BC, which progressively increased ethanol intake as previously described in wildtype mice. BK β1 or β4 subunit deficiency did not affect ethanol self-administration under either schedule of access. In a second experiment, mice were first trained to drink ethanol in a limited-access 2BC paradigm. BK β1 or β4 deletion did not affect baseline consumption. Weeks of 2BC were then alternated with weeks of chronic intermittent ethanol (CIE) or air inhalation. As expected, a gradual escalation of ethanol drinking was observed in dependent wildtype mice, while intake remained stable in non-dependent wildtype mice. However, CIE exposure only produced a mild augmentation of ethanol consumption in BK β4 KO mice. Conversely, ethanol drinking increased after fewer CIE cycles in BK β1 KO mice than in wildtype mice. In conclusion, BK β1 or β4 did not influence voluntary ethanol drinking in non-dependent mice, regardless of the pattern of access to ethanol. However, deletion of BK β4 attenuated, while deletion of BK β1 accelerated, the escalation of ethanol drinking during withdrawal from CIE. Our data suggest that BK β1 and β4 subunits have an opposite influence on the negative reinforcing properties of ethanol withdrawal. Modulating the expression, distribution or interactions of BK channel auxiliary subunits may therefore represent a novel avenue for the treatment of alcoholism

  3. Effects of anti-phospholipase A(2) antibody supplementation on dry matter intake feed efficiency, acute phase response, and blood differentials of steers fed forage- and grain-based diets.

    PubMed

    Mercadante, V R G; Waters, K M; Marquezini, G H L; Henry, D D; Ciriaco, F M; Arthington, J D; DiLorenzo, N; Lamb, G C

    2015-02-01

    To determine whether supplementation of anti-phospholipase A antibody (aPLA) would alter voluntary DMI, feed efficiency (FE), acute-phase protein concentration, and blood differentials (BD) due to a change in diet from a forage-based to a grain-based diet, individual daily DMI was measured on 80 cross-bred steers during a 141-d period. On d 0, steers were blocked by BW and randomly assigned to receive a growing forage diet containing 1) no additive (CON; = 20), 2) inclusion of 30 mg of monensin and 8.8 mg of tylosin per kg of diet DM (MT; = 20), 3) inclusion of an aPLA supplement at 0.4% of the diet DM (0.4% aPLA; = 20), and 4) inclusion of an aPLA supplement at 0.2% of the diet DM (0.2% aPLA; = 20). On d 60, steers were transitioned into a grain-based diet (90% concentrate) over a 21-d "step-up" period while continuing to receive their supplement treatments and were maintained on the high-grain diet until the end of the trial on d 141. On d 0, 60, 81, and 141, individual shrunk BW was recorded. Blood samples were collected on d 60, 63, 65, 67, 70, 72, 74, 77, 79, 81, and 84 for determination of concentration of plasma ceruloplasmin, haptoglobin, and BD. During the growing forage-diet period, steers from the 0.2% aPLA and 0.4% aPLA treatments had lower ( < 0.05) residual feed intake (RFI; -0.12 ± 0.13 and -0.22 ± 0.13 kg/d, respectively) than steers from the CON treatment (0.31 ± 0.13 kg/d). During the grain-based diet period, the 0.2% aPLA (-0.12 ± 0.10 kg/d), 0.4% aPLA (0.36 ± 0.10 kg/d), and MT (0.10 ± 0.10 kg/d) steers had greater ( = 0.04) RFI than CON steers (-0.37 ± 0.10 kg/d). During the transition phase, white blood cell counts were greater ( = 0.04) for the 0.2% aPLA treatment (13.61 × 10 ± 0.42 × 10 cells/μL) than the 0.4% aPLA and MT treatments (12.16 × 10 ± 0.42 × 10 and 12.37 × 10 ± 0.42 × 10 cells/μL, respectively) and concentrations of lymphocytes also were greater ( = 0.01) for the 0.2% aPLA treatment (7.66 × 10 ± 0.28 × 10

  4. UNC-18 modulates ethanol sensitivity in Caenorhabditis elegans.

    PubMed

    Graham, Margaret E; Edwards, Mark R; Holden-Dye, Lindy; Morgan, Alan; Burgoyne, Robert D; Barclay, Jeff W

    2009-01-01

    Acute ethanol exposure affects the nervous system as a stimulant at low concentrations and as a depressant at higher concentrations, eventually resulting in motor dysfunction and uncoordination. A recent genetic study of two mouse strains with varying ethanol preference indicated a correlation with a polymorphism (D216N) in the synaptic protein Munc18-1. Munc18-1 functions in exocytosis via a number of discrete interactions with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein syntaxin-1. We report that the mutation affects binding to syntaxin but not through either a closed conformation mode of interaction or through binding to the syntaxin N terminus. The D216N mutant instead has a specific impairment in binding the assembled SNARE complex. Furthermore, the mutation broadens the duration of single exocytotic events. Expression of the orthologous mutation (D214N) in the Caenorhabditis elegans UNC-18 null background generated transgenic rescues with phenotypically similar locomotion to worms rescued with the wild-type protein. Strikingly, D214N worms were strongly resistant to both stimulatory and sedative effects of acute ethanol. Analysis of an alternative Munc18-1 mutation (I133V) supported the link between reduced SNARE complex binding and ethanol resistance. We conclude that ethanol acts, at least partially, at the level of vesicle fusion and that its acute effects are ameliorated by point mutations in UNC-18. PMID:18923141

  5. Inhibitory effects of ethanol on phosphatidylinositol breakdown in pancreatic acini

    SciTech Connect

    Towner, S.J.; Peppin, J.F.; Tsukamoto, H.

    1986-03-01

    Recently the physiological relationship between the phospholipid effect and secretagogue-induced cellular function has begun to be understood. In this study, the authors investigated acute and chronic effects of ethanol on phosphatidylinositol (PI) synthesis and breakdown in pancreatic acini. Five pairs of male Wistar rats were intragastrically infused for 30 days with high fat diet (25% total calories) plus ethanol or isocaloric dextrose. After intoxication, isolated in HEPES media, followed by 30 min incubation with CCK-8 (0, 100, 300 or 600 pM) and ethanol (0 or 100 mM). Acinar lipids were extracted and counted for labeled PI. Incorporation of /sup 3/H-inositol into alcoholic acinar PI was reduced to 38.2% of that in controls. A percent maximal PI break down by CCK-8 was similar in the two groups (13-24% of basal). However, the magnitude of PI breakdown was markedly lower in alcoholic acini (482 vs 1081 dpm) due to the decreased PI synthesis rate. The presence of 100 mM ethanol in the media further inhibited the breakdown by 50% in this group. These results strongly indicate that chronic ethanol intoxication inhibits PI synthesis and breakdown in pancreatic acini, and that this inhibition can be potentiated by acute ethanol administration.

  6. Ethanol and oxidative stress.

    PubMed

    Sun, A Y; Ingelman-Sundberg, M; Neve, E; Matsumoto, H; Nishitani, Y; Minowa, Y; Fukui, Y; Bailey, S M; Patel, V B; Cunningham, C C; Zima, T; Fialova, L; Mikulikova, L; Popov, P; Malbohan, I; Janebova, M; Nespor, K; Sun, G Y

    2001-05-01

    This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Albert Y. Sun. The presentations were (1) Ethanol-inducible cytochrome P-4502E1 in alcoholic liver disease, by Magnus Ingelman-Sundberg and Etienne Neve; (2) Regulation of NF-kappaB by ethanol, by H. Matsumoto, Y. Nishitani, Y. Minowa, and Y. Fukui; (3) Chronic ethanol consumption increases concentration of oxidized proteins in rat liver, by Shannon M. Bailey, Vinood B. Patel, and Carol C. Cunningham; (4) Antiphospholipids antibodies and oxidized modified low-density lipoprotein in chronic alcoholic patients, by Tomas Zima, Lenka Fialova, Ludmila Mikulikova, Ptr Popov, Ivan Malbohan, Marta Janebova, and Karel Nespor; and (5) Amelioration of ethanol-induced damage by polyphenols, by Albert Y. Sun and Grace Y. Sun. PMID:11391077

  7. Process for producing ethanol

    SciTech Connect

    Lantero, O.J.; Fish, J.J.

    1993-07-27

    A process is described for producing ethanol from raw materials containing a high dry solid mash level having fermentable sugars or constituents which can be converted into sugars, comprising the steps of: (a) liquefaction of the raw materials in the presence of an alpha amylase to obtain liquefied mash; (b) saccharification of the liquefied mash in the presence of a glucoamylase to obtain hydrolysed starch and sugars; (c) fermentation of the hydrolysed starch and sugars by yeast to obtain ethanol; and (d) recovering the obtained ethanol, wherein an acid fungal protease is introduced to the liquefied mash during the saccharification and/or to the hydrolysed starch and sugars during the fermentation, thereby increasing the rate of production of ethanol as compared to a substantially similar process conducted without the introduction of the protease.

  8. Biofuel Ethanol Transport Risk

    EPA Science Inventory

    Ethanol production has increased rapidly over the last 10 years and many communities lack awareness of the increased and growing extent of biofuel transportation through their jurisdictions. These communities and their emergency responders may not have the information and resour...

  9. Ethanol production from lignocellulose

    DOEpatents

    Ingram, Lonnie O.; Wood, Brent E.

    2001-01-01

    This invention presents a method of improving enzymatic degradation of lignocellulose, as in the production of ethanol from lignocellulosic material, through the use of ultrasonic treatment. The invention shows that ultrasonic treatment reduces cellulase requirements by 1/3 to 1/2. With the cost of enzymes being a major problem in the cost-effective production of ethanol from lignocellulosic material, this invention presents a significant improvement over presently available methods.

  10. Up-regulation of gamma-aminobutyric acid transporter I mediates ethanol sensitivity in mice.

    PubMed

    Hu, J-H; Ma, Y-H; Yang, N; Mei, Z-T; Zhang, M-H; Fei, J; Guo, L-H

    2004-01-01

    Ethanol is among the most widely abused drugs in the world. Chronic ethanol consumption leads to ethanol tolerance and addiction, and impairs learning and memory. Na+/Cl- dependent GABA transporters play an important role in controlling the concentration of GABA in the synaptic cleft, and thus they control the intensity and duration of synaptic transmission of GABA. It has been suggested that GABAergic system is involved in ethanol consumption, tolerance and addiction, because chronic ethanol consumption alters the expression of GABAA receptors and drugs on GABA receptors affect ethanol actions. The results of the present study reveal that that activity of GABA transporters in mouse brain after 15-min acute ethanol injection or after chronic ethanol consumption is increased. Moreover, mice pre-injected with a competitive or a noncompetitive antagonist of gamma-aminobutyric acid transporter subtype 1 (GAT1) showed high sensitivity to the sedative/hypnotic effects of ethanol. In contrast, transgenic mice overexpressing GAT1 displayed low sensitivity to ethanol, as shown by the righting reflex test. Mice overexpressing GAT1 survived a lethal dose of ethanol (9 g/kg, i.p.) longer, maintained locomotor activity longer after a sub-lethal dose (1.75 g/kg, i.p.) and exhibited a higher median lethal dose than wild-type littermates. These results suggest that GAT1 plays an important role in sensitivity to ethanol, and might be a therapeutic target for alcoholism prevention and treatment. Acute and chronic ethanol administration resulted in the increase of GABA transporter function. Use of GAT1 selective inhibitors and GAT1 overexpressing mice thus demonstrate that GAT1 should be an important protein mediating sensitivity to ethanol in mice. PMID:14751274

  11. Ablation of μ opioid receptor-expressing GABA neurons in rostromedial tegmental nucleus increases ethanol consumption and regulates ethanol-related behaviors.

    PubMed

    Fu, Rao; Chen, Xing; Zuo, Wanhong; Li, Jing; Kang, Seungwoo; Zhou, Li-Hua; Siegel, Allan; Bekker, Alex; Ye, Jiang-Hong

    2016-08-01

    There has been increasing interest in the rostromedial tegmental nucleus (RMTg), given its potential regulatory role in many aversion-related behaviors. The RMTg contains mostly GABAergic neurons, sends a dense inhibitory projection to dopamine neurons in the midbrain, and is rich with μ-opioid receptors (MOR). Like most addictive drugs, ethanol has both aversive and rewarding properties. However, the cellular mechanisms underlying the effects of ethanol, particularly the aversive effect that limits its intake are not well understood. Recent studies have linked aversion with synaptic inhibition of dopamine neurons in the ventral tegmental area. To determine a potential role that the RMTg plays in the effect of ethanol, in this study, we employed a neurotoxin, dermorphin-saporin (DS), to lesion RMTg neurons prior to assessing ethanol-related behaviors. Rats were infused with DS bilaterally into the RMTg. This manipulation substantially increased the intake and preference for ethanol but not sucrose. It also reduced the number of neurons with MOR and glutamic acid decarboxylase 67 immunoreactivity within the RMTg. These changes did not occur after intra-RMTg infusion of blank saporin or vehicle. Importantly, intra-RMTg DS infusion significantly enhanced expression of conditioned place preference induced by ethanol (2 g/kg, i.p.), and slowed the extinction process. These results suggest that MOR-expressing GABAergic neurons in the RMTg contribute significantly to the regulation of ethanol consumption and related behaviors. PMID:26921770

  12. Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption

    SciTech Connect

    Thanos, P.K.; Wang, G.; Thanos, P.K.; Gopez, V.; Delis, F.; Michaelides, M.; Grand, D.K.; Wang, G.-J.; Kunos, G.; Volkow, N.D.

    2011-01-01

    The anatomical proximity of the cannabinoid type 1 (CNR1/CB1R) and the dopamine D2 receptors (DRD2), their ability to form CB1R-DRD2 heteromers, their opposing roles in locomotion, and their involvement in ethanol's reinforcing and addictive properties prompted us to study the levels and distribution of CB1R after chronic ethanol intake, in the presence and absence of DRD2. We monitored the drinking patterns and locomotor activity of Drd2+/+ and Drd2-/- mice consuming either water or a 20% (v/v) ethanol solution (forced ethanol intake) for 6 months and used the selective CB1 receptor antagonist [{sup 3}H]SR141716A to quantify CB1R levels in different brain regions with in vitro receptor autoradiography. We found that the lack of DRD2 leads to a marked upregulation (approximately 2-fold increase) of CB1R in the cerebral cortex, the caudate-putamen, and the nucleus accumbens, which was reversed by chronic ethanol intake. The results suggest that DRD2-mediated dopaminergic neurotransmission and chronic ethanol intake exert an inhibitory effect on cannabinoid receptor expression in cortical and striatal regions implicated in the reinforcing and addictive properties of ethanol.

  13. Ethanol metabolism in the gastrointestinal tract and its possible consequences.

    PubMed

    Seitz, H K; Gärtner, U; Egerer, G; Simanowski, U A

    1994-01-01

    Ethanol is oxidised not only in the liver, but also in the gastrointestinal tract. Although this ethanol metabolism is less than that of the liver, it has some important relevance with respect to the first pass metabolism of alcohol and to ethanol induced tissue toxicity. In the gastrointestinal tract, ethanol can be metabolised not only in the mucosal cell via alcohol dehydrogenase (ADH) and microsomal ethanol oxidising system (MEOS), but also in a great variety of bacteria. Depending on the gastrointestinal location, one or the other metabolic pathway of alcohol may be predominant. The metabolism of ethanol by gastric ADH, the so called first pass metabolism, influences ethanol blood concentrations not only in the portal vein and thus in the liver, but also in the systemic circulation. As gastric ADH activity is decreased in younger women, in the elderly, in the alcoholic, during fasting and after treatment with certain H-2-receptor antagonists, increased blood ethanol concentrations may occur in these situations after oral intake of ethanol. However, this first pass metabolism of alcohol is influenced not only by ADH activity but also by the speed of gastric emptying (e.g. slow gastric emptying leads to increased first pass metabolism). Finally, gastric morphology also determines first pass metabolism. Chronic atrophic gastritis and Helicobacter pylori associated gastric injury lead to a decrease of gastric ADH activity, and thus possibly to a decreased first pass metabolism of alcohol. In addition, the local production of acetaldehyde from ethanol in the oesophagus, where significantly more sigma-ADH is present, may contribute to tissue injury and this may lead to the well known ethanol associated oesophageal cancer development. Various isoenzymes of ADH exist in the colorectum and they are also capable of producing acetaldehyde in amounts sufficient to injure the mucosa. Besides ADH, the MEOS, a mixed function oxidase, also metabolises ethanol. This system is

  14. Increased consumption of ethanol and sugar water in mice lacking the dopamine D2 long receptor.

    PubMed

    Bulwa, Zachary B; Sharlin, Jordan A; Clark, Peter J; Bhattacharya, Tushar K; Kilby, Chessa N; Wang, Yanyan; Rhodes, Justin S

    2011-11-01

    Individual differences in dopamine D2 receptor (D2R) expression in the brain are thought to influence motivation and reinforcement for ethanol and other rewards. D2R exists in two isoforms, D2 long (D2LR) and D2 short (D2SR), produced by alternative splicing of the same gene. The relative contributions of D2LR versus D2SR to ethanol and sugar water drinking are not known. Genetic engineering was used to produce a line of knockout (KO) mice that lack D2LR and consequently have increased expression of D2SR. KO and wild-type (WT) mice of both sexes were tested for intake of 20% ethanol, 10% sugar water and plain tap water using established drinking-in-the-dark procedures. Mice were also tested for effects of the D2 antagonist eticlopride on intake of ethanol to determine whether KO responses were caused by lack of D2LR or overrepresentation of D2SR. Locomotor activity on running wheels and in cages without wheels was also measured for comparison. D2L KO mice drank significantly more ethanol than WT in both sexes. KO mice drank more sugar water than WT in females but not in males. Eticlopride dose dependently decreased ethanol intake in all groups except male KO. KO mice were less physically active than WT in cages with or without running wheels. Results suggest that overrepresentation of D2SR contributes to increased intake of ethanol in the KO mice. Decreasing wheel running and general levels of physical activity in the KO mice rules out the possibility that higher intake results from higher motor activity. Results extend the literature implicating altered expression of D2R in risk for addiction by delineating the contribution of individual D2R isoforms. These findings suggest that D2LR and D2SR play differential roles in consumption of alcohol and sugar rewards. PMID:21803530

  15. Central histaminergic transmission modulates the ethanol induced anxiolysis in mice.

    PubMed

    Verma, Lokesh; Jain, Nishant S

    2016-10-15

    Intrigued by the report demonstrating an increase in brain histamine levels by ethanol administration and central histamine transmission to affect the anxiety related behaviors, the present study examined the permissive role of central histaminergic transmission in the acute anxiolytic-like effect of the ethanol on elevated plus maze (EPM) in mice. Results demonstrated that prior administration of the agents that are known to enhance the brain histamine transmission, i.e. low dose of histamine (0.1μg/mouse, i.c.v.) or histamine precursor, l-histidine (500, 1000mg/kg, i.p.) or low dose of histamine releasing agent (H3 receptor inverse agonist), thioperamide (2μg/mouse) attenuated the acute anitanxiety-like effect of ethanol (2g/kg, i.p, 8% w/v) in mice on EPM. However, pre-treatment with the H1 receptor antagonist, cetirizine (0.1μg/mouse, i.c.v.) or H2 receptor antagonist, ranitidine (50μg/mouse, i.c.v.) failed to affect the attenuating effect of low dose of histamine on ethanol induced anxiolysis. On the other hand, only H1 receptor antagonist, cetirizine (0.1μg/mouse, i.c.v.) was able to partially reverse the attenuation of ethanol induced anxiolysis by l-histidine (1000mg/kg, i.p.). Surprisingly, in mice pre-treated with the higher dose of histamine (50μg/mouse, i.c.v.) or thioperamide (10μg/mouse, i.c.v.), the ethanol (2g/kg, i.p.) induced antianxiety-like effect was further enhanced on EPM. Furthermore, this potentiating effect of high dose of histamine on the ethanol (2g/kg, i.p.) was exacerbated on pre-treatment with the H1 receptor antagonist, cetirizine, while H2 receptor antagonist, ranitidine completely reversed this action of high dose of histamine on ethanol. Supportive to these results, i.c.v. pre-treatment with H1 receptor agonist, FMPH (2, 6.5μg/mouse, i.c.v.) attenuated while H2 receptor agonist, amthamine (0.1, 0.5μg/mouse, i.c.v.) enhanced the ethanol induced anxiolysis in mice. Thus, it is reasonable to contemplate that central

  16. Inhibitors of biofilm formation by fuel ethanol contaminants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Industrial fuel ethanol production suffers from chronic and acute infections that reduce yields and cause “stuck fermentations” that result in costly shutdowns. Lactic acid bacteria, particularly Lactobacillus sp., are recognized as major contaminants. In previous studies, we observed that certain...

  17. Chronic Intermittent Ethanol Exposure Alters Stress Effects on (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP) Immunolabeling of Amygdala Neurons in C57BL/6J Mice.

    PubMed

    Maldonado-Devincci, Antoniette M; Kampov-Polevoi, Alexander; McKinley, Raechel E; Morrow, Danielle H; O'Buckley, Todd K; Morrow, A Leslie

    2016-01-01

    The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP, allopregnanolone) is decreased in various brain regions of C57BL/6J mice following exposure to an acute stressor or chronic intermittent ethanol (CIE) exposure and withdrawal. It is well established that there are complex interactions between stress and ethanol drinking, with mixed literature regarding the effects of stress on ethanol intake. However, there is little research examining how chronic ethanol exposure alters stress responses. The present work examined the impact of CIE exposure and withdrawal on changes in brain levels of 3α,5α-THP, as well as hormonal and behavioral responses to forced swim stress (FSS). Adult male C57BL/6J mice were exposed to four cycles of CIE to induce ethanol dependence. Following 8 h or 72 h withdrawal, mice were subjected to FSS for 10 min, and 50 min later brains were collected for immunohistochemical analysis of cellular 3α,5α-THP. Behavioral and circulating corticosterone responses to FSS were quantified. Following 8 h withdrawal, ethanol exposure potentiated the corticosterone response to FSS. Following 72 h withdrawal, this difference was no longer observed. Following 8 h withdrawal, stress-exposed mice showed no differences in immobility, swimming or struggling behavior. However, following 72 h withdrawal, ethanol-exposed mice showed less immobility and greater swimming behavior compared to air-exposed mice. Interestingly, cellular 3α,5α-THP levels were increased in the lateral amygdala 8 h and 72 h post-withdrawal in stressed ethanol-exposed mice compared to ethanol-exposed/non-stressed mice. In the paraventricular nucleus of the hypothalamus, stress exposure decreased 3α,5α-THP levels compared to controls following 72 h withdrawal, but no differences were observed 8 h post-withdrawal. There were no differences in cellular 3α,5α-THP levels in the nucleus accumbens shell at either withdrawal time point. These data suggest that

  18. Chronic Intermittent Ethanol Exposure Alters Stress Effects on (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP) Immunolabeling of Amygdala Neurons in C57BL/6J Mice

    PubMed Central

    Maldonado-Devincci, Antoniette M.; Kampov-Polevoi, Alexander; McKinley, Raechel E.; Morrow, Danielle H.; O’Buckley, Todd K.; Morrow, A. Leslie

    2016-01-01

    The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP, allopregnanolone) is decreased in various brain regions of C57BL/6J mice following exposure to an acute stressor or chronic intermittent ethanol (CIE) exposure and withdrawal. It is well established that there are complex interactions between stress and ethanol drinking, with mixed literature regarding the effects of stress on ethanol intake. However, there is little research examining how chronic ethanol exposure alters stress responses. The present work examined the impact of CIE exposure and withdrawal on changes in brain levels of 3α,5α-THP, as well as hormonal and behavioral responses to forced swim stress (FSS). Adult male C57BL/6J mice were exposed to four cycles of CIE to induce ethanol dependence. Following 8 h or 72 h withdrawal, mice were subjected to FSS for 10 min, and 50 min later brains were collected for immunohistochemical analysis of cellular 3α,5α-THP. Behavioral and circulating corticosterone responses to FSS were quantified. Following 8 h withdrawal, ethanol exposure potentiated the corticosterone response to FSS. Following 72 h withdrawal, this difference was no longer observed. Following 8 h withdrawal, stress-exposed mice showed no differences in immobility, swimming or struggling behavior. However, following 72 h withdrawal, ethanol-exposed mice showed less immobility and greater swimming behavior compared to air-exposed mice. Interestingly, cellular 3α,5α-THP levels were increased in the lateral amygdala 8 h and 72 h post-withdrawal in stressed ethanol-exposed mice compared to ethanol-exposed/non-stressed mice. In the paraventricular nucleus of the hypothalamus, stress exposure decreased 3α,5α-THP levels compared to controls following 72 h withdrawal, but no differences were observed 8 h post-withdrawal. There were no differences in cellular 3α,5α-THP levels in the nucleus accumbens shell at either withdrawal time point. These data suggest that

  19. Ethanol Induces Endoplasmic Reticulum Stress in the Developing Brain

    PubMed Central

    Ke, Zunji; Wang, Xin; Liu, Ying; Fan, Zhiqin; Chen, Gang; Xu, Mei; Bower, Kimberley A.; Frank, Jacqueline A.; Li, Mingtao; Fang, Shengyun; Shi, Xianglin; Luo, Jia

    2016-01-01

    Background Ethanol exposure during brain development causes profound damages to the central nervous system (CNS). The underlying cellular/molecular mechanisms remain unclear. The endoplasmic reticulum (ER) is involved in posttranslational protein processing and transport. The accumulation of unfolded or misfolded proteins in the ER lumen triggers ER stress, which is characterized by translational attenuation, synthesis of ER chaperone proteins, and activation of transcription factors. Sustained ER stress ultimately leads to cell death. ER stress is implicated in various neurodegenerative processes. Methods Using a third trimester equivalent mouse model of ethanol exposure, we tested the hypothesis that ethanol induces ER stress in the developing brain. Seven-day-old C57BL/6 mice were acutely exposed to ethanol by subcutaneous injection and the expression of ER stress-inducible proteins (ERSIPs) and signaling pathways associated with ER stress were examined. Results Ethanol exposure significantly increased the expression of ERSIPs and activated signaling pathways associated with ER stress; these include ATF6, CHOP/GADD153, GRP78, and mesencephalic astrocyte-derived neurotrophic factor as well as the phosphorylation of IRE1α, eIF2α, PERK, and PKR. The ethanol-induced increase in ERSIPs occurred within 4 hours of ethanol injection, and levels of some ERSIPs remained elevated after 24 hours of ethanol exposure. Ethanol-induced increase in phosphorylated eIF2α, caspase-12, and CHOP was distributed in neurons of specific areas of the cerebral cortex, hippocampus, and thalamus. Conclusions Our finding indicates that ethanol induces ER stress in immature neurons, providing novel insight into ethanol’s detrimental effect on the developing CNS. PMID:21599712

  20. Chronic Intermittent Ethanol Regulates Hippocampal GABA(A) Receptor Delta Subunit Gene Expression

    PubMed Central

    Follesa, Paolo; Floris, Gabriele; Asuni, Gino P.; Ibba, Antonio; Tocco, Maria G.; Zicca, Luca; Mercante, Beniamina; Deriu, Franca; Gorini, Giorgio

    2015-01-01

    Chronic ethanol consumption causes structural and functional reorganization in the hippocampus and induces alterations in the gene expression of gamma-aminobutyric acid type A receptors (GABAARs). Distinct forced intermittent exposure models have been used previously to investigate changes in GABAAR expression, with contrasting results. Here, we used repeated cycles of a Chronic Intermittent Ethanol paradigm to examine the relationship between voluntary, dependence-associated ethanol consumption, and GABAAR gene expression in mouse hippocampus. Adult male C57BL/6J mice were exposed to four 16-h ethanol vapor (or air) cycles in inhalation chambers alternated with limited-access two-bottle choice between ethanol (15%) and water consumption. The mice exposed to ethanol vapor showed significant increases in ethanol consumption compared to their air-matched controls. GABAAR alpha4 and delta subunit gene expression were measured by qRT-PCR at different stages. There were significant changes in GABAAR delta subunit transcript levels at different time points in ethanol-vapor exposed mice, while the alpha4 subunit levels remained unchanged. Correlated concurrent blood ethanol concentrations suggested that GABAAR delta subunit mRNA levels fluctuate depending on ethanol intoxication, dependence, and withdrawal state. Using a vapor-based Chronic Intermittent Ethanol procedure with combined two-bottle choice consumption, we corroborated previous evidences showing that discontinuous ethanol exposure affects GABAAR delta subunit expression but we did not observe changes in alpha4 subunit. These findings indicate that hippocampal GABAAR delta subunit expression changes transiently over the course of a Chronic Intermittent Ethanol paradigm associated with voluntary intake, in response to ethanol-mediated disturbance of GABAergic neurotransmission. PMID:26617492

  1. SENSITIZATION TO SOCIAL ANXIOLYTIC EFFECTS OF ETHANOL IN ADOLESCENT AND ADULT SPRAGUE-DAWLEY RATS FOLLOWING REPEATED ETHANOL EXPOSURE

    PubMed Central

    Varlinskaya, Elena; Spear, Linda Patia

    2009-01-01

    Ontogenetic studies using a social interaction paradigm have shown that adolescent rats are less sensitive to anxiolytic properties of acute ethanol than their adult counterparts. It is not known, however, whether adaptations to these anxiolytic effects upon repeated experiences with ethanol would be similar in adolescents and adults. The present study investigated sensitivity to the anxiolytic effects of ethanol in adolescent and adult male and female Sprague-Dawley rats following 7 days of exposure [postnatal day (P) 27–33 for adolescents and P62–68 for adults] to 1 g/kg ethanol or saline (i.p.), as well as in animals left non-manipulated during this time. Anxiolytic effects of ethanol (0, 0.75, 1.0, 1.25, and 1.5 g/kg for adolescents and 0, 0.25, 0.5, 0.75, 1.0, and 1.25 g/kg for adults in Experiments 1 and 2, respectively) were examined 48 hours after the last exposure using a modified social interaction test under unfamiliar test circumstances. At both ages, repeated ethanol exposure resulted in the development of apparent sensitization to anxiolytic effects of ethanol indexed via enhancement of social investigation and transformation of social avoidance into social indifference or preference, as well as expression of tolerance to the socially inhibiting effects induced by higher ethanol doses. Evidence for the emergence of sensitization in adults and tolerance at both ages was seen not only following chronic ethanol, but also after chronic saline exposure, suggesting that chronic manipulation per se may be sufficient to alter the sensitivity of both adolescents and adults to socially-relevant effects of ethanol. PMID:20113878

  2. MMP-2 and MMP-9 activities and TIMP-1 and TIMP-2 expression in the prostatic tissue of two ethanol-preferring rat models.

    PubMed

    Fioruci-Fontanelli, Beatriz Aparecida; Chuffa, Luiz Gustavo A; Mendes, Leonardo O; Pinheiro, Patricia Fernanda F; Delella, Flávia Karina; Kurokawa, Cilmery S; Felisbino, Sérgio Luis; Martinez, Francisco Eduardo

    2015-01-01

    We investigated whether chronic ethanol intake is capable of altering the MMP-2 and MMP-9 activities and TIMP-2 and TIMP-1 expression in the dorsal and lateral prostatic lobes of low (UChA) and high (UChB) ethanol-preferring rats. MMP-2 and MMP-9 activities and TIMP-1 and TIMP-2 expression were significantly reduced in the lateral prostatic lobe of the ethanol drinking animals. Dorsal prostatic lobe was less affected showing no significant alterations in these proteins, except for a reduction in the TIMP-1 expression in UChA rats. These important findings demonstrate that chronic ethanol intake impairs the physiological balance of the prostate extracellular matrix turnover, through downregulation of MMPs, which may contribute to the development of prostatic diseases. Furthermore, since these proteins are also components of prostate secretion, the negative impact of chronic ethanol intake on fertility may also involve reduction of MMPs and TIMPs in the seminal fluid. PMID:26258010

  3. MMP-2 and MMP-9 Activities and TIMP-1 and TIMP-2 Expression in the Prostatic Tissue of Two Ethanol-Preferring Rat Models

    PubMed Central

    Fioruci-Fontanelli, Beatriz Aparecida; Chuffa, Luiz Gustavo A.; Mendes, Leonardo O.; Pinheiro, Patricia Fernanda F.; Delella, Flávia Karina; Kurokawa, Cilmery S.; Felisbino, Sérgio Luis; Martinez, Francisco Eduardo

    2015-01-01

    We investigated whether chronic ethanol intake is capable of altering the MMP-2 and MMP-9 activities and TIMP-2 and TIMP-1 expression in the dorsal and lateral prostatic lobes of low (UChA) and high (UChB) ethanol-preferring rats. MMP-2 and MMP-9 activities and TIMP-1 and TIMP-2 expression were significantly reduced in the lateral prostatic lobe of the ethanol drinking animals. Dorsal prostatic lobe was less affected showing no significant alterations in these proteins, except for a reduction in the TIMP-1 expression in UChA rats. These important findings demonstrate that chronic ethanol intake impairs the physiological balance of the prostate extracellular matrix turnover, through downregulation of MMPs, which may contribute to the development of prostatic diseases. Furthermore, since these proteins are also components of prostate secretion, the negative impact of chronic ethanol intake on fertility may also involve reduction of MMPs and TIMPs in the seminal fluid. PMID:26258010

  4. Influence of the acute alcoholism on the phagocytic function of the mononuclear phagocytic system

    PubMed Central

    Sabino, KR; Petroianu, A; Alberti, LR

    2011-01-01

    Rationale:Alcoholics are more likely to have infections, mainly in the respiratory system. Alcohol seems to inhibit the immune system. Despite the extensive literature related to alcoholism, data related to the immune system are still not conclusive. Objective: The purpose of this study was to verify the influence of acute alcohol intake on colloid distribution in the organs of the mononuclear phagocyte system. Methods and Results: Thirteen male Swiss mice were divided into two groups: Group 1 (n = 5) – control, and Group 2 (n = 8) – animals that received 0.5 ml ethanol 50%, 30 minutes before the experiment. Colloidal sulphur labeled with ⁸⁸mTc was used to evaluate colloid distribution in the liver, spleen and lungs. Colloid clearance was assessed as well. A gamma camera was used to measure the radioactivity of these organs and of a blood clot. No difference was found in the presence of colloid in the organs of both groups. The liver showed the highest phagocytic intake, followed by the spleen and lungs (p = 0.021 for Group 1 and p = 0.003 for Group 2). A minimum amount of radiation remained in the blood of both groups. Discussion: According to the experiential conditions of this work, acute ingestion of alcohol did not interfere with the phagocytic function of the mononuclear phagocyte system in mice. PMID:22514578

  5. Behavioral economics of concurrent ethanol-sucrose and sucrose reinforcement in the rat: effects of altering variable-ratio requirements.

    PubMed Central

    Petry, N M; Heyman, G M

    1995-01-01

    These experiments examined the own-price and cross-price elasticities of a drug (ethanol mixed with 10% sucrose) and a nondrug (10% sucrose) reinforcer. Rats were presented with ethanol-sucrose and sucrose, both available on concurrent independent variable-ratio (VR) 8 schedules of reinforcement. In Experiment 1, the variable ratio for the ethanol mix was systematically raised to 10, 12, 14, 16, 20, and 30, while the variable ratio for sucrose remained at 8. Five of the 6 rats increased ethanol-reinforced responding at some of the increments and defended baseline levels of ethanol intake. However, the rats eventually ceased ethanol-reinforced responding at the highest variable ratios. Sucrose-reinforced responding was not systematically affected by the changes in variable ratio for ethanol mix. In Experiment 2, the variable ratio for sucrose was systematically increased while the ethanol-sucrose response requirement remained constant. The rats decreased sucrose-reinforced responding and increased ethanol-sucrose-reinforced responding, resulting in a two- to 10-fold increase in ethanol intake. Experiment 3 examined the substitutability of qualitatively identical reinforcers: 10% sucrose versus 10% sucrose. Increases in variable-ratio requirements at the preferred lever resulted in a switch in lever preference. Experiment 4 examined whether 10% ethanol mix substituted for 5% ethanol mix, with increasing variable-ratio requirements of the 5% ethanol. All rats eventually responded predominantly for the 10% ethanol mix, but total amount of ethanol consumed per session did not systematically change. In Experiment 5, the variable-ratio requirements for both ethanol and sucrose were simultaneously raised to VR 120; 7 of 8 rats increased ethanol-reinforced responding while decreasing sucrose-reinforced responding. These data suggest that, within this ethanol-induction procedure and within certain parameters, demand for ethanol-sucrose was relatively inelastic, and sucrose

  6. Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens

    PubMed Central

    Rose, Jamie H.; Karkhanis, Anushree N.; Chen, Rong; Gioia, Dominic; Lopez, Marcelo F.; Becker, Howard C.; McCool, Brian A.

    2016-01-01

    Background: Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. Methods: Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. Results: Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. Conclusions: These data suggest that the chronic intermittent ethanol-induced increase

  7. Daidzin suppresses ethanol consumption by Syrian golden hamsters without blocking acetaldehyde metabolism.

    PubMed Central

    Keung, W M; Lazo, O; Kunze, L; Vallee, B L

    1995-01-01

    Daidzin is a potent, selective, and reversible inhibitor of human mitochondrial aldehyde dehydrogenase (ALDH) that suppresses free-choice ethanol intake by Syrian golden hamsters. Other ALDH inhibitors, such as disulfiram (Antabuse) and calcium citrate carbimide (Temposil), have also been shown to suppress ethanol intake of laboratory animals and are thought to act by inhibiting the metabolism of acetaldehyde produced from ingested ethanol. To determine whether or not daidzin inhibits acetaldehyde metabolism in vivo, plasma acetaldehyde in daidzin-treated hamsters was measured after the administration of a test dose of ethanol. Daidzin treatment (150 mg/kg per day i.p. for 6 days) significantly suppresses (> 70%) hamster ethanol intake but does not affect overall acetaldehyde metabolism. In contrast, after administration of the same ethanol dose, plasma acetaldehyde concentration in disulfiram-treated hamsters reaches 0.9 mM, 70 times higher than that of the control. In vitro, daidzin suppresses hamster liver mitochondria-catalyzed acetaldehyde oxidation very potently with an IC50 value of 0.4 microM, which is substantially lower than the daidzin concentration (70 microM) found in the liver mitochondria of daidzin-treated hamsters. These results indicate that (i) the action of daidzin differs from that proposed for the classic, broad-acting ALDH inhibitors (e.g., disulfiram), and (ii) the daidzin-sensitive mitochondrial ALDH is not the one and only enzyme that is essential for acetaldehyde metabolism in golden hamsters. PMID:7568058

  8. alpha1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol.

    PubMed

    Walker, Brendan M; Rasmussen, Dennis D; Raskind, Murray A; Koob, George F

    2008-03-01

    The purpose of this study was to test the hypothesis that blockade of alpha1-adrenergic receptors may suppress the excessive ethanol consumption associated with acute withdrawal in ethanol-dependent rats. Following the acquisition and stabilization of operant ethanol self-administration in male Wistar rats, dependence was induced in half the animals by subjecting them to a 4-week intermittent vapor exposure period in which animals were exposed to ethanol vapor for 14h/day. Subsequent to dependence induction, the effect of alpha1-noradrenergic receptor antagonist prazosin (0.0, 0.25, 0.5, 1, 1.5, and 2.0mg/kg IP) was tested on operant responding for ethanol in vapor-exposed and control rats during acute withdrawal. In ethanol-dependent animals, prazosin significantly suppressed responding at the 1.5 and 2.0mg/kg doses, whereas only the 2.0mg/kg dose was effective in nondependent animals, identifying an increase in the sensitivity to prazosin in dependent animals. Conversely, at the lowest dose tested (0.25mg/kg), prazosin increased responding in nondependent animals, which is consistent with the effect of anxiolytics on ethanol self-administration in nondependent animals. None of the doses tested reliably affected concurrent water self-administration. These results suggest the involvement of the noradrenergic system in the excessive alcohol drinking seen during acute withdrawal in ethanol-dependent rats. PMID:18358987

  9. Ethanol-nicotine interactions in long-sleep and short-sleep mice

    SciTech Connect

    de Fiebre, C.M.; Marks, M.J.; Collins, A.C. )

    1990-05-01

    The possibility that common genetic factors regulate initial sensitivities to ethanol and nicotine as well as the development of cross-tolerance between these agents was explored using the long-sleep (LS) and short-sleep (SS) mice. The LS mice proved to be more sensitive to an acute challenge with nicotine than were the SS mice. Segregation analysis (F1, F2, backcross) indicated that ethanol sensitivity and nicotine sensitivity segregate together. Acute pretreatment with nicotine did not significantly affect sensitivity to ethanol, but ethanol pretreatment altered nicotine responsiveness. The LS mice develop more tolerance to nicotine and ethanol than do the SS and they also develop more cross-tolerance. These genetically determined differences in initial sensitivities, and tolerance and cross-tolerance development are not readily explained by differences in brain nicotinic receptor numbers.

  10. Effects of embryonic ethanol exposure at low doses on neuronal development, voluntary ethanol consumption and related behaviors in larval and adult zebrafish: Role of hypothalamic orexigenic peptides.

    PubMed

    Sterling, M E; Chang, G-Q; Karatayev, O; Chang, S Y; Leibowitz, S F

    2016-05-01

    Embryonic exposure to ethanol is known to affect neurochemical systems in rodents and increase alcohol drinking and related behaviors in humans and rodents. With zebrafish emerging as a powerful tool for uncovering neural mechanisms of numerous diseases and exhibiting similarities to rodents, the present report building on our rat studies examined in zebrafish the effects of embryonic ethanol exposure on hypothalamic neurogenesis, expression of orexigenic neuropeptides, and voluntary ethanol consumption and locomotor behaviors in larval and adult zebrafish, and also effects of central neuropeptide injections on these behaviors affected by ethanol. At 24h post-fertilization, zebrafish embryos were exposed for 2h to ethanol, at low concentrations of 0.25% and 0.5%, in the tank water. Embryonic ethanol compared to control dose-dependently increased hypothalamic neurogenesis and the proliferation and expression of the orexigenic peptides, galanin (GAL) and orexin (OX), in the anterior hypothalamus. These changes in hypothalamic peptide neurons were accompanied by an increase in voluntary consumption of 10% ethanol-gelatin and in novelty-induced locomotor and exploratory behavior in adult zebrafish and locomotor activity in larvae. After intracerebroventricular injection, these peptides compared to vehicle had specific effects on these behaviors altered by ethanol, with GAL stimulating consumption of 10% ethanol-gelatin more than plain gelatin food and OX stimulating novelty-induced locomotor behavior while increasing intake of food and ethanol equally. These results, similar to those obtained in rats, suggest that the ethanol-induced increase in genesis and expression of these hypothalamic peptide neurons contribute to the behavioral changes induced by embryonic exposure to ethanol. PMID:26778786

  11. The effect of ethanol on temperature selection in the goldfish, Carassius auratus.

    PubMed

    O'Connor, C S; Crawshaw, L I; Bedichek, R C; Crabbe, J C

    1988-02-01

    The effect of ethanol on behavioral thermoregulation in the goldfish, Carassius auratus, was studied by adding ethanol to a horizontal aquatic temperature gradient which allowed each fish to select its preferred temperature within a range of about 9 degrees C to 33 degrees C. Alternating exposure to 1.0% (v/v) ethanol and water showed that fish (10 to 15 g) responded to ethanol by selecting lower temperatures. Onset and disappearance of the effect occurred within 10 min of exposure to or removal from ethanol. Fish exposed to 1.0% ethanol for 3 hr did not show acute tolerance. When fish were exposed to increasing concentrations of ethanol from 0.0% to 1.7%, the lowest concentration to elicit a response was 0.5% ethanol. The magnitude of the response plateaued at 0.7% ethanol. At this concentration and above, selected temperatures remained about 2 degrees C below temperatures selected by controls. Because thermoregulatory responses of fish are behavioral and relatively easy to observe and quantify, goldfish offer a useful model for the study of ethanol effects on central nervous system control of thermoregulation. Ethanol produces a prompt, stable, and reproducible depression of selected temperature by lowering the thermoregulatory set point in the goldfish. PMID:3362919

  12. Gene Expression Under the Influence: Transcriptional Profiling of Ethanol in the Brain

    PubMed Central

    Contet, Candice

    2013-01-01

    Sensitivity to ethanol intoxication, propensity to drink ethanol and vulnerability to develop alcoholism are all influenced by genetic factors. Conversely, exposure to ethanol or subsequent withdrawal produce gene expression changes, which, in combination with environmental variables, may participate in the emergence of compulsive drinking and relapse. The present review offers an integrated perspective on brain gene expression profiling in rodent models of predisposition to differential ethanol sensitivity or consumption, in rats and mice subjected to acute or chronic ethanol exposure, as well as in human alcoholics. The functional categories over-represented among differentially expressed genes suggest that the transcriptional effects of chronic ethanol consumption contribute to the neuroplasticity and neurotoxicity characteristic of alcoholism. Importantly, ethanol produces distinct transcriptional changes within the different brain regions involved in intoxication, reinforcement and addiction. Special emphasis is put on recent profiling studies that have provided some insights into the molecular mechanisms potentially mediating genome-wide regulation of gene expression by ethanol. In particular, current evidence for a role of transcription factors, chromatin remodeling and microRNAs in coordinating the expression of large sets of genes in animals predisposed to excessive ethanol drinking or exposed to protracted abstinence, as well as in human alcoholics, is presented. Finally, studies that have compared ethanol with other drugs of abuse have highlighted common gene expression patterns that may play a central role in drug addiction. The availability of novel technologies and a focus on mechanistic approaches are shaping the future of ethanol transcriptomics. PMID:24078902

  13. Hypothalamic peptides controlling alcohol intake: Differential effects on microstructure of drinking bouts

    PubMed Central

    Chen, Yu-Wei; Barson, Jessica R.; Chen, Aimee; Hoebel, Bartley G.; Leibowitz, Sarah F.

    2014-01-01

    Different alcohol drinking patterns, involving either small and frequent drinking bouts or large and long-lasting bouts, are found to differentially affect the risk for developing alcohol-related diseases, suggesting that they have different underlying mechanisms. Such mechanisms may involve orexigenic peptides known to stimulate alcohol intake through their actions in the hypothalamic paraventricular nucleus (PVN). These include orexin (OX), which is expressed in the perifornical lateral hypothalamus, and galanin (GAL) and enkephalin (ENK), which are expressed within as well as outside the PVN. To investigate the possibility that these peptides affect different aspects of consumption, a microstructural analysis of ethanol drinking behavior was performed in male, Sprague-Dawley rats trained to drink 7% ethanol and implanted with guide shafts aimed at the PVN. While housed in specialized cages containing computerized intake monitors (BioDAQ Laboratory Intake Monitoring System, Research Diets Inc., New Brunswick, NJ) that measure bouts of ethanol drinking, these rats were given PVN injections of OX (0.9 nmol), GAL (1.0 nmol), or the ENK analog D-Ala2-met-enkephalinamide (DALA) (14.2 nmol), as compared to saline vehicle. Results revealed clear differences between the effects of these peptides. While all 3 stimulated ethanol intake, they had distinct effects on patterns of drinking, with OX increasing the number of drinking bouts, GAL increasing the size of the drinking bouts, and DALA increasing both the size and duration of the bouts. In contrast, these peptides had little impact on water or food intake. These results support the idea that different peptides can increase ethanol consumption by promoting distinct aspects of the ethanol drinking response. The stimulatory effect of OX on drinking frequency may be related to its neuronally stimulatory properties, while the stimulatory effect of GAL and ENK on bout size and duration may reflect a suppressive effect of

  14. Hypothalamic peptides controlling alcohol intake: differential effects on microstructure of drinking bouts.

    PubMed

    Chen, Yu-Wei; Barson, Jessica R; Chen, Aimee; Hoebel, Bartley G; Leibowitz, Sarah F

    2014-11-01

    Different alcohol drinking patterns, involving either small and frequent drinking bouts or large and long-lasting bouts, are found to differentially affect the risk for developing alcohol-related diseases, suggesting that they have different underlying mechanisms. Such mechanisms may involve orexigenic peptides known to stimulate alcohol intake through their actions in the hypothalamic paraventricular nucleus (PVN). These include orexin (OX), which is expressed in the perifornical lateral hypothalamus, and galanin (GAL) and enkephalin (ENK), which are expressed within as well as outside the PVN. To investigate the possibility that these peptides affect different aspects of consumption, a microstructural analysis of ethanol drinking behavior was performed in male, Sprague-Dawley rats trained to drink 7% ethanol and implanted with guide shafts aimed at the PVN. While housed in specialized cages containing computerized intake monitors (BioDAQ Laboratory Intake Monitoring System, Research Diets Inc., New Brunswick, NJ) that measure bouts of ethanol drinking, these rats were given PVN injections of OX (0.9 nmol), GAL (1.0 nmol), or the ENK analog D-Ala2-met-enkephalinamide (DALA) (14.2 nmol), as compared to saline vehicle. Results revealed clear differences between the effects of these peptides. While all 3 stimulated ethanol intake, they had distinct effects on patterns of drinking, with OX increasing the number of drinking bouts, GAL increasing the size of the drinking bouts, and DALA increasing both the size and duration of the bouts. In contrast, these peptides had little impact on water or food intake. These results support the idea that different peptides can increase ethanol consumption by promoting distinct aspects of the ethanol drinking response. The stimulatory effect of OX on drinking frequency may be related to its neuronally stimulatory properties, while the stimulatory effect of GAL and ENK on bout size and duration may reflect a suppressive effect of

  15. Cerebroventricular tetrahydropapaveroline infusions and ethanol consumption in the rat.

    PubMed

    Sinclair, J D; Myers, R D

    1982-01-01

    Discrepant results have been reported from different laboratories on the effects of tetrahydropapaveroline (THP) and related compounds. In order to try to explore the discrepancy, an independent researcher participated in a partial replication attempt at the laboratory from which reports had previously come that THP markedly increased ethanol consumption by rats and produced withdrawal-like behavior. Withdrawal-like signs were observed after several once-daily bilateral ventricular infusions of 1.0 microgram THP. These abnormal behaviors varied in frequency and intensity but continued up to the last day of infusion and were rated independently by up to 5 judges. The mean ethanol intake, however, during THP treatment remained virtually the same as before THP (mean g ethanol per kg body wt. +/- SE: 1.60 +/- 0.29 before THP, 1.69 +/- 0.45 during THP). Control rats drank similar amounts of ethanol (1.60 +/- 0.33 before vehicle infusions, 1.65 +/- 0.42 during vehicle infusions). The individual THP animals tended to show greater variations than the controls from their own pre-treatment levels, but none of them showed a mean increase of greater than 2.0 g/kg in ethanol intake. Injections of THP or noreleagnine into cannulae aimed at hippocampal and periventricular grey sites also failed to increase alcohol drinking; however because histology was not available, it is not known whether or not the sites of injection were located in these structures. In comparison to the previously published report of Myers and Oblinger (25), this experiment differed in several variables. It is concluded that the precise experimental parameters necessary for once-daily THP reliably to increase ethanol consumption remain to be determined. PMID:6890240

  16. Oleanolic acid ethanol monosolvate

    PubMed Central

    Froelich, Anna; Gzella, Andrzej K.

    2010-01-01

    Crystals of the title compound (systematic name: 3β-hy­droxy­olean-12-en-28-oic acid ethanol monosolvate), C30H48O3·C2H5OH, were obtained from unsuccessful co-crystallization trials. The asymmetric unit contains two symmetry-independent oleanolic acid mol­ecules, as well as two ethanol solvent mol­ecules. Inter­molecular O—H⋯O hydrogen bonds stabilize the crystal packing. In the oleanolic acid mol­ecules, ring C has a slightly distorted envelope conformation, while rings A, B, D and E adopt chair conformations and rings D and E are cis-fused. Both independent ethanol mol­ecules are orientationally disordered [occupancy ratios of 0.742 (8):0.258 (8) and 0.632 (12):0.368 (12). PMID:21588987

  17. Effects of different concentrations of sugarcane alcohol on food intake and nutritional status of male and female periadolescent rats.

    PubMed

    Gonçalves de Orange, Luciana; Bion, Francisca Martins; Rolim de Lima, Cybelle

    2009-03-01

    The present study evaluated the effects of food and alcohol intake on the nutritional and metabolic status of male and female periadolescent rats submitted to single (15%) and multiple (10%, 20%, 30%) concentrations of hydroalcoholic solutions of sugar-based alcohol associated with a feed mixture. Thirty-six periadolescent Wistar rats were used and randomly arranged into three groups: Group A (control; 0% ethanol; six males and six females), Group B (15% ethanol; six males and six females), and Group C (10%, 20%, and 30% ethanol; six males and six females). Food consumption, body weight, water intake (mL), ethanol intake (g/kg/day), ethanol preference in relation to water and different concentrations, and serum biochemical dosages (glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, very low-density lipoprotein fraction, triglycerides, cholesterol/HDL [CT/HDL], albumin) were analyzed. Males from Group C ingested more feed than females, which consumed reducing amounts throughout the weeks studied. Males also had heavier body weight, which increased throughout the experimental period. The animals ingested more water (females ingested more than males) in the first experimental week. Group C had a higher ethanol intake and greater preference for ethanol over water in both genders than Group B, which decreased over the subsequent weeks. Serum glucose was lower in Group A, whereas the CT/HDL ratio was lower in Group C. These findings allow the conclusion that nutritional and metabolic impact resulting from alcohol intake is different between genders and between the different forms in which the drug is offered. It is important to warn the population about the concentrations of alcohol intake, which may influence the growth and development of adolescents, thereby compromising their quality of life. PMID:19251115

  18. Effects of ethanol ingestion on alpha-adrenoceptor-mediated circulatory responses in man.

    PubMed Central

    Eisenhofer, G; Lambie, D G; Johnson, R H

    1984-01-01

    The acute effects of ethanol on pressor responses to graded intravenous infusions of noradrenaline (24, 48, 90 ng kg-1 min-1) and methoxamine (0.2, 0.4, 0.8, 1.6, 2.0 mg/min, 1 min each) were each investigated in eight normal male subjects. The effects of ethanol on blood pressure, heart rate and plasma catecholamine responses to lower body negative pressure were also examined in six normal male subjects. Each subject acted as his own control by participating twice, once after consumption of ethanol (1.0 ml/kg, 20% v/v, in orange juice) and once after an equivalent volume of orange juice. Ethanol consumption significantly reduced the diastolic blood pressure response to infusion of noradrenaline. This occurred despite a significantly greater increase in plasma noradrenaline concentrations during infusion after ethanol. The systolic and diastolic blood pressure responses to infusion of methoxamine were both significantly reduced after ethanol. During lower body negative pressure, prior consumption of ethanol resulted in a greater fall in systolic blood pressure and a smaller rise in diastolic blood pressure. Plasma noradrenaline responses to lower body negative pressure were significantly increased after ethanol. It is concluded that acute ethanol ingestion depresses alpha-adrenoceptor-mediated vasoconstriction, with resulting impairment of blood pressure control. PMID:6091712

  19. Genetically determined differences in ethanol sensitivity influenced by body temperature during intoxication

    SciTech Connect

    Alkana, R.L.; Finn, D.A.; Bejanian, M.; Crabbe, J.C.

    1988-01-01

    The present study investigated the importance of body temperature during intoxication in mediating differences between five inbred strains of mice (C57BL/6J; BALB/cJ; DBA/2J; A/HeJ; 129/J) in their acute sensitivity to the hypnotic effects of ethanol. Mice exposed to 22/degrees/C after ethanol injection became hypothermic and exhibited statistically significant differences between strains in rectal temperatures at the return of the righting reflex (RORR), duration of loss of the righting reflex (LORR), and blood and brain ethanol concentrations at RORR. Exposure to 34/degrees/C after injection offset ethanol-hypothermia and markedly reduced strain-related differences in rectal temperatures and blood and brain ethanol concentrations at RORR. Brain ethanol concentrations at RORR were significantly lower in C57, BALB, DBA and A/He mice exposed to 34/degrees/C compared to mice exposed to 22/degrees/C during intoxication suggesting that offsetting hypothermia increased ethanol sensitivity in these strains. Taken with previous in vitro studies, these results suggest that genetically determined differences in acute sensitivity to the behavioral effects of ethanol reflect differences in body temperature during intoxication as well as differences in sensitivity to the initial actions of ethanol at the cellular level.

  20. Decreased sensitivity to the hypnotic effects of ethanol early in ontogeny.

    PubMed

    Silveri, M M; Spear, L P

    1998-05-01

    Sensitivity to the hypnotic effects of ethanol was examined in Sprague-Dawley male and female rats at 16, 26, 36, 46, 56, or 96 days postnatally. Following administration of 3.5, 4.0, 4.5, or 5.0 g/kg of a 17% v/v ethanol solution, sleep times were recorded and blood alcohol levels (BALs) and brain alcohol levels (BrALs) were measured upon awakening. In addition to examining ethanol sleep time during ontogeny, data were used to estimate acute tolerance (indexed by the slope of the linear regressions of waking BALs and BrALs as a function of dose) and initial brain sensitivity to ethanol (indexed by calculating the y-intercept from the linear regression of BrALs as a function of sleep time). The results showed a marked increase in sensitivity to ethanol hypnosis during ontogeny, with young animals exhibiting shorter ethanol-induced sleep times and high waking BALs and BrALs. This ontogenetic increase in ethanol sensitivity was associated with a developmental decline in acute tolerance, with acute tolerance being most pronounced at postnatal day (P) 16 and evident only up to P36. Initial sensitivity conversely increased with age, with P16 pups showing lower initial brain sensitivity to ethanol than at all other ages. Gender differences emerged in adulthood, with males sleeping significantly longer than females at P56 and P96. These findings suggest that the marked insensitivity of young animals to the hypnotic effects of ethanol is related to both pronounced acute tolerance, as well as reduced initial brain sensitivity to ethanol early in life. PMID:9622449

  1. Ethanol from sweet sorghum

    SciTech Connect

    Polack, J.A.; Day, D,F.

    1980-08-01

    Sweet sorghum has long been of interest to sugar farmers and sugar processors. The thought has been that one could plant the sweet sorghum on fallow land and harvest it and process it in September, before the start of the regular sugar cane griding season. Several disadvantages have prevented its use in sugar production, but these seem much less of a problem if ethanol is to be produced. The DOE has targeted sweet sorghum as a prime crop for ethanol production, and the planting of 14 million new acres in sweet sorghum is the underlying assumption in a DOE plant to produce 11 billion gallons of alcohol fuel by the year 2000.

  2. Ethanol Reversal of Cellular Tolerance to Morphine in Rat Locus Coeruleus Neurons

    PubMed Central

    Llorente, Javier; Withey, Sarah; Rivero, Guadalupe; Cunningham, Margaret; Cooke, Alex; Saxena, Kunal; McPherson, Jamie; Oldfield, Sue; Dewey, William L.; Bailey, Chris P.; Kelly, Eamonn; Henderson, Graeme

    2013-01-01

    Consumption of ethanol is a considerable risk factor for death in heroin overdose. We sought to determine whether a mildly intoxicating concentration of ethanol could alter morphine tolerance at the cellular level. In rat locus coeruleus (LC) neurons, tolerance to morphine was reversed by acute exposure of the brain slice to ethanol (20 mM). Tolerance to the opioid peptide [d-Ala2,N-MePhe4,Gly-ol]-enkephalin was not reversed by ethanol. Previous studies in LC neurons have revealed a role for protein kinase C (PKC)α in μ-opioid receptor (MOPr) desensitization by morphine and in the induction and maintenance of morphine tolerance, but we have been unable to demonstrate that 20 mM ethanol produces significant inhibition of PKCα. The ability of ethanol to reverse cellular tolerance to morphine in LC neurons was absent in the presence of the phosphatase inhibitor okadaic acid, indicating that dephosphorylation is involved. In human embryonic kidney 293 cells expressing the MOPr, ethanol reduced the level of MOPr phosphorylation induced by morphine. Ethanol reversal of tolerance did not appear to result from a direct effect on MOPr since acute exposure to ethanol (20 mM) did not modify the affinity of binding of morphine to the MOPr or the efficacy of morphine for G-protein activation as measured by guanosine 5′-O-(3-[35S]thio)triphosphate binding. Similarly, ethanol did not affect MOPr trafficking. We conclude that acute exposure to ethanol enhances the effects of morphine by reversing the processes underlying morphine cellular tolerance. PMID:23716621

  3. POROUS DIKE INTAKE EVALUATION

    EPA Science Inventory

    The report gives results of an evaluation of a porous dike intake. A small-scale test facility was constructed and continuously operated for 2 years under field conditions. Two stone dikes of gabion construction were tested: one consisted of 7.5 cm stones; and the other, 20 cm st...

  4. Ethanol Impacts on BTEX Plumes

    EPA Science Inventory

    The impacts of ethanol on benzene, toluene, ethylbenzene and xylenes (BTEX) are beginning to become established through laboratory, modeling and field research. Usage of ethanol, which increased due to federal mandates, drives interest and potential impacts on BTEX. Through co...

  5. Effects of prenatal and postnatal maternal ethanol on offspring response to alcohol and psychostimulants in long evans rats.

    PubMed

    Barbier, E; Houchi, H; Warnault, V; Pierrefiche, O; Daoust, M; Naassila, M

    2009-06-30

    An important factor that may influence addiction liability is exposure during the early life period. Exposure to ethanol, early in life, can have long-lasting implications on brain function and drugs of abuse response later in life. In the present study we investigated the behavioral responses to ethanol and to psychostimulants in Long Evans rats that have been exposed to pre- and postnatal ethanol. Since a relationship between heightened drug intake and susceptibility to drug-induced locomotor activity/sensitization has been demonstrated, we tested these behavioral responses, in control and early life ethanol-exposed animals. The young adult male and female progeny were tested for locomotor response to alcohol, cocaine and d-amphetamine. Sedative, rewarding effects of alcohol and alcohol consumption were measured. Our results show that early life ethanol exposure behaviorally sensitized animals to subsequent ethanol and psychostimulants exposure. Ethanol-exposed animals were also more sensitive to the hyperlocomotor effects of all drugs of abuse tested and to those of the dopamine receptor agonist apomorphine. Locomotor sensitization to repeated injections of cocaine was facilitated in ethanol-exposed animals. Ethanol-induced conditioned place preference was also facilitated in ethanol-exposed animals. Ethanol consumption and preference were increased after early life ethanol exposure and this was associated with decreased sensitivity to the sedative effects of ethanol. The altered behavioral responses to drugs of abuse were associated with decreased striatal dopamine transporter and hippocampal NMDAR binding. Our results outline an increased vulnerability to rewarding and stimulant effects of ethanol and psychostimulants and support the epidemiological and clinical data that suggested that early chronic exposure to ethanol may increase the propensity for later self-administration of ethanol or other substances. PMID:19348874

  6. Peptides and food intake.

    PubMed

    Sobrino Crespo, Carmen; Perianes Cachero, Aránzazu; Puebla Jiménez, Lilian; Barrios, Vicente; Arilla Ferreiro, Eduardo

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the regulation of food intake and energy homeostasis. Nutrients generated by food digestion have been proposed to activate G-protein-coupled receptors on the luminal side of enteroendocrine cells, e.g., the L-cells. This stimulates the release of gut hormones into the circulation such as glucagon-like peptide-1 (GLP-1), oxyntomodulin, pancreatic polypeptides, peptide tyrosine tyrosine, and cholecystokinin, which inhibit appetite. Ghrelin is a peptide secreted from the stomach and, in contrast to other gut hormones, plasma levels decrease after a meal and potently stimulate food intake. Other circulating factors such as insulin and leptin relay information regarding long-term energy stores. Both hormones circulate at proportional levels to body fat content, enter the CNS proportionally to their plasma levels, and reduce food intake. Circulating hormones can influence the activity of the arcuate nucleus (ARC) neurons of the hypothalamus, after passing across the median eminence. Circulating factors such as gut hormones may also influence the nucleus of the tractus solitarius (NTS) through the adjacent circumventricular organ. On the other hand, gastrointestinal vagal afferents converge in the NTS of the brainstem. Neural projections from the NTS, in turn, carry signals to the hypothalamus. The ARC acts as an integrative center, with two major subpopulations of neurons influencing appetite, one of them coexpressing neuropeptide Y and agouti-related protein (AgRP) that increases food

  7. Peptides and Food Intake

    PubMed Central

    Sobrino Crespo, Carmen; Perianes Cachero, Aránzazu; Puebla Jiménez, Lilian; Barrios, Vicente; Arilla Ferreiro, Eduardo

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the regulation of food intake and energy homeostasis. Nutrients generated by food digestion have been proposed to activate G-protein-coupled receptors on the luminal side of enteroendocrine cells, e.g., the L-cells. This stimulates the release of gut hormones into the circulation such as glucagon-like peptide-1 (GLP-1), oxyntomodulin, pancreatic polypeptides, peptide tyrosine tyrosine, and cholecystokinin, which inhibit appetite. Ghrelin is a peptide secreted from the stomach and, in contrast to other gut hormones, plasma levels decrease after a meal and potently stimulate food intake. Other circulating factors such as insulin and leptin relay information regarding long-term energy stores. Both hormones circulate at proportional levels to body fat content, enter the CNS proportionally to their plasma levels, and reduce food intake. Circulating hormones can influence the activity of the arcuate nucleus (ARC) neurons of the hypothalamus, after passing across the median eminence. Circulating factors such as gut hormones may also influence the nucleus of the tractus solitarius (NTS) through the adjacent circumventricular organ. On the other hand, gastrointestinal vagal afferents converge in the NTS of the brainstem. Neural projections from the NTS, in turn, carry signals to the hypothalamus. The ARC acts as an integrative center, with two major subpopulations of neurons influencing appetite, one of them coexpressing neuropeptide Y and agouti-related protein (AgRP) that increases food

  8. Turning Rate Dynamics of Zebrafish Exposed to Ethanol

    NASA Astrophysics Data System (ADS)

    Mwaffo, Violet; Porfiri, Maurizio

    2015-06-01

    Zebrafish is emerging as a species of choice in alcohol-related pharmacological studies. In these studies, zebrafish are often exposed to acute ethanol treatments and their activity scored during behavioral assays. Computational modeling of zebrafish behavior is expected to positively impact these efforts by offering a predictive toolbox to plan hypothesis-driven studies, reduce the number of subjects, perform pilot trials, and refine behavioral screening. In this work, we demonstrate the use of the recently proposed jump persistent turning walker to model the turning rate dynamics of zebrafish exposed to acute ethanol administration. This modeling framework is based on a stochastic mean reverting jump process to capture the sudden and large changes in orientation of swimming zebrafish. The model is calibrated on an available experimental dataset of 40 subjects, tested at different ethanol concentrations. We demonstrate that model parameters are modulated by ethanol administration, whereby both the relaxation rate and jump frequency of the turning rate dynamics are influenced by ethanol concentration. This effort offers a first evidence for the possibility of complementing zebrafish pharmacological research with computational modeling of animal behavior.

  9. Acute Hepatic Porphyria

    PubMed Central

    Bissell, D. Montgomery; Wang, Bruce

    2015-01-01

    The porphyrias comprise a set of diseases, each representing an individual defect in one of the eight enzymes mediating the pathway of heme synthesis. The diseases are genetically distinct but have in common the overproduction of heme precursors. In the case of the acute (neurologic) porphyrias, the cause of symptoms appears to be overproduction of a neurotoxic precursor. For the cutaneous porphyrias, it is photosensitizing porphyrins. Some types have both acute and cutaneous manifestations. The clinical presentation of acute porphyria consists of abdominal pain, nausea, and occasionally seizures. Only a small minority of those who carry a mutation for acute porphyria have pain attacks. The triggers for an acute attack encompass certain medications and severely decreased caloric intake. The propensity of females to acute attacks has been linked to internal changes in ovarian physiology. Symptoms are accompanied by large increases in delta-aminolevulinic acid and porphobilinogen in plasma and urine. Treatment of an acute attack centers initially on pain relief and elimination of inducing factors such as medications; glucose is administered to reverse the fasting state. The only specific treatment is administration of intravenous hemin. An important goal of treatment is preventing progression of the symptoms to a neurological crisis. Patients who progress despite hemin administration have undergone liver transplantation with complete resolution of symptoms. A current issue is the unavailability of a rapid test for urine porphobilinogen in the urgent-care setting. PMID:26357631

  10. Effect of pimozide on home cage ethanol drinking in the rat: dependence on drinking session length.

    PubMed

    Pfeffer, A O; Samson, H H

    1986-05-01

    A stimulus-fading procedure was used to initiate ethanol drinking in free-feeding Long Evans rats. During daily half-hour drinking sessions in the home cage, a combination of sucrose and ethanol was first presented to the rats; gradually the sucrose concentration was reduced and the ethanol concentration increased until after 7 weeks the rats were drinking 10% ethanol with no sucrose. After stabilization of intake, either pimozide (PIM, 0.25, 0.50 and 1.00 mg/kg) was injected 4 h before drinking sessions or (d)-amphetamine (DEX, 0.25 and 0.50 mg/kg) was injected 15 min before sessions. The 0.50 and 1.00 mg/kg PIM doses and the 0.50 DEX dose significantly reduced intake compared to vehicle injections. In the second part of the experiment, the rats were given 24-h access to 10% ethanol and water in a two-bottle choice procedure. In this condition, 0.50 mg/kg PIM failed to reduce intake compared to vehicle. The critical difference between the two procedures seems to be that with the 30-min sessions, PIM injections were timed to have their maximal effect during testing. With 24-h sessions, decreases in intake produced by PIM could have been compensated for by increases after the drug had worn off. The hypothesis that dopamine is necessary for ethanol reinforcement receives support from the PIM effect on the 30-min sessions. The DEX effect extends the generality of our previous finding that DEX reduces ethanol-reinforced lever pressing in free-feeding rats. PMID:3720531

  11. Binge Ethanol and Liver: New Molecular Developments

    PubMed Central

    Shukla, Shivendra D.; Pruett, Stephen B.; Szabo, Gyongyi; Arteel, Gavin E.

    2016-01-01

    Binge consumption of alcohol is an alarming global health problem. Binge (acute) ethanol (EtOH) is implicated in the pathophysiology of alcoholic liver disease (ALD). New studies from experimental animals and from humans indicate that binge EtOH has profound effects on immunological, signaling, and epigenetic parameters of the liver. This is in addition to the known metabolic effects of acute EtOH. Binge EtOH alters the levels of several cellular components and dramatically amplifies liver injury in chronically EtOH exposed liver. These studies highlight the importance of molecular investigations into binge effects of EtOH for a better understanding of ALD and also to develop therapeutic strategies to control it. This review summarizes these recent developments. PMID:23347137

  12. Bidirectional enantioselective effects of the GABAB receptor agonist baclofen in two mouse models of excessive ethanol consumption

    PubMed Central

    Kasten, Chelsea R.; Blasingame, Shelby N.; Boehm, Stephen L.

    2014-01-01

    The GABAB receptor agonist baclofen has been studied extensively in preclinical models of alcohol use disorders, yet results on its efficacy have been uncertain. Racemic baclofen, which is used clinically, can be broken down into separate enantiomers of the drug. Baclofen has been shown to produce enantioselective effects in behavioral assays including those modeling reflexive and sexual behavior. The current studies sought to characterize the enantioselective effects of baclofen in two separate models of ethanol consumption. The first was a Drinking-in-the-Dark procedure that provides “binge-like” ethanol access to mice by restricting access to a two hour period, three hours into the dark cycle. The second was a two-bottle choice procedure that utilized selectively bred High Alcohol Preferring 1 (HAP1) mice to model chronic ethanol access. HAP1 mice are selectively bred to consume pharmacologically relevant amounts of ethanol in a 24-hour two-bottle choice paradigm. The results showed that baclofen yields enantioselective effects on ethanol intake in both models, and that these effects are bidirectional. Total ethanol intake was decreased by R(+)- baclofen, while total intake was increased by S(-)-baclofen in the binge-like and chronic drinking models. Whereas overall binge-like saccharin intake was significantly reduced by R(+)- baclofen, chronic intake was not significantly altered. S(-)- baclofen did not significantly alter saccharin intake. Neither enantiomer significantly affected locomotion during binge-like reinforcer consumption. Collectively, these results demonstrate that baclofen produces enantioselective effects on ethanol consumption. More importantly, the modulation of consumption is bidirectional. The opposing enantioselective effects may explain some of the variance seen in published baclofen literature. PMID:25557834

  13. Bidirectional enantioselective effects of the GABAB receptor agonist baclofen in two mouse models of excessive ethanol consumption.

    PubMed

    Kasten, Chelsea R; Blasingame, Shelby N; Boehm, Stephen L

    2015-02-01

    The GABAB receptor agonist baclofen has been studied extensively in preclinical models of alcohol-use disorders, yet results on its efficacy have been uncertain. Racemic baclofen, which is used clinically, can be broken down into separate enantiomers of the drug. Baclofen has been shown to produce enantioselective effects in behavioral assays, including those modeling reflexive and sexual behavior. The current studies sought to characterize the enantioselective effects of baclofen in two separate models of ethanol consumption. The first was a Drinking-in-the-Dark procedure that provides "binge-like" ethanol access to mice by restricting access to a 2-h period, 3 h into the dark cycle. The second was a two-bottle choice procedure that utilized selectively bred High Alcohol Preferring 1 (HAP1) mice to model chronic ethanol access. HAP1 mice are selectively bred to consume pharmacologically relevant amounts of ethanol in a 24-h two-bottle choice paradigm. The results showed that baclofen yields enantioselective effects on ethanol intake in both models, and that these effects are bidirectional. Total ethanol intake was decreased by R(+)-baclofen, while total intake was increased by S(-)-baclofen in the binge-like and chronic drinking models. Whereas overall binge-like saccharin intake was significantly reduced by R(+)-baclofen, chronic intake was not significantly altered. S(-)-baclofen did not significantly alter saccharin intake. Neither enantiomer significantly affected locomotion during binge-like reinforcer consumption. Collectively, these results demonstrate that baclofen produces enantioselective effects on ethanol consumption. More importantly, the modulation of consumption is bidirectional. The opposing enantioselective effects may explain some of the variance seen in published baclofen literature. PMID:25557834

  14. Ethanol reduces evoked dopamine release and slows clearance in the rat medial prefrontal cortex

    PubMed Central

    Shnitko, Tatiana A.; Kennerly, Laura C.; Spear, Linda P.; Robinson, Donita L.

    2014-01-01

    Background Ethanol intoxication affects cognitive performance, contributing to attentional deficits and poor decision making, which may occur via actions in the medial prefrontal cortex (mPFC). mPFC function is modulated by the catecholamines dopamine and norepinephrine. In this study, we examine the acute effects of ethanol on electrically-evoked dopamine release and clearance in the mPFC of anaesthetized rats naïve to alcohol or chronically exposed to alcohol during adolescence. Methods Dopamine release and clearance was evoked by electrical stimulation of the VTA and measured in the mPFC of anaesthetized rats with fast-scan cyclic voltammetry. In Experiments 1 and 2, effects of a high dose of ethanol (4g/kg, i.p.) on dopamine neurotransmission in the mPFC of ethanol-naïve rats and rats given ethanol exposure during adolescence were investigated. Effects of cumulative dosing of ethanol (0.5–4g/kg) on the dopamine release and clearance were investigated in Experiment 3. Experiment 4 studied effects of ethanol locally applied to the ventral tegmental area (VTA) on the dopamine neurotransmission in the mPFC of ethanol-naïve rats. Results A high dose of ethanol decreased evoked dopamine release within 10 min of administration in ethanol-naïve rats. When tested via cumulative dosing from 0.5–4g/kg, both 2 and 4g/kg ethanol inhibited evoked dopamine release in the mPFC of ethanol-naïve rats, while 4g/kg ethanol also slowed dopamine clearance. A similar effect on electrically-evoked dopamine release in the mPFC was observed after infusion of ethanol into the VTA. Interestingly, intermittent ethanol exposure during adolescence had no effect on observed changes in mPFC dopamine release and clearance induced by acute ethanol administration. Conclusions Taken together, these data describe ethanol-induced reductions in the dynamics of VTA-evoked mPFC dopamine release and clearance, with the VTA contributing to the attenuation of evoked mPFC dopamine release induced

  15. Modeling binge-like ethanol drinking by peri-adolescent and adult P rats

    PubMed Central

    Bell, Richard L.; Rodd, Zachary A.; Smith, Rebecca J.; Toalston, Jamie E.; Franklin, Kelle M.; McBride, William J.

    2011-01-01

    Alcohol binge-drinking, especially among adolescents and young adults, is a serious public health concern. The present study examined ethanol binge-like drinking by peri-adolescent [postnatal days (PNDs 30—72)] and adult (PNDs 90—132) alcohol-preferring (P) rats with a drinking-in-the-dark—multiple-scheduled-acces (DID-MSA) procedure used by our laboratory. Male and female P rats were provided concurrent access to 15% and 30% ethanol for three 1-hr sessions across the dark cycle 5 days/week. For the 1st week, adolescent and adult female P rats consumed 3.4 and 1.6 g/kg of ethanol, respectively, during the 1st hr of access, whereas for male rats the values were 3.5 and 1.1 g/kg of ethanol, respectively. Adult intakes increased to ~2.0 g/kg/hr and adolescent intakes decreased to ~2.5 g/kg/hr across the 6 weeks of ethanol access. The daily ethanol intake of adult DID-MSA rats approximated or modestly exceeded that seen in continuous access (CA) rats or the selection criterion for P rats (≥ 5g/kg/day). However, in general, the daily ethanol intake of DID-MSA peri-adolescent rats significantly exceeded that of their CA counterparts. BELs were assessed at 15-min intervals across the 3rd hr of access during the 4th week. Ethanol intake was 1.7 g/kg vs. 2.7 g/kg and BELs were 57 mg% vs. 100 mg% at 15- and 60-min, respectively. Intoxication induced by DID-MSA in female P rats was assessed during the 1st vs. 4th week of ethanol access. Level of impairment did not differ between the 2 weeks (106 vs. 97 sec latency to fall, 120 sec criterion) and was significant (vs. naïve controls) only during the 4th week. Overall, these findings support the use of the DID-MSA procedure in rats, and underscore the presence of age- and sex-dependent effects mediating ethanol binge-like drinking in P rats. PMID:21824488

  16. Ethanol Myths Fact Sheet

    SciTech Connect

    2009-10-27

    Ethanol is a clean, renewable fuel that is helping to reduce our nation’s dependence on oil and can offer additional economic and environmental benefits in the future. This fact sheet is intended to address some common misconceptions about this important alternative fuel.

  17. Sorghum to Ethanol Research

    SciTech Connect

    Jeff Dahlberg, Ph D; Ed Wolfrum, Ph D

    2010-06-30

    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 feed 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 help

  18. Sorghum to Ethanol Research

    SciTech Connect

    Dahlberg, Jeff; Wolfrum, Ed

    2010-06-30

    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 feed 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 help

  19. Ethanol Induction of CYP2A5: Role of CYP2E1-ROS-Nrf2 Pathway

    PubMed Central

    Lu, Yongke; Zhang, Xu Hannah

    2012-01-01

    Chronic ethanol consumption was previously shown to induce CYP2A5 in mice, and this induction of CYP2A5 by ethanol was CYP2E1 dependent. In this study, the mechanisms of CYP2E1-dependent ethanol induction of CYP2A5 were investigated. CYP2E1 was induced by chronic ethanol consumption to the same degree in wild-type (WT) mice and CYP2A5 knockout (Cyp2a5 –/–) mice, suggesting that unlike the CYP2E1-dependent ethanol induction of CYP2A5, ethanol induction of CYP2E1 is not CYP2A5 dependent. Microsomal ethanol oxidation was about 25% lower in Cyp2a5 –/– mice compared with that in WT mice, suggesting that CYP2A5 can oxidize ethanol although to a lesser extent than CYP2E1 does. CYP2A5 was induced by short-term ethanol consumption in human CYP2E1 transgenic knockin (Cyp2e1 –/– KI) mice but not in CYP2E1 knockout (Cyp2e1 –/–) mice. The redox-sensitive transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) was also induced by acute ethanol in Cyp2e1 –/– KI mice but not in Cyp2e1 –/– mice. Ethanol induction of CYP2A5 in Nrf2 knockout (Nrf2 –/–) mice was lower compared with that in WT mice, whereas CYP2E1 induction by ethanol was comparable in WT and Nrf2 –/– mice. Antioxidants (N-acetyl-cysteine and vitamin C), which blocked oxidative stress induced by chronic ethanol in WT mice and acute ethanol in Cyp2e1 –/– KI mice, also blunted the induction of CYP2A5 and Nrf2 by ethanol but not the induction of CYP2E1 by ethanol. These results suggest that oxidative stress induced by ethanol via induction of CYP2E1 upregulates Nrf2 activity, which in turn regulates ethanol induction of CYP2A5. Results obtained from primary hepatocytes, mice gavaged with binge ethanol or fed chronic ethanol, show that Nrf2-regulated ethanol induction of CYP2A5 protects against ethanol-induced steatosis. PMID:22552773

  20. Brain glucose content in fetuses of ethanol-fed rats

    SciTech Connect

    Pullen, G.; Singh, S.P.; Snyder, A.K.; Hoffen, B.

    1986-03-01

    The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4 and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.

  1. Effect of chronic ethanol administration on disposition of ethanol and its metabolites in rat.

    PubMed

    Kozawa, Shuji; Yukawa, Nobuhiro; Liu, Jinyao; Shimamoto, Akiko; Kakizaki, Eiji; Fujimiya, Tatsuya

    2007-03-01

    We studied the effects of chronic alcohol intake on the disposition of alcohol and its metabolites in the rat. We used male Wistar rats for all of the experiments in this study. Using a pair-feeding process, rats were fed a liquid diet containing alcohol or without alcohol for 6 weeks. Ethanol solutions (0.5, 1.0, 1.5, and 2.0 g/kg body weight [BW]) were administered as a bolus, intravenously. We then measured blood ethanol and acetate concentrations. Simultaneous multiline fitting was performed using mean blood alcohol concentration (BAC)-time curves fitted to the one-compartment open model with parallel first-order and Michaelis-Menten elimination kinetics. At low doses (0.5, 1.0, and 1.5 g/kgBW), no differences were observed between the alcohol group and the control group with respect to ethanol elimination rate, area under the curve of ethanol (AUC(EtOH)), and mean residence time of ethanol (MRT(EtOH)). At higher doses (2.0 g/kgBW), ethanol elimination rate in the alcohol group was significantly higher than in the control group (P<.5%). These findings were also substantiated by corresponding changes in AUC(EtOH) and MRT(EtOH). At low doses, no differences were observed between the alcohol group and the control group with respect to plateau concentration of acetate (AcT) (concentration of steady state=C(ss)AcT), area under the curve of AcT (AUC(AcT)), and mean residence time of AcT (MRT(AcT)). However, at higher doses, although there were no differences in C(ss)AcT, both AUC(AcT) and MRT(AcT) were significantly lower in the alcohol group when compared to the control group (P<.5%). Chronic alcohol consumption increases ethanol oxidation and AcT metabolism in rats, as observed at high blood alcohol concentrations (BACs). These effects were observed at BACs of 3.5-4.5 mg/ml, and were not observed at lower doses. Thus, with general alcohol consumption, interindividual differences and intra-individual changes in alcohol metabolism may not take into account increased

  2. Adenosinergic regulation of binge-like ethanol drinking and associated locomotor effects in male C57BL/6J mice

    PubMed Central

    Fritz, Brandon M; Boehm, Stephen L

    2015-01-01

    We recently observed that the addition of caffeine (a nonselective adenosine receptor antagonist) to a 20% ethanol solution significantly altered the intoxication profile of male C57BL/6J (B6) mice induced by voluntary binge-like consumption in the ‘Drinking-in-the-Dark’ (DID) paradigm. In the current study, the roles of A1 and A2A adenosine receptor subtypes, specifically, in binge-like ethanol consumption and associated locomotor effects were explored. Adult male B6 mice (PND 60-70) were allowed to consume 20% ethanol (v/v) or 2% sucrose (w/v) for 6 days via DID. On day 7, mice received a systemic administration (i.p.) of the A1 antagonist DPCPX (1, 3, 6 mg/kg), the A2A antagonist MSX-3 (1, 2, 4 mg/kg), or vehicle immediately prior to fluid access in DID. Antagonism of the A1 receptor via DPCPX was found to dose-dependently decrease binge-like ethanol intake and associated blood ethanol concentrations (p’s < 0.05), although no effect was observed on sucrose intake. Antagonism of A2A had no effect on ethanol or sucrose consumption, however, MSX-3 elicited robust locomotor stimulation in mice consuming either solution (p’s < 0.05). Together, these findings suggest unique roles for the A1 and A2A adenosine receptor subtypes in binge-like ethanol intake and its associated locomotor effects. PMID:26033424

  3. Ethanol-induced dysfunction of hepatocytes and leukocytes in patients without liver failure.

    PubMed

    Gheorghiu, Mihaela; Bâră, C; Păsărică, Daniela; Braşoveanu, Lorelei; Bleotu, Coralia; Topârceanu, Florica; Trandafir, T; Diaconu, Carmen C

    2004-01-01

    The repeated intake of a great amount of ethanol is followed by functional and organic changes in the body. The intestinal absorption of alcohol is accompanied by an increased absorption of Gram negative bacteria endotoxins in the portal blood. In the liver, endotoxins stimulate CD14 receptors on the membrane of Kupffer cells, with a secondary inflammatory liver response, consisting in the secretion of proinflammatory cytokines and acute phase proteins. Simultaneously, alcohol metabolism in the hepatocytes by alcohol dehydrogenase, microsomal enzymes and catalase pathways determines a large production of ROS (reactive oxygen species), with secondary oxidative aggression on all liver cells: hepatocytes, Kupffer cells, endothelial sinusoidal cells, hepatic stellate cells and liver s lymphocytes. The oxidative aggression, as well as the intermediary products of the alcohol metabolism, cause a structural change of the antigenic structures of the liver and of the released proteins, that induces an immune response on the both pathways (humoral and cellular). The pathophysiological mechanisms and the paraclinical characteristics of the ethanol-induced liver failure are well known, so we were interested to study the patients with chronic alcoholism, but no clinical or paraclinical sign of liver failure, in order to describe the liver's protective mechanisms. For this reason, 153 patients with chronic alcoholism were divided into four test lots, in order to determine: the activity and the serum level of ceruloplasmin, plasma level of MDA (malondialdehyde), lactic and pyruvic acids, serum level of transferrin, alpha1-antitrypsin, CRP (C reactive protein), C3 fraction of the complement, IgA, IgG, IgM, IL-1beta, IL-6 and IL-8, cytosolic level of the cytochrome c in the circulating leukocytes. An immunophenotype study (as normal markers) on the peripheral blood lymphocytes was performed, too. The results demonstrate an important oxidative aggression induced by three sources

  4. Ethanol and psychotropic drug interaction during pregnancy and lactation.

    PubMed

    Rawat, A K

    1981-09-01

    Prolonged maternal ethanol consumption for 8 days during pregnancy or for five days immediately after birth resulted in 30-46 per cent inhibition in the rate of chlorpromazine metabolism by the rat fetal and neonatal livers respectively. A significant increase in hepatic NADH/NAD and UDPG/UDPGA ratios was observed in suckling neonatal and maternal livers from the ethanol-fed group. Acute administration of ethanol with chlorpromazine led to about 60 per cent inhibition of the metabolism of chlorpromazine. This inhibitory effect of ethanol on the metabolism of chlorpromazine was largely abolished by preincubation of liver homogenates with pyrazole (2 mM). Lactate (10 mM) addition to liver homogenates resulted in a significant inhibition of chlorpromazine metabolism. It is suggested that maternal ethanol consumption during preganancy and lactation inhibits the hepatic metabolism of drugs such as chlorpromazine which require glucuronidation for their detoxification. This ethanol-mediated inhibition is largely exerted through the decrease in the NAD-dependent conversion of UDP-glucose (UDPG) to UDP-glucuronic acid, (UDPGA). PMID:21043245

  5. Alcohol intake alters immune responses and promotes CNS viral persistence in mice.

    PubMed

    Loftis, Jennifer M; Taylor, Jonathan; Raué, Hans-Peter; Slifka, Mark K; Huang, Elaine

    2016-10-01

    Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. PMID:27269869

  6. Estradiol valerate and alcohol intake: dose-response assessments

    PubMed Central

    Quirarte, Gina L; Reid, Larry D; de la Teja, I Sofía Ledesma; Reid, Meta L; Sánchez, Marco A; Díaz-Trujillo, Arnulfo; Aguilar-Vazquez, Azucena; Prado-Alcalá, Roberto A

    2007-01-01

    Background An injection of estradiol valerate (EV) provides estradiol for a prolonged period. Recent research indicates that a single 2.0 mg injection of EV modifies a female rat's appetite for alcoholic beverages. This research extends the initial research by assessing 8 doses of EV (from .001 to 2.0 mg/female rat), as well assessing the effects of 2.0 mg EV in females with ovariectomies. Results With the administration of EV, there was a dose-related loss of bodyweight reaching the maximum loss, when it occurred, at about 4 days after injections. Subsequently, rats returned to gaining weight regularly. Of the doses tested, only the 2.0 mg dose produced a consistent increase in intake of ethanol during the time previous research indicated that the rats would show enhanced intakes. There was, however, a dose-related trend for smaller doses to enhance intakes. Rats with ovariectomies showed a similar pattern of effects, to intact rats, with the 2 mg dose. After extensive histories of intake of alcohol, both placebo and EV-treated females had estradiol levels below the average measured in females without a history of alcohol-intake. Conclusion The data support the conclusion that pharmacological doses of estradiol can produce enduring changes that are manifest as an enhanced appetite for alcoholic beverages. The effect can occur among females without ovaries. PMID:17335585

  7. Effect of naloxone on behavioral changes induced by subchronic administration of ethanol in rats.

    PubMed

    Alvarez, C; Prunell, M; Boada, J

    1998-04-01

    Endogenous opioid peptides appear to be involved in acute behavioral effects induced by single doses of ethanol. However, its role in repeated ethanol exposure has not been studied. In the present study ethanol was given to rats at the doses of 2 and 4 g/kg by a stomach gauge for 15 days, and its effects on spontaneous motility, open-field activity, and active avoidance behavior recorded on the 3rd, the 6th and the 15th days. Then the effect of naloxone (0.5 and 2 mg/kg by intraperitoneal route) was tested against a challenge ethanol dose, administrated by oral route, on the 16th day. Control animals received tap water and saline instead of ethanol or naloxone, respectively. Both doses of ethanol induced a decrease in spontaneous motility that was antagonized by naloxone. Open-field ambulations were increased by the high dose of ethanol, low-dose lacking effect; naloxone did not modify these ethanol effects. The low dose of ethanol shortened latency time in shuttlebox, the high dose causing escape and freezing responses; none of these effects were modified by naloxone. Therefore, endogenous opioid peptides appear to play a limited role in the chronic effects of ethanol in rats; particularly its effects in tests inducing an increase in the level of anxiety were resistant to naloxone. PMID:9586856

  8. Ethanol-induced impairment of hepatic glycoprotein secretion in the isolated rat liver perfusion model

    SciTech Connect

    Volentine, G.D.; Ogden, K.A.; Tuma, D.J.; Sorrell, M.F.

    1987-05-01

    The authors have previously shown that acute administration of ethanol inhibits hepatic glycoprotein secretion in vivo. This ethanol-induced effect appears to be mediated by its reactive metabolite, acetaldehyde. Since hormonal influences and vascular changes can not be controlled in vivo during ethanol administration, they investigated the effect of ethanol in the isolated perfused liver model. Rat liver from fed animals was perfused with oxygenated KRB at 3 ml/min/g liver for 4 hrs. Since ethanol inhibits proteins synthesis in vitro, protein acceptor pool size was equalized in both ethanol and control perfused livers with 1 mM cycloheximide. /sup 3/H-glucosamine was used to label hepatic secretory glycoproteins in the perfusate. Colchicine, a known inhibitor of protein secretion, impaired the secretion of labeled glycoproteins with a concomitant retention of these export proteins in the liver; therefore, confirming the authors secretory model. Ethanol (50 mM) inhibited the appearance of glucosamine-labeled glycoproteins by 60% into the perfusate as compared to control livers. Pretreatment of animals with cyanamide (an aldehyde dehydrogenase inhibitor) further potentiated this effect of ethanol in the isolated perfused liver. These data suggest that ethanol inhibits hepatic glycoprotein secretion in the isolated liver perfusion model, and this ethanol-induced impairment appears to be mediated by acetaldehyde.

  9. A Low Concentration of Ethanol Impairs Learning but Not Motor and Sensory Behavior in Drosophila Larvae

    PubMed Central

    Ghezzi, Alfredo; Cady, Amanda M.; Najjar, Kristina; Hatch, Michael M.; Shah, Ruchita R.; Bhat, Amar; Hariri, Omar; Haroun, Kareem B.; Young, Melvin C.; Fife, Kathryn; Hooten, Jeff; Tran, Tuan; Goan, Daniel; Desai, Foram; Husain, Farhan; Godinez, Ryan M.; Sun, Jeffrey C.; Corpuz, Jonathan; Moran, Jacxelyn; Zhong, Allen C.; Chen, William Y.; Atkinson, Nigel S.

    2012-01-01

    Drosophila melanogaster has proven to be a useful model system for the genetic analysis of ethanol-associated behaviors. However, past studies have focused on the response of the adult fly to large, and often sedating, doses of ethanol. The pharmacological effects of low and moderate quantities of ethanol have remained understudied. In this study, we tested the acute effects of low doses of ethanol (∼7 mM internal concentration) on Drosophila larvae. While ethanol did not affect locomotion or the response to an odorant, we observed that ethanol impaired associative olfactory learning when the heat shock unconditioned stimulus (US) intensity was low but not when the heat shock US intensity was high. We determined that the reduction in learning at low US intensity was not a result of ethanol anesthesia since ethanol-treated larvae responded to the heat shock in the same manner as untreated animals. Instead, low doses of ethanol likely impair the neuronal plasticity that underlies olfactory associative learning. This impairment in learning was reversible indicating that exposure to low doses of ethanol does not leave any long lasting behavioral or physiological effects. PMID:22624024

  10. Role of neutrophilic elastase in ethanol induced injury to the gastric mucosa

    SciTech Connect

    Kvietys, P.R.; Carter, P.R. )

    1990-02-26

    Intragastric administration of ethanol (at concentrations likely to be encountered by the mucosa during acute intoxication) produces gastritis. Recent studies have implicated neutrophils in the gastric mucosal injury induced by luminal ethanol. The objective of the present study was to assess whether neutrophilic elastase contributes to the ethanol-induced gastric mucosal injury. Sprague-Dawley rats were instrumented for perfusi