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See detailEthanol-induced behaviors in mice genetically deficient in MCH1 receptors
Didone, Vincent ULg; Tirelli, Ezio ULg; Quertemont, Etienne ULg et al

in Alcoholism, Clinical & Experimental Research (2010), 34(8), 93-93

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See detailEffects of histamine H3 receptor modulators on sedative effects induced by ethanol
Didone, Vincent ULg; Quertemont, Etienne ULg

in Alcoholism, Clinical & Experimental Research (2010), 34(8), 93-93

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See detailComparison of the amnesic, ataxic and hypothermic effects of ethanol and acetaldehyde in mice
Closon, Catherine ULg; Quertemont, Etienne ULg

in Alcoholism, Clinical & Experimental Research (2010), 34(8), 92-92

Acetaldehyde, the first metabolite of ethanol, has been suggested to be involved in many behavioral effects of ethanol. However, very few studies have been published on the role of acetaldehyde in the ... [more ▼]

Acetaldehyde, the first metabolite of ethanol, has been suggested to be involved in many behavioral effects of ethanol. However, very few studies have been published on the role of acetaldehyde in the amnesic and ataxic effects of ethanol. The aim of the present studies was to compare the profiles of ethanol and acetaldehyde in several behavioral tests, measuring motor coordination, learning and memory in mice. Female Swiss mice were injected intraperitoneally with ethanol (0-3g/kg) and acetaldehyde (100-300mg/kg). The effects of these substances on a series of representative behaviors were investigated. The amnesic effects were tested with an object recognition task and a one-trial passive avoidance test. Additionally, the rectal temperatures were used to evaluate the hypothermic effects of the two substances. Finally, motor coordination was assessed using the accelerating rotarod test. The results showed that acetaldehyde, like ethanol, altered memory as shown by a reduced performance in the passive avoidance test and the object recognition task. In addition, acetaldehyde at doses between 100 and 300 mg/kg induced significant hypothermic effects, but that was of shorter duration than ethanol-induced hypothermia. Finally, significant ataxic effects of both acetaldehyde and ethanol were observed in the accelerating rotarod test. Overall, the results of the present study clearly show that acetaldehyde, like ethanol, has amnesic, hypothermic and ataxic properties in mice at least at relatively high concentrations. [less ▲]

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See detailResponse inhibition toward alcohol cues in heavy drinkers and alcohol dependent patients
Kreusch, Fanny ULg; Quertemont, Etienne ULg

in Alcoholism, Clinical & Experimental Research (2010), 34(8), 139-139

Alcohol addictive behaviors have been recently associated with a combination of deficits in executive function, such as a weak response inhibition, and potent automatic appetitive responses for alcohol ... [more ▼]

Alcohol addictive behaviors have been recently associated with a combination of deficits in executive function, such as a weak response inhibition, and potent automatic appetitive responses for alcohol-related cues. The aim of the present studies was to investigate response inhibition for alcohol and neutral or soft drink cues in alcohol abusers and alcohol dependent patients. Response inhibition was assessed in a go/nogo task with pictures of alcohols, soft drinks or neutrals objects. In this task, participants had to respond to specific stimuli (go trial) and inhibit that action under a different set of stimuli (nogo trial). Faster responses for alcohol in go trials reflect approach tendency for alcohol cues while false alarm responses for alcohol in nogo trials reflect a deficit in response inhibition toward alcohol-related cues. Moreover, since standard alcohol cues are not equally appreciated across participants, the preference for the different alcoholic drinks presented were measured and analyzed in reference to task responses. Both light and heavy drinkers showed faster responses to alcohol cues in go trial relative to soft/neutral cues. Preliminary results indicate a negative relationship between the preference scores for alcohols and the reaction times to those stimuli in go trials. The present study also demonstrated that the presence of brands logo significantly altered the discrimination and reactions time patterns of response to alcohol and soft cues. [less ▲]

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See detailGradual changes in the sensitivity to the stimulant and sedative effects of ethanol during adolescence in Swiss mice
Quoilin, Caroline ULg; Didone, Vincent ULg; Quertemont, Etienne ULg

in Alcoholism, Clinical & Experimental Research (2010), 34(8), 97-97

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See detailAcetaldehyde and the hypothermic effects of ethanol in mice.
Closon, Catherine ULg; Didone, Vincent ULg; Tirelli, Ezio ULg et al

in Alcoholism, Clinical & Experimental Research (2009), 33(11), 2005-14

BACKGROUND: Acetaldehyde, the first metabolite of ethanol, has been suggested to be involved in many behavioral effects of ethanol. However, few studies have investigated the hypothermic effects of ... [more ▼]

BACKGROUND: Acetaldehyde, the first metabolite of ethanol, has been suggested to be involved in many behavioral effects of ethanol. However, few studies have investigated the hypothermic effects of acetaldehyde or the contribution of acetaldehyde to ethanol-induced hypothermia. The aim of the present study is to better understand the hypothermic effects of acetaldehyde and the possible contribution of acetaldehyde in ethanol-induced hypothermia, especially under conditions leading to acetaldehyde accumulation. METHODS: Female Swiss mice were injected intraperitoneally with ethanol and acetaldehyde and their rectal temperatures were measured with a digital thermometer at various time points after the injections. Experiment 1 compared the hypothermic effects of various acetaldehyde doses (0 to 300 mg/kg) with a reference dose of ethanol (3 g/kg). Experiment 2 tested the effects of a pretreatment with the aldehyde dehydrogenase (ALDH) inhibitor cyanamide (25 mg/kg) on ethanol- and acetaldehyde-induced hypothermia. In experiments 3 and 4, mice received a combined pretreatment with cyanamide and the alcohol dehydrogenase (ADH) inhibitor 4-Methylpyrazole (10 mg/kg) before the injection of ethanol or acetaldehyde. RESULTS: Acetaldehyde at doses between 100 and 300 mg/kg induced significant hypothermic effects, but of shorter duration than ethanol-induced hypothermia. The inhibition of ALDH enzymes by cyanamide induced a strong potentiation of both ethanol- and acetaldehyde-induced hypothermia. The pretreatment with 4-MP prevented the potentiation of ethanol-induced hypothermia by cyanamide, but slightly increased the potentiation of acetaldehyde-induced hypothermia by cyanamide. CONCLUSIONS: The results of the present study clearly show that acetaldehyde has hypothermic properties in mice at least at relatively high concentrations. Furthermore, the accumulation of acetaldehyde following ALDH inhibition strongly enhanced the hypothermic effects of ethanol. These latter results confirm the hypothermic properties of acetaldehyde and show that acetate, the next step in ethanol metabolism, is not involved in these hypothermic effects. Finally, the experiment with 4-MP indicates that the potentiating effects of cyanamide are mediated by the peripheral accumulation of acetaldehyde, which then reaches the brain to induce a severe hypothermia. [less ▲]

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See detailBehavioral effects of acetaldehyde in mice and rats: From reinforcement to amnesia
Quertemont, Etienne ULg; Didone, Vincent ULg; Closon, Catherine ULg

in Alcoholism, Clinical & Experimental Research (2008), 32(6), 289-289

Whereas human studies keep reporting evidence that acetaldehyde accumulation prevents alcohol drinking and alcoholism, animal studies support a rewarding rather than aversive role for acetaldehyde. In ... [more ▼]

Whereas human studies keep reporting evidence that acetaldehyde accumulation prevents alcohol drinking and alcoholism, animal studies support a rewarding rather than aversive role for acetaldehyde. In recent years, the reinforcing properties of acetaldehyde were demonstrated in various rodent strains and using different experimental methods. These results led to the hypothesis that acetaldehyde might be involved in the addictive properties of alcohol. In addition to its possible role in the reinforcing properties of alcohol, there is also evidence that acetaldehyde is involved in many other behavioral effects of ethanol. Using various behavioral procedures with both mice and rats, we have studied the behavioral effects of direct acetaldehyde injections. Additionally, in independent experiments we have compared the effects of ethanol in mice with or without a pre-treatment with the aldehyde dehydrogenase inhibitor cyanamide, which produces acetaldehyde accumulation. The results of these studies show that acetaldehyde produces a wide spectrum of behavioral effects, including reinforcement, aversion, sedation, ataxia and amnesia. These effects were mainly dependent upon acetaldehyde doses, with some of them showing an inverted U shape dose-response curve. These results also suggest that acetaldehyde might mediate or contribute to many of the behavioral effects of ethanol and especially to alcohol abuse and alcoholism. [less ▲]

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See detailGender and age at drinking onset affect voluntary alcohol consumption but neither the alcohol deprivation effect nor the response to stress in mice.
Tambour, Sophie ULg; Brown, Lauren L; Crabbe, John C

in Alcoholism, Clinical & Experimental Research (2008), 32(12), 2100-6

BACKGROUND: Epidemiological studies suggest that initiation of alcohol drinking at an early age is associated with an increased risk of developing an alcohol use disorder later in life. Nevertheless ... [more ▼]

BACKGROUND: Epidemiological studies suggest that initiation of alcohol drinking at an early age is associated with an increased risk of developing an alcohol use disorder later in life. Nevertheless, relatively few studies using animal models have investigated the relationship between age of onset of drinking and ethanol drinking patterns in adulthood. Besides age at drinking onset, other factors such as gender could also affect the pattern of development of alcohol consumption. In rodents, many studies have shown that females drink more than males. However, even if it is assumed that hormonal changes occurring at puberty could explain these differences, only one study performed in rats has investigated the emergence of sex-specific alcohol drinking patterns in adolescence and the transition from adolescence to adulthood. The aim of the present study was to compare the acquisition of voluntary alcohol consumption, relapse-like drinking (the Alcohol Deprivation Effect-ADE) and stress-induced alcohol drinking in male and female outbred mice that acquired alcohol consumption during adolescence or adulthood. METHODS: Separate groups of naive female and male WSC-1 mice aged +/- 28 days (adolescents) or +/-70 days (adults) were given ad libitum access to water and 6% ethanol solution for 8 weeks (1st to 8th week) before undergoing a 2-week deprivation phase (9th and 10th week). After the deprivation period, 2-bottle preference testing (ethanol vs. water) resumed for 3 weeks (11th to 13th). During the 13th week, all animals were subjected to restraint stress for 2 consecutive days. RESULTS: Over the entire time course of the experiment, ethanol intake and preference increased in females (both adults and adolescents). Adolescent animals (both females and males) showed a transient increase in alcohol consumption and preference compared to adults. However, by the end of continuous alcohol exposure (when all mice were adults), ethanol intake was not affected by age at drinking onset. A deprivation phase was followed by a rise in ethanol intake (ADE) that was not affected by sex or age. Finally, stress did not alter alcohol self-administration either during or after its occurrence. CONCLUSIONS: Emergence of greater alcohol consumption in adult females does not seem to be limited to a specific developmental period (i.e., puberty). Age of voluntary drinking onset (adolescence vs. adulthood) does not affect eventual alcohol intake in adult WSC-1 mice and does not modify the transient increase in ethanol consumption after alcohol deprivation. [less ▲]

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See detailAlcohol drinking in MCH receptor-1-deficient mice
Duncan, E. A.; Sorrell, J. E.; Adamantidis, Antoine ULg et al

in Alcoholism, Clinical & Experimental Research (2007), 31(8), 1325-1337

Background: Recently, we demonstrated that exogenous melanin-concentrating hormone (MCH) increases alcohol drinking in rats when administered into the brain. However, because the physiological relevance ... [more ▼]

Background: Recently, we demonstrated that exogenous melanin-concentrating hormone (MCH) increases alcohol drinking in rats when administered into the brain. However, because the physiological relevance of this finding is unclear, we tested the hypothesis that endogenous MCH signaling enhances alcohol consumption. Methods: Alcohol intake was assessed in male and female wildtype (WT), heterozygous (HET), and homozygous MCH receptor-1-deficient (KO) mice. Mice were given 24-hour access to a series of alcohol-containing solutions. Following this, the mice were given limited (1-hour) access to 10% alcohol. Finally, mice were allowed 24-hour access to sucrose/quinine as a caloric control and a means to assess taste preference. A naive cohort of male WT and KO mice was tested for alcohol clearance following intraperitoneal administration of 3 g/kg alcohol. Another naive cohort of female mice was utilized to confirm that intracerebroventricular administration of MCH (5 mu g) would augment alcohol drinking in mice. Results: Exogenous MCH enhanced 10% alcohol consumption in mice (saline=0.45 +/- 0.08 g/kg, 5 mu g MCH=0.94 +/- 0.20 g/kg). Male KO mice consumed more 10% alcohol (11.50 +/- 1.31 g/kg) than WT (6.26 +/- 1.23 g/kg) and HET mice (6.49 +/- 1.23 g/kg) during ad libitum access. However, alcohol intake was similar among genotypes during 1 hour daily access. Male KO mice tended to consume less 17.75% sucrose+1.3 mM quinine than controls (WT=10.5 +/- 3.6, HET=7.5 +/- 1.7, KO=4.4 +/- 0.9 g/kg). Alcohol metabolism was similar between WT and KO mice. Conclusions: The finding that male KO consume more alcohol than WT and HET mice, are reminiscent of the counterintuitive reports that KO mice are hyperphagic and yet eat more when administered exogenous MCH. Changes in taste preference or alcohol metabolism do not appear to be important for the increased alcohol drinking in KO mice. [less ▲]

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See detailTime Course of Attention for Alcohol Cues in Abstinent Alcoholic Patients: The Role of Initial Orienting
Noel, Xavier; Colmant, Maud; Van der Linden, Martial ULg et al

in Alcoholism, Clinical & Experimental Research (2006), 30(11), 1871-1877

Objective: Addicted people are characterized by enhanced attention for drug cues leading to drug use. However, there is little research on the component processes of attention in individuals with ... [more ▼]

Objective: Addicted people are characterized by enhanced attention for drug cues leading to drug use. However, there is little research on the component processes of attention in individuals with alcoholism. Here, we examine 2 distinct components of attention in abstinent alcohol-dependent individuals and social drinkers of alcohol, that is to say, the initial orienting to alcohol-related cues, and the maintenance of attention to them. Method: The present study used an ‘‘alcohol’’ version of the visual probe detection task with alcohol-related or neutral pictures being presented briefly (i.e., 50 ms), to assess initial orienting, or longer (i.e., 500 and 1,250 ms), to assess the maintenance of attention. Results: Only alcoholic patients were faster in detecting a probe displayed immediately after pictures related to alcohol presented for 50 ms than in detecting the same probe replacing non– alcohol-related pictures. However, when pictures were presented for 500 ms, only social alcohol drinkers were faster in detecting the probe replacing alcohol scenes. At a stimulus of 1,250 ms duration, no group showed attentional bias toward alcohol cues. In addition, the severity of alcoholism measured by the total number of prior detoxification treatments was positively correlated with the attentional bias (or ‘‘attraction’’) for alcohol pictures presented for 50 ms. Conclusions: These results show that, subsequent to initial visual orienting to alcohol-related cues, abstinent patients’ attention was disengaged from these stimuli, thus suggesting a visual approachdisengagement attentional pattern. The influence of these findings on relapse was discussed. [less ▲]

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See detailIs ethanol a pro-drug? Acetaldehyde contribution to brain ethanol effects
Quertemont, Etienne ULg; Eriksson, Peter C. J.; Zimatkin, Sergey M. et al

in Alcoholism, Clinical & Experimental Research (2005), 29(8), 1514-1521

This article presents the proceedings of a symposium at the 2004 meeting of the International Society for Biomedical Research on Alcoholism, held in Mannheim, Germany. The symposium was organized by ... [more ▼]

This article presents the proceedings of a symposium at the 2004 meeting of the International Society for Biomedical Research on Alcoholism, held in Mannheim, Germany. The symposium was organized by Etienne Quertemont and chaired by C. J. Peter Eriksson. The presentations were (1) Brain ethanol metabolism and its behavior consequences, by Sergey M. Zimatkin and P. S. Pronko; (2) Acetaldehyde increases dopaminergic neuronal activity: a possible mechanism for acetaldehyde reinforcing effects, by Marco Diana and Milena Pisano; (3) Contrasting the reinforcing actions of acetaldehyde and ethanol within the ventral tegmental area (VTA) of alcohol-preferring (P) rats, by Zachary A. Rodd and Richard R. Bell; (4) Molecular and biochemical changes associated with acetaldehyde toxicity, by Roberta J. Ward; and (5) Role of acetaldehyde in human alcoholism and alcohol abuse, by C. J. Peter Eriksson [less ▲]

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See detailThe role of acetaldehyde in the central effects of ethanol
Quertemont, Etienne ULg; Grant, Kathleen A.; Correa, Merce et al

in Alcoholism, Clinical & Experimental Research (2005), 29(2), 221-234

This article represents the proceedings of a symposium at the 2004 annual meeting of the Research Society on Alcoholism in Vancouver, Canada. The symposium was organized by Etienne Quertemont and chaired ... [more ▼]

This article represents the proceedings of a symposium at the 2004 annual meeting of the Research Society on Alcoholism in Vancouver, Canada. The symposium was organized by Etienne Quertemont and chaired by Kathleen A. Grant. The presentations were (1) Behavioral stimulant effects of intracranial injections of ethanol and acetaldehyde in rats, by Merc Correa, Maria N. Arizzi and John D. Salamone; (2) Behavioral characterization of acetaldehyde in mice, by Etienne Quertemont and Sophie Tambour; (3) Role of brain catalase and central formed acetaldehyde in ethanol's behavioral effects, by Carlos M.G. Aragon; (4) Contrasting the reinforcing actions of acetaldehyde and ethanol within the ventral tegmental area (VTA) of alcohol-preferring (P) rats, by William J. McBride, Zachary A. Rodd, Avram Goldstein, Alejandro Zaffaroni and Ting-Kai Li; and (5) Acetaldehyde increases dopaminergic transmission in the limbic system, by Milena Pisano and Marco Diana. [less ▲]

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See detailBehavioral characterization of acetaldehyde in mice
Quertemont, Etienne ULg; Tambour, Sophie ULg; Tirelli, Ezio ULg

in Alcoholism, Clinical & Experimental Research (2004), 28(5), 196-196

Acetaldehyde, the first product of ethanol metabolism, has long been speculated to be involved in many of the behavioral effects of ethanol, although its precise role remains a matter of debate. However ... [more ▼]

Acetaldehyde, the first product of ethanol metabolism, has long been speculated to be involved in many of the behavioral effects of ethanol, although its precise role remains a matter of debate. However, most of the results supporting a role for acetaldehyde in ethanol’s effects come from studies in which ethanol metabolism was pharmacologically manipulated, whereas the behavioral properties of acetaldehyde itself are still largely unknown. In the present studies, we have characterized the locomotor, hypnotic, anxiolytic and amnesic effects of both ethanol and acetaldehyde in C57BL/6J and CD1 mice. Several classical behavioral tests were used: the open field, the loss of righting reflex, the plus-maze, the place conditioning and the passive avoidance. The results show that acetaldehyde similarly to ethanol induces sedation and hypnotic effects at high doses. In addition, acetaldehyde displays potent amnesic effects in the passive avoidance test, suggesting that the first metabolite of ethanol might be critically involved in the memory-impairing effects of ethanol. However, in contrast to ethanol, acetaldehyde does not show anxiolytic properties in the plus-maze. In a second part of the present studies, acetaldehyde contribution to ethanol’s behavioral effects was investigated by using several inhibitors of ethanol metabolism (3-amino-1,2,4-triazole, a catalase inhibitor, and disulfiram, an aldehyde dehydrogenase inhibitor). Overall, the present results suggest that acetaldehyde is involved in some of ethanol’s behavioral effects (amnesia, locomotor depression, sedation) but not in others (in particular anxiolysis). [less ▲]

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See detailRole of acetaldehyde in the discriminative stimulus effects of ethanol
Quertemont, Etienne ULg; Grant, Kathleen A

in Alcoholism, Clinical & Experimental Research (2002), 26(6), 812-817

Background: Acetaldehyde has been suggested to mediate some of the effects of ethanol. Acetaldehyde can be produced by the enzyme catalase within the brain after ethanol administration. The catalase ... [more ▼]

Background: Acetaldehyde has been suggested to mediate some of the effects of ethanol. Acetaldehyde can be produced by the enzyme catalase within the brain after ethanol administration. The catalase inhibitor 3-amino-1,2,4-triazole (AT) reduces the production of acetaldehyde, and AT administration can reduce a number of ethanol-induced behavioral effects; this suggests the involvement of acetaldehyde in these behaviors. However, a role for acetaldehyde in mediating the discriminative stimulus effects of ethanol remains unclear. Methods: The contribution of acetaldehyde to the discriminative stimulus effects of ethanol was investigated by use of a two-lever drug discrimination paradigm with food reinforcement. Male Long-Evans rats were trained to discriminate water from either 1.0 or 2.0 g/kg ethanol. Stimulus substitution tests were conducted with ethanol (0 –2.5 g/kg by gavage) and acetaldehyde (0–300 mg/kg intraperitoneally). A cumulative dose-response procedure was then used to investigate the effects of pretreatments with AT (0.5 and 1.0 g/kg intraperitoneally) on ethanol discrimination. Results: Acetaldehyde up to doses that decreased response rates (300 mg/kg) did not substitute for the discriminative stimulus effects of 1.0 or 2.0 g/kg ethanol. In addition, AT pretreatment did not affect the dose-response curves for ethanol discrimination. Conclusions: These results show that exogenous acetaldehyde administration does not produce discriminative stimulus effects that are similar to those of ethanol. Also, pretreatment with the catalase inhibitor did not affect the dose-response curve for ethanol discrimination, and this suggests that endogenously produced acetaldehyde does not contribute to the discriminative stimulus effects of ethanol. Together these results suggest that acetaldehyde does not mediate the discriminative stimulus effects of 1.0 to 2.0 g/kg ethanol. [less ▲]

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See detailTime-course of brain ethanol levels and the acoustic startle response in the rat following the acute administration of ethanol
Williams, S. A.; Quertemont, Etienne ULg; Green, Heather et al

in Alcoholism, Clinical & Experimental Research (2001), 25

It is known that ethanol administration inhibits the acoustic startle response, but whether this sensitivity varies within-session has not been investigated. The purpose of the present study was to ... [more ▼]

It is known that ethanol administration inhibits the acoustic startle response, but whether this sensitivity varies within-session has not been investigated. The purpose of the present study was to compare the time-course of ethanol levels in brain with alterations in the acoustic startle response. Three experiments were conducted in adult male Sprague-Dawley rats. 1) Ethanol concentrations in brain were determined by microdialysis following the acute administration of 0.3, 1.0 and 3.0 g/kg ig of ethanol. 2) The effect of ethanol on the acoustic startle response was determined after the same doses. 3) The acoustic startle response was determined during two time periods, at 2-18 and 30-46 minutes, after ethanol administration to evaluate periods of ascending and descending ethanol levels. In expt. 1, brain levels of ethanol rose rapidly, peaking within 4-8 minutes following all doses. In expt. 2, ethanol administration reduced the acoustic startle response in a dose-related manner; all doses significantly reduced the response. In expt. 3, prepulse inhibition was diminished by ethanol during a very short period immediately after ethanol administration, whereas the acoustic startle response was inhibited only during later times. These data indicate that the acoustic startle response was exquisitely sensitive to ethanol, even at doses as low as 0.3 g/kg. In addition, prepulse inhibition was selectively disrupted immediately after ethanol administration, which suggests that this phenomenon may accompany the short-lived ascending limb of the brain ethanol curve. Supported by AA 12356 (DL) and AA11997. [less ▲]

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See detailAlcoholic's deficit in the decoding of emotional facial expression
Philippot, P; Kornreich, C; Blairy, Sylvie ULg et al

in Alcoholism, Clinical & Experimental Research (1999), 23(6), 1031-1038

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See detailTaurine - a modulator of ethanol toxicity. From basic concepts to clinical reality
Dahchour, Abdelkhader; Lallemand, Frédéric; Quertemont, Etienne ULg et al

in Alcoholism, Clinical & Experimental Research (1998), 22

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See detailNeurotoxic effects of acetaldehyde
Ward, Roberta J.; Lallemand, Frédéric; Dahchour, Abdelkhader et al

in Alcoholism, Clinical & Experimental Research (1998), 22

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See detailThe role of taurine in ethanol reinforcing effects
Quertemont, Etienne ULg; de Bethune, Coraline; De Witte, Philippe

in Alcoholism, Clinical & Experimental Research (1998), 22

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See detailAcetaldehyde but not ethanol induces conditioned stimulus preference
Quertemont, Etienne ULg; De Witte, Philippe

in Alcoholism, Clinical & Experimental Research (1998), 22

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