The genetics of alcoholism and alcohol abuse

Enoch, Mary‐Anne; Goldman, David

doi:10.1007/s11920-001-0012-3

Cited by 152 publications

(120 citation statements)

References 75 publications

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“…85000 deaths/ year in the US alone, making it the number three externally modifiable cause of mortality (Mokdad et al, 2004). Genetic susceptibility factors interact with the environment to account for a considerable heritability in alcohol use disorders (Enoch and Goldman, 2001). Identification of heritable susceptibility factors offers a promise of improved and ultimately individualized pharmacological treatment in this disorder, a promise which is in part beginning to be realized (Oslin et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

Hansson

Bermúdez‐Silva²,

Malinen

et al. 2006

Neuropsychopharmacol

151

155

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Endocannabinoid signaling has recently been implicated in ethanol-seeking behavior. We analyzed the expression of endocannabinoidrelated genes in key brain regions of reward and dependence, and compared them between the alcohol-preferring AA (Alko Alcohol) and nonpreferring ANA (Alko Non-Alcohol) rat lines. A decreased expression of fatty acid amidohydrolase (FAAH), the main endocannabinoid-degrading enzyme, was found in prefrontal cortex (PFC) of AA rats, and was accompanied by decreased enzyme activity in this region. Binding of the endocannabinoid-cannabinoid 1 (CB1) receptor ligand 3 [H]SR141716A, and [35S]GTPgS incorporation stimulated by the CB1 agonist WIN 55,212-2 were downregulated in the same area. Together, this suggests an overactive endocannabinoid transmission in the PFC of AA animals, and a compensatory downregulation of CB1 signaling. The functional role of impaired FAAH function for alcohol self-administration was validated in two independent ways. The CB1 antagonist SR141716A potently and dose-dependently suppressed self-administration in AA rats when given systemically, or locally into the PFC, but not in the striatum. Conversely, intra-PFC injections of the competitive FAAH inhibitor URB597 increased ethanol self-administration in nonselected Wistar rats. These results show for the first time that impaired FAAH function may confer a phenotype of high voluntary alcohol intake, and point to a FAAH both as a potential susceptibility factor and a therapeutic target.

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Section: Introductionmentioning

confidence: 99%

Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

Hansson

Bermúdez‐Silva²,

Malinen

et al. 2006

Neuropsychopharmacol

151

155

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“…Twin studies have shown substantial genetic influences (Ͼ50%) on both alcohol and nicotine addiction (Carmelli et al, 1992;Enoch and Goldman, 2001). Twin studies have also indicated that genetic factors may account for the co-abuse of nicotine and alcohol (Swan et al, 1997;Bierut et al, 2004;Goldman et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Increased Vulnerability to Nicotine Self-Administration and Relapse in Alcohol-Naive Offspring of Rats Selectively Bred for High Alcohol Intake

et al. 2006

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The prevalence of smoking in human alcoholics is substantially higher than in the general population, and results from twin studies suggest that a shared genetic vulnerability underlies alcohol and nicotine addiction. Here, we directly tested this hypothesis by examining nicotine-taking behavior in alcohol-naive offspring of alcohol-preferring (P) rats and alcohol-nonpreferring (NP) rats that had been selectively bred for high and low alcohol intake. The self-administration of intravenous nicotine (0.015-0.060 mg/kg per infusion) in P rats was more than twice than that of NP rats. Nicotine seeking induced by reexposure to nicotine cues in extinction tests was also substantially greater in P rats than in NP rats. In a subsequent relapse test, priming nicotine injections reinstated drug seeking in P rats but not NP rats. P rats also self-administered higher amounts of oral sucrose (1-20%) than NP rats, a finding consistent with previous reports. In contrast, self-administration of intravenous cocaine (0.1875-1.125 mg/kg per infusion) was remarkably similar in the P and NP rats; however, P-NP differences in cocaine seeking emerged in subsequent extinction and cocaine priming-induced reinstatement tests. In both cases, lever responding was higher in P rats than in NP rats. Thus, alcohol-naive offspring of rats genetically selected for high alcohol intake are highly susceptible to nicotine self-administration and relapse, and this susceptibility is not likely caused by general reward deficits in NP rats. The present findings provide experimental evidence for the hypothesis that a shared genetic determinant accounts for the co-abuse of nicotine and alcohol.

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“…As with other drugs of abuse, the development of alcohol abuse and dependence are influenced by a number of biological factors, including genetics. Human epidemiological research consistently reveals significant heritability of alcohol abuse and alcoholism [11], and recent advances in molecular biology have enabled the search for molecular genetic risk factors in humans and in non-human primate models [1,2,30]. In addition to these correlational approaches, laboratory researchers also utilize a variety of experimental methodologies to better understand genetic contributions to addiction.…”

Section: Introductionmentioning

confidence: 99%

Dissociation between the aversive and pharmacokinetic effects of ethanol in female Fischer and Lewis rats

Roma¹,

Chen²,

Barr³

et al. 2007

Behavioural Brain Research

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In humans and laboratory animal models, vulnerability to alcohol abuse is influenced by endogenous factors such as genotype. Using the inbred Fischer and Lewis rat strains, we previously reported stronger conditioned taste aversions (CTA) in male Fischer rats that could not be predicted by genotypic differences in alcohol absorption [34]. The present study made similar assessments in Fischer and Lewis females via four-trial CTA induced by 1 or 1.5 g/kg intraperitoneal (IP) ethanol (n = 10-12/strain/dose) as well as measures of blood alcohol concentrations (BAC) at 15, 60 and 180 min post-injection with 1.5 g/kg IP ethanol or saline (n = 7-8/strain/dose). Dose-dependent CTAs were produced, but the strains did not differ from each other in these measures; however, BACs in the Lewis females were significantly higher than Fischer at all three time points. As with males of the Fischer and Lewis genotypes, a dissociation between BACs and the aversive effects of alcohol was observed. These data are the first assessments of these particular phenotypes in Fischer and Lewis females, and when considered with the historical data, suggest a Genotype × Sex interaction in the centrally-mediated sensitivity to alcohol's aversive effects.

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The genetics of alcoholism and alcohol abuse

Cited by 152 publications

References 75 publications

Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

Increased Vulnerability to Nicotine Self-Administration and Relapse in Alcohol-Naive Offspring of Rats Selectively Bred for High Alcohol Intake

Dissociation between the aversive and pharmacokinetic effects of ethanol in female Fischer and Lewis rats

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