ALCOHOL CHALLENGE

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alcohol abuse and dependence are important public health problems. Inherited (i.e., genetic) risk factors are thought to be important in the development of alcohol use disorders. Recent family-based and case-control studies of genetic factors in alcohol dependence indicate that variation in the GABA-A gene, GABRA2, is associated with alcohol dependence. Our preliminary results from alcohol challenge studies in humans suggest that variation in GABRA2 also influences the subjective effects of alcohol, suggesting a potential mechanism by which the gene may influence risk of alcohol dependence. Based on these preliminary data, the aims of this study are to: 1) examine the effect of alcohol on multiple domains of the response to acute alcohol administration in 30 social drinkers and to 2) examine the moderating effect of GABRA2 genotype on these subjective measures in response to acute alcohol administration. We hypothesize that, during the ascending limb of the BrAC, the stimulating and rewarding effects of alcohol will be moderated by GABRA2 genotype, such that individuals who are homozygous for the A-allele at SNP rs279858 (an intronic marker in GABRA2) will show a greater response to the effects of alcohol than will carriers of the alcohol-dependence-associated G-allele. In contrast, other effects of alcohol, such as sedation, motor incoordination, and decreased cognitive performance (the latter two measured by static ataxia and working memory, respectively), will not be influenced by GABRA2 genotype, as these effects are more likely to involve modulation of receptors containing the GABA-A ¿-1 subunit. The identification of specific genetic determinants for variation in the quality or magnitude of responses to alcohol may help in our understanding of why some individuals are vulnerable to, or protected from, alcohol dependence.