Sensitivity to the acute effects of ethanol has also been linked to the GABRA2 gene (Haughey et al. 2008; Pierucci-Lagha et al. 2005). Interestingly, individuals homozygous for the A-allele at GABRA2 reported greater stimulant, sedative, and gastrointestinal subjective effects of acute ethanol, compared with subjects with one or more G-alleles (the G-allele is overrepresented among ethanol-dependent subjects; Covault et al. 2004). Administration of the neuroactive steroid biosynthesis inhibitor finasteride antagonized some of the behavioral effects of ethanol particularly among individuals homozygous for the A-allele, suggesting that neuroactive steroids may be mediating the subjective effects of ethanol, like in rodent studies (Pierucci-Lagha et al. 2005). The genetic association of ethanol dependence with GABRA2 is of significant functional interest as animal studies have identified the α2 subunit as the primary α subunit in limbic regions (McKernan and Whiting 1996). The α2 subunit mediates the anxiolytic effect of benzodiazepines and barbiturates (Dixon et al. 2008; Rudolph et al. 1999) as well as the sedative-hypnotic, but not the sedative, effects of combined exposure to ethanol and benzodiazepines in genetically modified mouse studies (Tauber et al. 2003).
