In contrast, animal studies assert a more direct pathway between alcohol use and α2 subunit-bearing GABAA receptors. Deletion of the α2 subunit via systemic gene knock-out increased the sedative (and ataxic) effects of ethanol in one study [26] but decreased sedation [27] in another, while altering self-administration rates in neither. In contrast, selective silencing of the gene in the central amygdala temporarily ameliorated binge drinking in rodents [28]. The effects of GABRA2 variants on sedation was recently observed in humans, where those carrying a haplotype spanning 5′ GABRG1 to 3′GABRA2 reported decreased sedation upon challenge with alcohol [29].
