We recently sought to investigate the contribution of the α4βδ GABAARs to ethanol’s behavioral effects. We used viral-mediated RNA interference (RNAi), which allows for region-specific reductions of target gene mRNA levels in adult animals (Hommel et al. 2003; Lasek et al. 2007; Jeanblanc et al. 2009), to selectively down-regulate the expression of the α4 GABAAR subunit in the shell region of the nucleus accumbens (NAc) of rats. We found that ethanol self-administration in the two-bottle preference test was reduced after NAc shell knockdown of the α4 GABAAR subunit, but intake of sucrose was unaffected (Rewal et al. 2009). These findings indicate that α4-containing GABAARs, in a region long considered to mediate processes of reward and reinforcement (Koob, Sanna & Bloom 1998; McBride, Murphy & Ikemoto 1999; Everitt & Robbins 2005), contribute to ethanol intake. Interestingly, a previous study found that mice with a global deletion of the gene encoding the δ GABAAR subunit drink less ethanol than wild-type mice (Mihalek et al. 2001), suggesting a role for δ subunit-containing GABAARs in ethanol intake. Taken together, these findings provide strong evidence that the α4βδ GABAAR contributes to mechanisms underlying ethanol intake.
