Alpha4-containing GABAA receptors in the nucleus accumbens mediate moderate intake of alcohol.

Alcohol has subjective and behavioral effects at the pharmacological levels typically reached during the consumption of one or two alcoholic drinks. Here we provide evidence that an alpha4-subunit-containing GABA(A) receptor contributes to the consumption of low-to-moderate levels of alcohol. Using viral-mediated RNA interference (RNAi), we found that reduced expression of the alpha4 subunit in the nucleus accumbens (NAc) shell of rats decreased their free consumption of and preference for alcohol. The time course for the reduced alcohol intake paralleled the time course of alpha4 mRNA reductions achieved after viral-mediated RNAi for alpha4. Furthermore, the reduction in drinking was region- and alcohol-specific: there was no effect of reductions in alpha4 expression in the NAc core on alcohol intake, and reductions in alpha4 expression in the NAc shell did not alter sucrose or water intake. These results indicate that the GABA(A) receptor alpha4 subunit in the NAc shell mediates alcohol intake.