Extrasynaptic delta-containing GABAA receptors in the nucleus accumbens dorsomedial shell contribute to alcohol intake.

Recent findings suggest that extrasynaptic δ-subunit-containing GABA(A) receptors are sensitive to low-to-moderate concentrations of alcohol, raising the possibility that these receptors mediate the reinforcing effects of alcohol after consumption of one or a few drinks. We used the technique of viral-mediated RNAi to reduce expression of the GABA(A) receptor δ-subunit in adult rats in localized regions of the nucleus accumbens (NAc) to test the hypothesis that δ-subunit-containing GABA(A) receptors in the NAc are necessary for oral alcohol consumption. We found that knockdown of the δ-subunit in the medial shell region of the NAc, but not in the ventral or lateral shell or in the core, reduced alcohol intake. In contrast, δ-subunit knockdown in the medial shell did not affect intake of a 2% sucrose solution, suggesting that the effects of GABA(A) receptor δ-subunit reduction are specific to alcohol. These results provide strong evidence that extrasynaptic δ-subunit-containing GABA(A) receptors in the medial shell of the NAc are critical for the reinforcing effects of oral ethanol.