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Study Shows that a Specific GABA(A) Receptor Plays a Critical Role in Alcohol Intake
Recent research suggests that receptors for the neurotransmitter GABA(A) that lie outside of the synapse and which contain a molecular fragment known as a delta-subunit are sensitive to alcohol, raising the possibility that these receptors might help produce alcohol’s reinforcing effects after consuming one or a few drinks. In the current study, researchers tested the hypothesis that these extrasynaptic GABA(A) receptors in an area of the brain’s reward circuitry called the nucleus accumbens (NAc) are necessary for oral alcohol consumption. They used genetic-engineering technology to reduce expression of the GABA(A) receptor delta-subunit in adult rats in different parts of the NAc, a structure that consists of a core and a shell, which is subdivided into ventral, medial, and dorsal parts. They found that by inhibiting the delta-subunit in the medial shell region of the NAc, but not in the ventral or lateral shell or in the core, reduced the rats’ alcohol intake. In contrast, delta-subunit inhibition in the medial shell did not affect intake of a 2% sucrose solution, suggesting that the effects of GABA(A) receptor delta-subunit reduction are specific to alcohol. The findings provide strong evidence that extrasynaptic delta-subunit-containing GABA(A) receptors in the medial shell of the NAc are critical for the reinforcing effects of oral ethanol.