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The Journal of Neuroscience, January 14, 2009, 29(2):543-549; doi:10.1523/JNEUROSCI.3199-08.2009

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Behavioral/Systems/Cognitive
{alpha}4-Containing GABAA Receptors in the Nucleus Accumbens Mediate Moderate Intake of Alcohol

Mridula Rewal,1 Rachel Jurd,1 T. Michael Gill,1 Dao-Yao He,1 Dorit Ron,1,2,3,4 and Patricia H. Janak1,2,3,4

1Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608, and 2Program in Neuroscience, 3Department of Neurology, and 4Wheeler Center for the Neurobiology of Addiction, University of California, San Francisco, San Francisco, California 94143

Correspondence should be addressed to Patricia H. Janak, Ernest Gallo Clinic and Research Center, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608. Email: pjanak{at}gallo.ucsf.edu

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 {alpha}4-subunit-containing GABAA 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 {alpha}4 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 {alpha}4 mRNA reductions achieved after viral-mediated RNAi for {alpha}4. Furthermore, the reduction in drinking was region- and alcohol-specific: there was no effect of reductions in {alpha}4 expression in the NAc core on alcohol intake, and reductions in {alpha}4 expression in the NAc shell did not alter sucrose or water intake. These results indicate that the GABAA receptor {alpha}4 subunit in the NAc shell mediates alcohol intake.

Key words: ethanol; addiction; extrasynaptic; self-administration; tonic current; RNA interference

Received July 9, 2008; revised Nov. 13, 2008; accepted Dec. 10, 2008.

Correspondence should be addressed to Patricia H. Janak, Ernest Gallo Clinic and Research Center, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608. Email: pjanak{at}gallo.ucsf.edu






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