title: Alpha4-containing GABAA receptors in the nucleus accumbens mediate moderate intake of alcohol.
abstract: 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.
authors.affiliation: Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608, USA.
authors.forename: Mridula
authors.initials: M
authors.lastname: Rewal
authors.forename: Rachel
authors.initials: R
authors.lastname: Jurd
authors.forename: T Michael
authors.initials: TM
authors.lastname: Gill
authors.forename: Dao-Yao
authors.initials: DY
authors.lastname: He
authors.forename: Dorit
authors.initials: D
authors.lastname: Ron
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Janak
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D002461:Cell Line, Transformed; D002849:Chromatography, Gas / Q000379:methods; D003216:Conditioning, Operant / Q000502:physiology; D004435:Eating / Q000235:genetics / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection / Q000379:methods
chemical_list: C546260:GABRA4 protein, human; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011963:Receptors, GABA-A; D049452:Green Fluorescent Proteins; D000431:Ethanol