title: Alpha4 subunit-containing GABAA receptors in the accumbens shell contribute to the reinforcing effects of alcohol.
abstract: The α4βδ gamma-aminobutyric acid A receptor (GABA(A) R) has been proposed to mediate the rewarding effects of low-to-moderate concentrations of alcohol (ethanol) that approximate those achieved by social drinking. If this is true, then this receptor should be necessary for the reinforcing effects of ethanol as assessed in an instrumental self-administration procedure in which rats are trained to lever press for oral ethanol. We used viral-mediated RNA interference to transiently reduce expression of the α4 GABA(A) R subunit in the shell region of the nucleus accumbens (NAc). We found that responding for ethanol was significantly reduced after α4 reductions in the NAc shell, but not NAc core. This reduction was specific to ethanol, as responding for sucrose was not altered. The presence of ethanol was also required as unreinforced responding for ethanol in subjects previously trained to respond for ethanol (i.e. responding during an extinction test) was not altered. In addition, responding during reinforced sessions was not altered during the initial 5 minutes of the session, but decreased after 5 minutes, following multiple reinforced responses. Together, these findings indicate that the α4 GABA(A) R subunit in the NAc shell is necessary for the instrumental reinforcing effects of oral ethanol, further supporting a role for α4-containing GABA(A) Rs in the rewarding/reinforcing effects of ethanol. Possible pharmacological and non-pharmacological explanations for these effects are considered.
authors.affiliation: Ernest Gallo Clinic and Research Center, University of California at San Francisco, 5858 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Mridula
authors.initials: M
authors.lastname: Rewal
authors.forename: Rachel
authors.initials: R
authors.lastname: Donahue
authors.forename: T Michael
authors.initials: TM
authors.lastname: Gill
authors.forename: Hong
authors.initials: H
authors.lastname: Nie
authors.forename: Dorit
authors.initials: D
authors.lastname: Ron
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Janak
mesh_terms: D000256:Adenoviridae; D000428:Alcohol Drinking / Q000523:psychology; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000502:physiology*; D012054:Reinforcement, Psychology; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage
chemical_list: D034741:RNA, Small Interfering; D011963:Receptors, GABA-A; D013549:Sweetening Agents; D000431:Ethanol; D013395:Sucrose