title: The GABA(B) receptor allosteric modulator CGP7930, like baclofen, reduces operant self-administration of ethanol in alcohol-preferring rats.
abstract: GABA systems have been implicated as targets for ethanol at the cellular, molecular and behavioural level. The present study was designed to further examine the potential of the GABA(B) receptor as a target for regulating operant alcohol responding. Given that the prototypic agonist, baclofen, reduces the self-administration of alcohol, we hypothesized that the GABA(B) receptor allosteric modulator, CGP7930, might have similar actions but a reduced side-effect profile. In this context, inbred alcohol-preferring (iP) rats were trained to respond for 10% v/v ethanol in a fixed ratio paradigm; all drug testing was performed under an FR3 schedule. Both baclofen and CGP7930 independently reduced voluntary responding for 10% ethanol in a dose-related manner. Neither drug impacted upon responding for water. A combination of subthreshold doses of baclofen and CGP7930 was also able to reduce operant responding for ethanol, suggesting that CGP7930 is indeed acting to facilitate GABA(B) receptor-mediated signalling in this paradigm. These data demonstrate the potential of positive allosteric modulators of metabotropic GABA(B) receptors to regulate alcohol responding.
authors.affiliation: Department of Neuropharmacology, National Institute of Drug Dependence, University of Peking, Beijing, P.R. China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Liang
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Elena
authors.initials: E
authors.lastname: Krstew
authors.forename: Michael S
authors.initials: MS
authors.lastname: Cowen
authors.forename: Fiona Y
authors.initials: FY
authors.lastname: Carroll
authors.forename: Duncan
authors.initials: D
authors.lastname: Crawford
authors.forename: Philip M
authors.initials: PM
authors.lastname: Beart
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage; D001522:Behavior, Animal; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage*; D018757:GABA Modulators / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage*; D051381:Rats; D012646:Self Administration / Q000379:methods; D013997:Time Factors
chemical_list: C438607:2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol; D002492:Central Nervous System Depressants; D018757:GABA Modulators; D010636:Phenols; D000431:Ethanol; D001418:Baclofen