title: Reduced G-protein coupling to the GABAB receptor in the nucleus accumbens and the medial prefrontal cortex of the rat after chronic treatment with nicotine.
abstract: The effect of repeated administration of nicotine (0.4 mg/kg, daily, s.c., for 14 days) on GABAB receptor density, affinity and G-protein coupling was investigated in the mesocorticolimbic system of the rat brain. Baclofen-stimulated [35S]GTPgammaS binding autoradiography revealed that the level of G-protein coupling to GABAB receptors was significantly reduced in the medial prefrontal cortex and the nucleus accumbens of nicotine-treated rats as compared to vehicle-injected controls. By contrast, GABAB receptor density and affinity, as revealed by [3H]GABA saturation binding autoradiography, were not altered by the nicotine exposure in any of the regions examined. Reduced G-protein coupling to the GABAB receptor may result in disinhibition of mesocorticolimbic dopaminergic neurones, which would contribute to the development of sensitised dopaminergic responses to repeated administration of nicotine.
authors.affiliation: Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. diana_amantea@yahoo.co.uk
authors.forename: Diana
authors.initials: D
authors.lastname: Amantea
authors.forename: Michela
authors.initials: M
authors.lastname: Tessari
authors.forename: Norman G
authors.initials: NG
authors.lastname: Bowery
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism*
chemical_list: D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D009538:Nicotine; D019204:GTP-Binding Proteins; D001418:Baclofen