Reduced G-protein coupling to the GABA_B receptor in the nucleus accumbens and the medial perfrontal cortex of the rat after chronic treatment with nicotine

The effect of repeated administration of nicotine (0.4 mg/kg, daily, s.c., for 14 days) on GABA(B) receptor density, affinity and G-protein coupling was investigated in the mesocorticolimbic system of the rat brain. Baclofen-stimulated [S-35]GTPgammaS binding autoradiography revealed that the level of G-protein coupling to GABA(B) 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, GABA(B) receptor density and affinity, as revealed by [H-3]GABA saturation binding autoradiography, were not altered by the nicotine exposure in any of the regions examined. Reduced G-protein coupling to the GABA(B) receptor may result in disinhibition of mesocorticolimbic dopaminergic neurones, which would contribute to the development of sensitised dopaminergic responses to repeated administration of nicotine. (C) 2003 Elsevier Ireland Ltd. All rights reserved.