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.

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.