Enhanced adenylate cyclase activity in neonatally dopamine lesioned rats is related to increased Gs-protein coupling

It has previously been shown that neonatal selective lesions of the central dopamine system with 6-hydroxydopamine lead to increased basal and dopamine-stimulated adenylate cyclase activity in striatum without any alterations of dopamine receptor binding characteristics. In the present study, it was shown that adenylate cyclase activity following G-protein stimulation by the GTP analogue 5-guanylimidodiphosphate (Gpp(NH)p) was increased in striatal preparations from neonatally 6-hydroxy-dopamine-lesioned rats, compared with control animals. No difference was seen in forskolin-stimulated enzyme activity between the two groups. These results indicate that neonatal dopamine lesions induce a selective functional supersensitivity at the D1 receptor complex by enhancing the coupling efficiency of the Gs protein to adenylate cyclase, without alterating the catalytic activity of the enzyme.