In vivo evidence that GABA(B) receptors are negatively coupled to adenylate cyclase in rat striatum

The characteristics of the cerebral GABA(B) receptor/cyclic AMP (cAMP)-generating system were investigated using the in vivo microdialysis technique in freely moving rats. Addition of forskolin, an activator of adenylate cyclase, to perfusate for 20 min resulted in a dose-dependent increase of cAMP efflux from the striatum. Pre- and coinfusions of baclofen for 80 min had no effect on the basal efflux of cAMP from the striatum but induced a significant decrease of forskolin (10 microM)-stimulated cAMP efflux from the striatum in a dose-dependent manner. SKF 97541 (100 microM), a GABA(B) receptor agonist, and GABA (50 microM) also decreased forskolin-induced cAMP efflux from the striatum. Coinfusion of CGP 54626A (100 microM), a GABA(B) receptor antagonist, counteracted the effect of baclofen on the forskolin-stimulated cAMP efflux. In contrast, the isoproterenol (5 mM)-induced increase of cAMP efflux from the striatum was significantly enhanced by pre- and coinfusions with baclofen. These results suggest that this test system using in vivo microdialysis may be useful for examining the effect of drugs on the GABA(B) receptor-linked cAMP-generating system in vivo.