Carbamazepine (CBZ), an anticonvulsant, has beeen reported to displace ligands at adenosine receptors. Several studies have demonstrated that as far as A2 adenosine receptors is concerned, CBZ acts as an antagonist. However, the situation with regard to A1 receptors is less straightforward. In this study, we describe the effects of one-week CBZ treatment (25 mg/kg/day) on cerebrocortical A1 adenosine receptors. A1 adenosine receptor bindings as determined by using [3H]DPCPX was not significantly altered in membranes prepared from CBZ-treated rats. However, there was a significant decrease in the A1 adenosine receptor-mediated stimulation of [35S]GTPγS binding to cerebrocortical membranes prepared from CBZ-treated rats (20.0% decrease in basal activity; 17.8% decrease in maximal activity). The basal and 10-4 M forskolin-stimulated adenylyl cyclase activities were relatively unaffected by CBZ treatment, but 10 mM NaF-stimulated adenylyl cyclase activity was significantly reduced in CBZ-treated rats. It appears that one-week CBZ treatment caused an uncoupling of adenosine receptors from G proteins without alteration of A1 adenosine receptor molecules, suggesting that CBZ acts as an agonist at A1 adenosine receptors in rat brain.