Characterization of the depression of rat cerebral cortical neurons by selective adenosine agonists

The identity of the receptors involved in mediating the depressant actions of adenosine and its analogs on the spontaneous firing of rat cerebral cortical neurons was elucidated by evaluating the effects of selective A1 and A2 receptor agonists and antagonists. The A1 agonist N6-cyclopentyladenosine (CPA) and the A2 agonist CGS 21680 both depressed cortical neuronal firing. At low doses (0.001-0.01 mg/kg) the A1 antagonist DPCPX blocked the effects of CPA, but not those of CGS 21680. At higher doses, it antagonized both agonists. The A2 antagonist CGS 15943 (0.01-0.1 mg/kg) selectively blocked the actions of CGS 21680. At 1 mg/kg it also antagonized the responses of some neurons to CPA. These results suggest that the depressant actions of adenosinergic agonists on the firing of rat cerebral cortical neurons involve both A1 and A2 receptors.