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.