We investigated how the L-type calcium channel blockade (CCB) with nifedipine affects the cyclic AMP responses to noradrenaline or isoproterenol in cerebral cortical slices from rats receiving antidepressant treatments that induce (electroconvulsive shock, imipramine) or do not induce (amitriptyline) beta-downregulation. To assess the role of protein kinase C (PKC) in receptor crosstalk under CCB conditions, the cyclic AMP responses were tested also in the presence of a PKC activator, TPA. CCB alone induced no changes, but modulated the action of those antidepressants that down regulate the beta-adrenergic system. Chronic ECS and imipramine treatments were differently affected. ECS, under conditions of CCB, down regulated the response to isoproterenol in the presence of TPA, while imipramine ceased to block the TPA-potentiation of cyclic AMP responses. Thus, CCB affects the processes related to the antidepressant-induced changes on the crosstalk between alpha1- and beta-adrenergic receptors, depending on the specific properties of the antidepressant.