We investigated the effect of prolonged electroconvulsive shock (ECS) or imipramine treatment on cyclic AMP accumulation induced by ibotenate and glutamate in rat cerebral cortical slices. Prolonged imipramine or electroconvulsive shock treatment attenuated the ibotenate-induced increase in cyclic AMP accumulation and inhibited the synergistic interaction between ibotenate and noradrenaline; the glutamate-mediated inhibition of forskolin-stimulated cyclic AMP accumulation was not modified. Our results indicate that multiple effects of excitatory amino acids on cyclic AMP accumulation are modified differently by antidepressant treatment.