Supersensitive beta-adrenergic receptors are down-regulated in rat brain by mianserin administration

Experiments were undertaken to determine whether alterations in rat brain monoaminergic tone influence the manner in which mianserin administration modifies beta-adrenergic receptor function. Whereas the chronic administration of mianserin had little effect on isoproterenol-stimulated cAMP accumulation in control cerebral cortical slices, treatment with this antidepressant prevented or reversed beta-adrenergic receptor super-sensitivity resulting from reserpine or 6-hydroxydopamine administration. In contrast, 5,7 dihydroxytryptamine treatment had no effect on beta-adrenergic receptor activity, or on the ability of mianserin to modify isoproterenol-stimulated cAMP accumulation. The results indicate that antidepressant-induced alterations in beta-adrenergic receptor activity may, in some cases, be a function of receptor sensitivity at the time of drug administration.