5,7-Dihydroxytryptamine-induced lesions of serotonergic neurons and desipramine-induced down-regulation of cortical beta adrenoceptors: a re-evaluation.

Studies on mechanisms of desipramine (DMI) induced desensitization of the norepinephrine (NE) receptor coupled adenylate cyclase system in brain have shown that the endogenous agonist NE plays a pivotal role for both the development of subsensitivity and the down-regulation of beta adrenoceptors [l-4]. Moreover, an intact serotonergic neuronal input is co-required for the down-regulation of central beta adrenoceptors by tricyclic antidepressants [5-71, monoamine oxidase (MAO) inhibitors, and electroconvulsive treatment [8]. In animals with a reduced synaptic availability of serotonin (WIT), cortical beta adrenoceptors display a marked decrease in agonist affinity as determined in competition-binding studies [9, lo], with no significant changes occurring in the Kd values of antagonist binding. Since the previously reported lcso values for isoproterenol were derived from rather shallow displacement curves [9] and the density of beta adrenoceptors was determined by Scatchard analysis of antagonist binding, information on high and low agonist affinity of beta adrenoceptors is desirable but not available. Consequently, we have re-evaluated the effect of chronic treatment with DMI and of specific lesions of serotonergic neurons with 5,7dihydroxytryptamine (5,7-DHT) on beta adrenoceptors in rat cortex by using non-linear regression analysis of competition-binding curves.