EFFECTS OF SEROTONINERGIC AGENTS ON DOWN-REGULATION OF BETA-ADRENOCEPTORS BY THE SELECTIVE SEROTONIN REUPTAKE INHIBITOR SERTRALINE

The results of the present study show that the downregulation of beta- adrenoceptors of rat brain, induced by subacute administration of sert raline, is facilitated when this selective serotonin reuptake inhibito r was co-administered with the serotonin releaser, norfenfluramine, or the serotonin terminal autoreceptor antagonist, methiothepin. The res pective drug combination produced a reduction in B-max of [H-3]dihydro alprenolol binding to cortical membranes of treated rats at a dose of the releaser, release enhancer, or sertraline, which was ineffective w hen administered alone. In a similar manner, the 5-HT1A agonists, gepi rone and 8-OH-DPAT, were found to facilitate the downregulation of bet a-adrenoceptors induced by sertraline. The 5-HT1B agonist, 3-trifluoro methylphenylpiperazine, and the 5-HT2 antagonist, ritanserin, showed n either facilitation nor antagonism of sertraline, but the 5-HT3, antag onist, ondansetron, attenuated the decrease of B-max of [H-3]dihydroal prenolol binding elicited by sertraline. Agents that putatively increa se the serotoninergic activity facilitated the downregulation of beta- adrenoceptors induced by sertraline, suggesting that the enhancement o f serotonin transmission, expected of the selective serotonin reuptake inhibitor itself, may play a role in this effect of sertraline. Wheth er the downregulation of brain beta-adrenoceptors by sertraline plays any role in its antidepressant activity cannot be deduced from these e xperiments.