Bk. Koe et La. Lebel, EFFECTS OF SEROTONINERGIC AGENTS ON DOWN-REGULATION OF BETA-ADRENOCEPTORS BY THE SELECTIVE SEROTONIN REUPTAKE INHIBITOR SERTRALINE, Archives internationales de pharmacodynamie et de therapie, 329(2), 1995, pp. 231-244
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.