Sertraline, a selective inhibitor of serotonin uptake, induces subsensitivity of β-adrenoceptor system of rat brain

Subacute administration (b.i.d. for 4 days) of sertraline, a potent and selective inhibitor of serotonin uptake, was found to reduce cyclic AMP generation by the norepinephrine receptor-coupled adenylate cyclase in rat limbic forebrain slices and decrease the number of β-adrenoceptors in rat cerebral cortex without affecting the affinity of [ 3H]dihydroalprenolol binding. Co-administration of sertraline and the serotonin agonist, quipazine, at doses at which neither agent had an effect, resulted in desensitization of norepinephrine receptor-coupled adenylate cyclase and down-regulation of β-adrenoceptors. These findings suggest that increased serotonergic activity may be involved in the induction of subsensitivity of the β-adrenoceptor system of rat brain by sertraline.