The interaction of dopaminergic and serotonergic drugs on plasma prolactin in ovariectomized, estrogen-treated rats

Pharmacologic agents that either block or stimulate dopaminergic or block serotonergic receptors were administered intraarterially alone or in combination to ovariectomized, estrogen-treated rats. Prolactin was estimated by radioimmunoassay of plasma collected by serial blood sampling from chronic aortic catheters. Apomorphine (10 mg/kg) depressed, whereas Pimozide (50 and 250 mug/kg) and Methiothepin (50, 500 and 5000 mug/kg) markedly increased prolactin levels. Apomorphine completely blocked the increases induced by the lowest does of Pimozide and Methiothepin, as well as the initial increases at the higher doses. However, at later time intervals after large doses of Pimozide and Methiothepin in apomorphine-pretreated rats there was a marked rebound of prolactin which was greater than the level induced by each drug alone. The serotonin antagonists SQ 10,631 and methysergide reduced the Pimozide-induced elevation in prolactin levels, suggesting that part of the increase in prolactin following dopaminergic blockage may result from the action of a tonically stimulatory serotonin system that is normally masked by the intense tonic inhibition by the dopaminergic system.