Effect of selective serotonin (5-HT) agonists and 5-HT₂ antagonist on prolactin secretion

The present study was undertaken to determine the involvement of serotonergic 5-HT₁ and 5-HT₂ receptor subtypes in stimulation of the secretion of prolactin. Several 5-HT agonists were administered, in a dose-response fashion, to conscious rats and the effect on the levels of prolactin in plasma was measured. The 5-HT_1A + 5-HT_1B agonist RU 24969 (5-methoxy-3[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole succinate) and the 5-HT₁ + 5-HT₂ agonist MK-212 (6-chloro-2-[1-piperazinyl]pirazine) increased levels of prolactin in plasma in a dose-dependent manner. In contrast, the selective 5-HT_1A agonists 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino]tetralin) and ipsapirone (2-[4-{4-(2-pyrimidinyl)-1-piperazinyl} butyl]-1,2-benzisothiazol-3-(2H)one-1,1-dioxidehydrochloride) did not increase levels of prolactin in plasma at any dose. The 5-HT-releasing drug, fenfluramine, also increased the concentration of prolactin in plasma. Pretreatment with the selective 5-HT₂ antagonist, LY53857 (6-methyl-1-[1-methylethyl]ergoline-8-carboxylic acid, 2-hydroxy-1-methyl propyl ester (Z)-2-butenedioate [1:1]), did not significantly diminish an increase in levels of prolactin in plasma, induced by injection of fenfluramine. The antagonist LY53857 inhibited, but did not block the MK-212- and RU 24969-induced increase in the levels of prolactin in plasma. By deduction, these data suggest that 5-HT_1B receptors, or as yet undefined 5-HT receptor subtypes may be involved in the stimulation of the secretion of prolactin by endogenously released 5-HT, and that 5-HT₂ receptors may play a minor role in the serotonergic regulation of the secretion of prolactin.