Differential effect of serotonin 5-HT(1A) receptor antagonists on the secretion of corticotropin and prolactin.

ABSTRACT

Serotonin (5-HT) participates in the neuroendocrine regulation of corticotropin (ACTH) and prolactin (PRL) secretion. We investigated the involvement of the 5-HT(1A) receptor in the mediation of ACTH and PRL response to the 5-HT(1A) receptor agonists 8-OH-DPAT and 5-HT, the 5-HT precursor 5-hydroxytryptophan (5-HTP) and restraint stress in male rats. Prior intracerebroventricular (i.c.v.) infusion of the 5-HT(1A) antagonists WAY-100635 and LY-206130 inhibited PRL and ACTH responses to i.c.v. infusion of 8-OH-DPAT, 5-HT as well as to 5-HTP administered systemically in combination with the 5-HT reuptake inhibitor fluoxetine (Flx). Infused i.c.v. NAN-190 inhibited the ACTH response to 8-OH-DPAT i.c.v. Intraperitoneal (i.p.) pretreatment with WAY-100635 inhibited ACTH and PRL responses to 8-OH-DPAT, whereas LY-206130 only inhibited the PRL response and NAN-190 had no effect. Injected i.p., the antagonists had no effect on 5-HT-induced hormone secretion, whereas the ACTH-stimulating effect of 5-HTP + Flx was increased by WAY and NAN. A 5-min restraint stress increased ACTH and PRL secretion; the ACTH, but not the PRL response to stress was inhibited by prior administration of WAY-100635 or LY-206130 either i.c.v. or i.p. NAN-190 had no effect on any stress response tested. It is concluded that (1) the three 5-HT(1A) antagonists used in our study have differential effects on stimulated hormone responses, (2) the antagonists exert different effects when administered systemically or centrally, and (3) the 5-HT(1A) receptor is involved in restraint stress-induced ACTH, but not PRL secretion.