Differential effect of serotonin 5-HT1A receptor antagonists on the secretion of corticotropin and prolactin

Serotonin (5-HT) participates in the neuroendocrine regulation of corticotr opin (ACTH) and prolactin (PRL) secretion. We investigated the involvement of the 5-HT1A receptor in the mediation of ACTH and PRL response to the 5-H T1A receptor agonists 8-OH-DPAT and 5-HT, the 5-HT precursor 5-hydroxytrypt ophan (5-HTP) and restraint stress in male rats. Prior intracerebroventricu lar (i.c.v.) infusion of the 5-HT1A antagonists WAY-100635 and LY-206130 in hibited PRL and ACTH responses to i.c.v. infusion of 8-OH-DPAT, 5-HT as wel l as to 5-HTP administered systemically in combination with the 5-HT reupta ke inhibitor fluoxetine (Flx). Infused i.c.v. NAN-190 inhibited the ACTH re sponse to 8-OH-DPAT i.c.v, Intraperitoneal (i.p.) pretreatment with WAY-100 635 inhibited ACTH and PRL responses to 8-OH-DPAT, whereas LY-206130 only i nhibited the PRL response and NAN-190 had no effect, Injected i.p., the ant agonists had no effect on 5-HT-induced hormone secretion, whereas the ACTH- stimulating effect of 5-HTP + Fix was increased by WAY and NAN. A 5-min res traint stress increased ACTH and PRL secretion; the ACTH, but not the PRL r esponse 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 (I)the three 5-HT1A antagonists used in our st udy have differential effects on stimulated hormone responses, (2) the anta gonists exert different effects when administered systemically or centrally , and (3) the 5-HT1A receptor is involved in restraint stress-induced ACTH, but not PRL secretion. Copyright (C) 2001 S. Karger AG, Basel.