Differential effect of serotonin 5-HT(1A) receptor antagonists on the secretion of corticotropin and prolactin.
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.
Jørgensen
H
H
Department of Medical Physiology, Rigshospitalet, University of Copenhagen, Denmark. hsj@mfi.ku.dk
Kjaer
A
A
Warberg
J
J
Knigge
U
U
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003514:Cyclohexylamines / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012149:Restraint, Physical; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013312:Stress, Physiological / Q000378:metabolism
D003514:Cyclohexylamines; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C098407:LY 206130; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D006916:5-Hydroxytryptophan