Effects of various serotonin receptor subtype-selective antagonists alone and on m-chlorophenylpiperazine-induced neuroendocrine changes in rats.
Administration of m-chlorophenylpiperazine [m-CPP, a serotonin (5-HT) agonist] to rats increases plasma concentrations of prolactin and corticosterone. Pretreatment with various doses of ritanserin (5-HT1C/5-HT2 antagonist), ICS 205-930 and MDL-72222 (5-HT3 antagonists), iodocyanopindolol or CG361A (beta adrenoceptor antagonists) and spiperone (5-HT1A/5-HT2 antagonist) did not attenuate m-CPP-induced increases in plasma concentrations of prolactin. In contrast, pretreatment with various doses of metergoline (5-HT1/5-HT2 antagonist), propranolol (beta adrenoceptor antagonist that also has binding affinity for 5-HT1A, 5-HT1B and 5-HT1C sites), mesulergine and mianserin (5-HT1C/5-HT2 antagonists) attenuated m-CPP-induced increases in plasma prolactin. On the other hand, m-CPP-induced increases in corticosterone concentrations were attenuated only by pretreatment with a low dose of mianserin and a high dose of spiperone. When administered without m-CPP, metergoline, mesulergine, ritanserin, ICS 205-930 and high doses of mianserin, spiperone and propranolol increased plasma corticosterone secretion. On the other hand, none of the antagonists used in the present study, except spiperone, had any significant effect on plasma prolactin secretion. These findings suggest that m-CPP-induced prolactin secretion is mediated by stimulation of 5-HT1C receptors while corticosterone secretion may be mediated either by an antagonistic effect at 5-HT3 receptor subtype or by nonserotonergic mechanisms. Alternatively, enhancement of corticosterone secretion by the 5-HT antagonists when administered alone may be responsible for their failure to block m-CPP-induced corticosterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Aulakh
C S
CS
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland.
Hill
J L
JL
Murphy
D L
DL
D000818:Animals; D003345:Corticosterone / Q000097:blood*; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D008803:Mianserin / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology
D004873:Ergolines; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; D008711:Metergoline; D008803:Mianserin; D013134:Spiperone; D011388:Prolactin; C015068:1-(3-chlorophenyl)piperazine; C031649:mesulergine; D003345:Corticosterone