Pindolol pretreatment blocks stimulation by meta-chlorophenylpiperazine of prolactin but not cortisol secretion in normal men.
Previous reports from this laboratory have shown that pindolol, a partial serotonin1A receptor agonist, inhibited prolactin, but not cortisol secretion induced by administration of the serotonin (5-HT) precursor L-5-hydroxytryptophan or the direct-acting 5-HT2A/5HT2C receptor agonist MK-212. The findings suggest additive or interactive effects of 5-HT1A and 5-HT2A/5-HT2C receptors in modulating 5-HT-related prolactin, but not cortisol, responsivity. To examine further the role of 5-HT1A and 5-HT2A/5-HT2C receptors in prolactin and cortisol secretion in healthy men, the effects of meta-chlorophenylpiperazine (mCPP), a potent 5-HT receptor agonist, on the above hormones were studied in eight healthy men with and without pindolol pretreatment. It has previously been demonstrated that ketanserin, a 5-HT2A antagonist, and ritanserin, a 5-HT2A/5-HT2C antagonist, block the prolactin and attenuate the hypothalamic-pituitary-adrenal axis responses to mCPP in man or rodents. Administration of mCPP induced a significant increase in plasma concentrations of prolactin and cortisol. The mCPP-induced prolactin concentrations were significantly blocked by pretreatment with pindolol, whereas mCPP-stimulated cortisol levels were not diminished by pindolol pretreatment. Thus, mCPP-induced prolactin secretion appears to require the availability of both 5-HT2C and 5-HT1A receptor activation, since blockade of either of these receptors may diminish the mCPP-induced prolactin response. Cortisol secretion stimulated by mCPP may occur following 5-HT2C receptor stimulation in the presence of 5-HT1A receptor blockade.
Meltzer
H Y
HY
Department of Psychiatry, Case Western Reserve University, School of Medicine, University Hospitals of Cleveland, OH 44106, USA.
Maes
M
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D010869:Pindolol / Q000494:pharmacology*; D010879:Piperazines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011388:Prolactin / Q000097:blood*; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects; D012016:Reference Values; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D016037:Single-Blind Method
D000319:Adrenergic beta-Antagonists; D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D011388:Prolactin; D010869:Pindolol; C015068:1-(3-chlorophenyl)piperazine; D006854:Hydrocortisone