Gender-dependent dissociation between oxytocin but not ACTH, cortisol or TSH responses to m-chlorophenylpiperazine in healthy subjects.
m-Chlorophenylpiperazine (m-CPP), a serotonin (5-HT) agonist with some selectivity for the 5-HT2C receptor subtype, which is widely used to examine 5-HT receptor function in human subjects, has been found to induce oxytocin and thyrotropin (TSH) responses in rodents. This study examined whether m-CPP had any effect on plasma oxytocin, TSH and aldosterone concentration in healthy volunteers using a double-blind, placebo-controlled crossover design. Plasma adrenocorticorticotropic hormone (ACTH) and cortisol responses, two generally accepted markers of m-CPP-induced 5-HT receptor activation, were measured in parallel. Male subjects (n=7) received placebo, 0.25 and 0.5 mg/kg oral m-CPP. In female subjects (n=5), the effects of placebo and 0.25 mg/kg m-CPP were studied. After placebo, given in the morning, ACTH, cortisol, TSH and aldosterone concentrations decreased over time. m-CPP 0.25 mg/kg avoided decreases in ACTH, cortisol and TSH concentrations; these responses were significant. At the dose of 0.5 mg/kg, m-CPP caused increase in ACTH, cortisol, TSH and aldosterone concentrations. Significant plasma oxytocin responses were found in female subjects only; thus this effect of m-CPP was statistically significantly gender dependent. Other responses to m-CPP were similar in male and female subjects. The present results suggest that there are clear differences, including dose and gender-dependent dissociations, among the 5-HT receptor agonist m-CPP-induced neuroendocrine responses.
Bagdy
G
G
Laboratory of Neurochemistry and Experimental Medicine, National Institute of Psychiatry and Neurology, Budapest, Hungary.
Arato
M
M
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000450:Aldosterone / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D010121:Oxytocin / Q000097:blood*; D010879:Piperazines / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012737:Sex Factors; D013972:Thyrotropin / Q000097:blood*
D010879:Piperazines; D017366:Serotonin Receptor Agonists; D000450:Aldosterone; D010121:Oxytocin; D000324:Adrenocorticotropic Hormone; D013972:Thyrotropin; C015068:1-(3-chlorophenyl)piperazine; D006854:Hydrocortisone