NEUROENDOCRINE AND HYPOTHERMIC EFFECTS OF 5-HT1A RECEPTOR STIMULATIONWITH IPSAPIRONE IN HEALTHY-MEN - A PLACEBO-CONTROLLED STUDY

The neuroendocrine effects of 5-hydroxytryptamine-1A (5-HT1A) receptor stimulation remain uncertain in humans, in respect to both anterior a nd posterior pituitary hormone release. This is important because thes e endocrine responses are often used as indications of 5-HT1A receptor sensitivity. The link between receptor stimulation and subsequent hor mone release is more direct with posterior pituitary hormones because there is no intermediate hypothalamic peptide in the pathway. Theoreti cally, therefore, posterior pituitary hormones should be more valid in dicators of central 5-HT1A receptor sensitivity. We used the 5-HT1A re ceptor partial agonist ipsapirone (20 mg) as an oral serotonergic chal lenge drug in a random-order, double-blind placebo-controlled study of 12 healthy men. Blood sampling occurred at 30 min intervals up to 180 min after the administration of drug or placebo. Ipsapirone caused cl ear and significant elevations in adrenocorticotrophin (ACTH), cortiso l (CORT), prolactin (PRL), and growth hormone (GH) release. Peak hormo ne and ipsapirone blood levels both occurred at 60 min after ipsapiron e administration. Release of the posterior pituitary hormone oxytocin was also stimulated, but less robustly and with more baseline variatio n. Temperature fell significantly more after ipsapirone than placebo. These results contrast with previous studies, which found no effect of ipsapirone on PRL and GH release in humans, but are in accordance wit h data using other 5-HT1A agonist drugs. The presence of an oxytocin r esponse to ipsapirone suggests that oxytocin is a potential marker for serotonergic function in neuroendocrine challenge studies, but this a waits further study. (C) 1998 Rapid Science Ltd.