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Previously we reported that 5 min after intracerebroventricular (i.c.v.) injection, serotonin (5-HT, 2.5 micrograms) produced increases in blood pressure and decreases in heart rate in conscious rats that were blocked by LY 53857 (a selective 5-HT2/1C antagonist) and were sensitive to vasopressin antagonism. The present studies were performed to determine if this dose of 5-HT acts similarly to increase plasma vasopressin levels. In addition, the vasopressin responses were compared to prolactin, corticosterone, and plasma renin activity, three other neuroendocrine systems regulated in part by 5-HT. The administration of 5-HT (2.5 micrograms i.c.v.) produced a rapid (maximum response in less than 5 min) and brief (return to baseline by 15 min) increase in plasma vasopressin levels. The response was eliminated by the centrally acting 5-HT2/1C antagonist LY 53857 (100 micrograms/kg i.v.), but only attenuated by xylamidine (100 micrograms/kg i.v.), a 5-HT2/1C antagonist that reportedly does not cross the blood-brain barrier. 5-HT also increased plasma prolactin and corticosterone levels, but neither LY 53857 nor xylamidine altered these responses. In rats rendered chronically baroreceptor deficient by sinoaortic deafferentation, the vasopressin response to 5-HT was reduced, whereas the prolactin response was normal. 5-HT did not increase plasma renin activity in intact or baroreceptor-deficient rats, in contrast to the other neuroendocrine systems studied. Thus, the data demonstrate that vasopressin levels are elevated briefly following 5-HT i.c.v., consistent with the pharmacologic profile of the early cardiovascular response.