OBJECTIVE: The authors examined serotonergic-mediated prolactin release in bipolar mania, using d-fenfluramine as a probe. METHOD: Hospitalized patients with bipolar disorder, currently manic, were matched for age and sex to healthy comparison subjects. Each group consisted of nine subjects (seven men and two women). After an overnight fast, all subjects had an intravenous cannula inserted into a forearm at 8:30 a.m., and baseline blood samples for determination of prolactin and cortisol levels were drawn. d-Fenfluramine (30 mg p.o.) was then administered; plasma prolactin levels were measured 15 minutes before d- fenfluramine was given, immediately before, and 60, 120, 180, 240, and 300 minutes afterward. RESULTS: Baseline serum cortisol levels were higher in the bipolar manic subjects than in the comparison subjects, although baseline prolactin levels were similar in the two groups. The plasma prolactin responses to d-fenfluramine of the bipolar manic subjects were significantly lower than those of the comparison subjects. CONCLUSIONS: Bipolar mania appears to be associated with a state of decreased serotonergic responsivity similar to that found in unipolar depression.Abstract Teaser