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In Vivo Correlates of Central Serotonin Function after High‐Dose Fenfluramine Administration
Author(s) -
BAUMANN MICHAEL H.,
AYESTAS MARIO A.,
ROTHMAN RICHARD B.
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb08229.x
Subject(s) - fenfluramine , medicine , endocrinology , corticosterone , serotonin , prolactin , hypothalamus , saline , hormone , receptor
High doses of fenfluramine (FEN) are known to deplete central serotonin (5‐HT) in animals, but functional impairments associated with such 5‐HT depletion have been difficult to identify. In the present work, we examined neuroendocrine responsiveness in rats exposed to repeated high‐dose FEN treatment. Male rats fitted with indwelling catheters received FEN (20 mg/kg, subcutaneously, twice a day) or saline for 4 days. At 1 and 2 weeks after treatment, rats were challenged with intravenous FEN (1.5 & 3 mg/kg) or saline. Repeated blood samples were drawn, and plasma was assayed for prolactin and corticosterone by radioimmunoassay. Acute FEN challenge caused dose‐dependent elevations of plasma prolactin and corticosterone in all rats. However, the FEN‐induced hormone responses were significantly blunted ( p <0.01) in rats previously exposed to FEN. The repeated FEN dosing regimen dramatically reduced (>50%) postmortem 5‐HT levels in the mediobasal hypothalamus, basolateral amygdala, and hippocampus, while the lateral hypothalamus was unaffected. These data suggest that high‐dose FEN causes alterations in central 5‐HT systems involved with pituitary hormone secretion. The relevance of the present data to the clinical use of FEN is unclear. Because the neuroendocrine challenge paradigm is able to identify functional 5‐HT deficits in rats, we propose that similar experiments should be performed in humans. Neuroendocrine challenge tests represent a reliable method to test the existence of FEN‐induced neurotoxicity in human patients undergoing long‐term FEN treatment.