dl-Fenfluramine inhibits ethanol-induced ascorbic acid release in rat striatum studied by microdialysis

The effects of dl -fenfluramine, dl -5-hydroxytryptophan(5-HTP) and fluoxetine on ethanol-induced striatal ascorbic acid (AA) release in rat were studied by microdialysis coupled to high performance liquid chromatography with electrochemical detection. Ethanol (3.0 g/kg, i.p.) stimulated striatal AA release to more than 200% above the baseline. dl -Fenfluramine (20 mg/kg, i.p. or 40 mug/rat, i.c.v.), 10 min before ethanol administration, markedly inhibited ethanol-induced AA release. A similar result was also observed following dl -5-HTP (100 mg/kg, i.p.) administration. However, fluoxetine (10, 30 mg/kg, i.p.) showed no antagonistic effect on ethanol-induced AA release. The suppressing effect of dl -fenfluramine and dl -5-HTP on ethanolinduced AA release could be reversed by the 5-HT receptor antagonist cyproheptadine (10 mg/kg, s.c.). All these drugs had no effect on basal AA release. The results give a first evidence for the involvement of central serotonergic system, and suggest that differential activities may exist between dl -fenfluramine, dl -5-HTP and fluoxetine in regulating ethanol-induced AA release in rat striatum.