The high preference for alcohol intake observed in Fawn-Hooded rats has been attributed to the central serotonin (5-HT) dysfunction in this strain. To further characterize the involvement of 5-HT in alcohol-seeking behavior in Fawn-Hooded rats, the effect of both acute and subchronic administration of fenfluramine, a 5-HT releaser, on alcohol intake and preference was determined. Rats were individually housed and provided free access to a solution of 10% alcohol, food, and water. After establishing a stable baseline, rats were injected twice daily for 1 day or for 5 consecutive days either with saline or 0.1, 0.25, 0.5, and 1.0 mg/kg of fenfluramine at 0930 h and 1600 h, and their consumption of alcohol, food, and water was measured for 24 h. Another group of rats scheduled with a limited access (1 h/day) to alcohol and free access to food and water were injected with either saline or 0.25, 0.5, 0.75, and 1.0 mg/kg fenfluramine 20 min before exposure to alcohol, and their alcohol consumption was measured at the end of 1 h exposure. Further, to determine the effect of fenfluramine on alcohol metabolism, rats were injected with 1.0 mg/kg fenfluramine or saline and 15 min later with 2.5 g/kg alcohol (16%, v/v). Blood alcohol levels were then measured at 1, 3, and 5 h after alcohol administration. Our results demonstrate that both acute and subchronic administration of fenfluramine dose-dependently attenuate alcohol intake and increased water intake without a significant effect on food intake. Fenfluramine did not affect the pharmacokinetics of alcohol, indicating a central effect.(ABSTRACT TRUNCATED AT 250 WORDS)