Fenfluramine discrimination in obese and lean Zucker rats: serotonergic mediation of effect

Genetically obese Zucker rats and their lean littermates were trained to discriminate between the stimulus properties of 2.0 mg/kg fenfluramine and its vehicle in a two-lever, food-motivated operant task. Both groups learned the discrimination at the same rate and all rats showed a dose-related decrease in discriminative performance with lower fenfluramine doses. Analysis of the dose-response curves indicated an ED50 for the obese rats of 0.56 mg/kg and for the lean group of 0.42 mg/kg. Time-course experiments indicted that the obese rats maintain errorless discrimination through 90 min post-injection but discriminate significantly less than the lean rats at 960 min post-administration. These results suggest a similar sensitivity to fenfluramine in obese and lean rats with a difference in the time-course of drug action. Pre-treatment with the specific serotonin receptor antagonist pirenperone significantly attenuated fenfluramine discrimination in lean rats without a similar effect in the obese rats. Possible reasons for this observation are offered.