Fenfluramine and brain transmitters in the obese Zucker rat

Genetically obese Zucker rats and their lean litter mates were treated for 5 days with fenfluramine. Levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) and their metabolism were assayed in the hypothalamus, striatum, medulla-oblongata pons and remainder of the brain. Fenfluramine induced a slight increase in the level of NE in the hypothalamus in lean rats and a marked decrease in obese rats. No change in the synthesis of NE was found. Fenfluramine had no effect on the level and metabolism of DA. The levels of 5-HT were decreased by fenfluramine in obese and lean rats, and the metabolism was increased. The levels of GABA were not changed by fenfluramine. Synthesis of GABA was increased in the remainder of the brain of obese and lean rats. These data suggest that fenfluramine acts on 5-HT systems in both obese and lean rats and are consistent with reports of the pharmacological effects of fenfluramine.