Effects of serotonin antagonists on the performance of a simple food acquisition task in rats treated with fenfluramine isomers.

The effect of fenfluramine on food-rewarded runway behaviour was studied in rats that had reached stable performance levels in a three-trials test procedure. d-Fenfluramine was about twice as potent as 1-fenfluramine in its influence on all aspects of runway behaviour: starting speed, running speed and the number of pellets eaten in each trial. Blockade of peripheral serotonin receptor sites by pretreatment with xylamidine, at a dose (2 mg/kg) blocking serotonin-induced inhibition of food intake, was unable to counteract the decrease in runway performance that resulted from treatment with either 2.5 mg/kg d-fenfluramine or 5.0 mg/kg 1-fenfluramine. However pretreatment with metergoline (2 mg/kg), an antagonist that affects both central and peripheral receptor sites, improved the performance of rats given these doses of d- and 1-fenfluramine. It is concluded that both isomers of fenfluramine affect food-rewarded runway behaviour through a mechanism that involves the stimulation of central but not peripheral serotoninergic pathways.