Differential development of tolerance to the effects of d-amphetamine and fenfluramine on food intake in baboons.

Food intake of six adult male baboons (Papio cynocephalus anubis) was monitored during daily 22-hr experimental sessions. Food was available under a chain schedule with two components. After completion of the first "procurement component" response requirement, access to food, i.e., a meal, became available under the second "consumption component," during which each response produced a 1-g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. Complete dose-response functions for amphetamine and fenfluramine were determined before, during and after a period of repeated administration of each drug. On the first day of repeated administration both drugs decreased intake during both the first 8 hr and the entire session to 65% of baseline. Total intake returned to 93% of baseline during repeated amphetamine, but only to 76% of baseline during repeated fenfluramine. There was no recovery of intake, however, during the first 8 hr of the session. Baboons given repeated amphetamine were tolerant to the food intake decreasing effects of acute amphetamine, but not acute fenfluramine. Baboons given repeated fenfluramine did not develop tolerance to the effects of fenfluramine or amphetamine on food intake. The absence of cross-tolerance or increased sensitivity between amphetamine and fenfluramine suggests that although both serotonergic and dopaminergic systems are involved in feeding, they can influence food intake independently.