Alteration of the disruptive effect of fenfluramine on food consumption in the rat by repeated post-session administration of d-amphetamine

The purpose of this study was to determine whether repeated treatment (15 days) with d-amphetamine (AMP) or fenfluramine (FEN), administered after a daily 3 h feeding session (e. g. post-session), would result in tolerance or crosstolerance to the decrement in food consumption induced by treatment with either drug before feeding (e. g. pre-session). Groups of male rats were treated IP with 0.5 ml saline, 1.0, 2.0, or 4.0 mg/kg AMP, or 2.5, 5.0, or 10.0 mg/kg FEN prior to a 3 h feeding session. For the next 15 sessions, the respective groups were treated post-session with saline (0.5 ml), AMP (4.0 mg/kg), or FEN (10 mg/kg). Following the 15 day postsession phase, each group again received this pre-session treatment. The initial pre-session treatment with all dosages of these two drugs produced a significant decrease in food consumption. Tolerance to the food intake suppressant effect of FEN, but not AMP, resulted from repeated post-session treatment with the same agent. Repeated post-session treatment with AMP resulted in a significant decrement in the suppressant activity of FEN on food intake, whereas the corresponding post-session treatments with FEN did not alter the pre-session effects of AMP, except for an enhancement seen with higher AMP doses.