Further studies to examine the nature of dexfenfluramine-induced suppression of heroin self-administration.

The present series of experiments sought to investigate further the mechanism by which dexfenfluramine, a selective 5-HT releaser/reuptake inhibitor, reduces heroin self-administration by male Wistar rats. In experiment 1, the effect of combined intravenous heroin and intraperitoneal dexfenfluramine injections on operant responding for food was examined. In experiment 2, the maintenance of dexfenfluramine suppression of heroin self-administration following chronic (7 day) treatment was evaluated. Finally, in experiment 3, the ability of various 5-HT antagonists to block the dexfenfluramine suppression was examined. The results from experiment 1 suggest that sensorimotor deficits/malaise potentially associated with heroin/dexfenfluramine combinations are unlikely to account for the reductions in heroin self-administration. Experiment 2 suggested that the suppressant effect of dexfenfluramine on heroin responding may diminish rapidly following chronic treatment. Finally, central 5-HT1 and/or 5-HT2, but not 5-HT3, receptors may underlie the suppressant effects of dexfenfluramine on heroin self-administration.