Preliminary findings with the indirect 5-HT agonist dexfenfluramine on heroin discrimination and self-administration in rats.

In the present study, the effect of the 5-HT releaser/reuptake inhibitor dexfenfluramine in heroin self-administration and morphine (3 mg/kg) drug discrimination paradigms was examined. Dexfenfluramine (1 mg/kg) reduced heroin self-administration (heroin dose 0.03 mg/kg/infusion; FR5 schedule; 1-h session/day). This effect was antagonised by the 5-HT1/2 receptor antagonist metergoline (1 mg/kg). In the drug discrimination model, dexfenfluramine (0.5-2.5 mg/kg) produced no significant generalisation to a morphine cue, and also failed to modify the generalization curve to heroin. Dexfenfluramine (1 mg/kg) produced a slight decrement in response rate in the drug discrimination model and this effect was potentiated by heroin. The mechanism(s) by which dexfenfluramine reduces heroin self-administration remain to be determined, however substitution for heroin would seem unlikely. Furthermore, this effect of dexfenfluramine is probably mediated by either 5-HT1 or 5-HT2 receptors.