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 inhibit or 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 discrimin ation model, dexfenfluramine (0.5-2.5 mg/kg) produced no significant g eneralisation to a morphine cue, and also failed to modify the general ization curve to heroin. Dexfenfluramine (1 mg/kg) produced a slight d ecriment in response rate in the drug discrimination model and this ef fect was potentiated by heroin. The mechanism(s) by which dexfenfluram ine reduces heroin self-administration remain to be determined, howeve r substitution for heroin would seem unlikely. Furthermore, this effec t of dexfenfluramine is probably mediated by either 5-HT1 or 5-HT2 rec eptors.