Interactions between iboga agents and methamphetamine sensitization: studies of locomotion and stereotypy in rats

Rationale: The phenomenon of sensitization has been theoretically implicate d in mediating various aspects of drug addiction. Recent dose-response stud ies demonstrated that pretreatment with the putative anti-addictive agent, ibogaine (IBO), and a synthetic iboga alkaloid congener, 18-methoxycoronari dine (18-MC), increase the potency of cocaine to elicit behavioral sensitiz ation, an effect proposed to contribute, in part, to their ability to atten uate drug self-administration. Objectives: As abuse of the methylated amphe tamine derivative, methamphetamine (METH), is a growing public health conce rn, the present study determined the interactions between IBO and 18-MC and the expression of METH-induced behavioral sensitization. Methods: The effe cts of pretreatment with 18-MC (40 mg/kg, IP, 19 h earlier) on the expressi on of METH-induced locomotion (0, 0.25, 0.5, 1 and 2 mg/kg, IP) and the eff ects of pretreatment with either IBO or 18-MC on the expression of METH-ind uced stereotypy (2 and 4 mg/kg, IP) were assessed in rats treated chronical ly with either METH (4 mg/kg daily for 7 days) or saline. Results: Compared to vehicle-pretreated controls, 18-MC produced an overall enhancement in M ETH-induced locomotion in rats treated chronically, but not acutely, with M ETH. In addition, both iboga agents increased the stereotypic response to M ETH. Conclusions: Iboga agents augment both the locomotor and stereotypic e ffects of METH in a manner consistent with previous reports for cocaine. Th us, it appears that iboga agents interact in a similar manner with the neur al mechanisms mediating motor hyperactivity induced by the chronic administ ration of stimulant drugs.