Interactions between iboga agents and methamphetamine sensitization: studies of locomotion and stereotypy in rats.
K K Szumlinski, M Y Balogun, I M Maisonneuve, S D Glick
Psychopharmacology August 1, 2000 DOI: 10.1007/s002130000478 via PubMed
Summary
AI-generated from the abstractIbogaine and 18-methoxycoronaridine (18-MC), compounds being studied as potential treatments for addiction, increased the behavioral effects of methamphetamine in rats. Rats given methamphetamine daily for seven days and then pretreated with 18-MC showed more movement in response to methamphetamine than those given a placebo. Both ibogaine and 18-MC also intensified repetitive, stereotypic behaviors caused by higher doses of methamphetamine. These results match earlier findings with cocaine, suggesting the iboga agents interact with brain pathways that control hyperactivity from repeated stimulant use. The authors propose this enhancement may partly explain how these agents reduce drug self-administration.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Ibogaine 18-methoxycoronaridine (18-MC) |
| Dose | 40 mg/kg, IP, 19 h earlier (for 18-MC); 0, 0.25, 0.5, 1 and 2 mg/kg, IP (for methamphetamine locomotion); 2 and 4 mg/kg, IP (for methamphetamine stereotypy); 4 mg/kg daily for 7 days (chronic methamphetamine) |
| Keywords | Stimulant misuse methamphetamine Stimulants Drug self-administration Chronic methamphetamine exposure Stimulant-driven hyperactivity |
| Citations | 28 |
| Key finding | Pretreatment with ibogaine or 18-MC enhanced methamphetamine-induced locomotion and stereotypy in rats treated chronically with methamphetamine, consistent with prior cocaine findings. |
Abstract
The phenomenon of sensitization has been theoretically implicated in mediating various aspects of drug addiction. Recent dose-response studies demonstrated that pretreatment with the putative antiaddictive agent, ibogaine (IBO), and a synthetic iboga alkaloid congener, 18-methoxycoronaridine (18-MC), increase the potency of cocaine to elicit behavioral sensitization, an effect proposed to contribute, in part, to their ability to attenuate drug self-administration. As abuse of the methylated amphetamine derivative, methamphetamine (METH), is a growing public health concern, the present study determined the interactions between IBO and 18-MC and the expression of METH-induced behavioral sensitization. The effects of pretreatment with 18-MC (40 mg/kg, IP, 19 h earlier) on the expression of METH-induced locomotion (0, 0.25, 0.5, 1 and 2 mg/kg, IP) and the effects of pretreatment with either IBO or 18-MC on the expression of METH-induced stereotypy (2 and 4 mg/kg, IP) were assessed in rats treated chronically with either METH (4 mg/kg daily for 7 days) or saline. Compared to vehicle-pretreated controls, 18-MC produced an overall enhancement in METH-induced locomotion in rats treated chronically, but not acutely, with METH. In addition, both iboga agents increased the stereotypic response to METH. Iboga agents augment both the locomotor and stereotypic effects of METH in a manner consistent with previous reports for cocaine. Thus, it appears that iboga agents interact in a similar manner with the neural mechanisms mediating motor hyperactivity induced by the chronic administration of stimulant drugs.