Ibogaine attenuation of morphine withdrawal in mice: role of glutamate N-methyl-D-aspartate receptors.
Mirna Bainy Leal, Kátia Michelin, Diogo Onofre Souza, Elaine Elisabetsky
Progress in neuro-psychopharmacology & biological psychiatry August 1, 2003 DOI: 10.1016/s0278-5846(03)00109-x (opens in new tab) via PubMed
Summary
AI-generated from the abstractIbogaine, a noncompetitive NMDA receptor antagonist, inhibits the behavioral signs of morphine withdrawal in mice. Jumping, a key withdrawal behavior, was reduced by 64.2% and 96.9% with 40 and 80 mg/kg of ibogaine, respectively, and by 67.3% and 97.7% with the NMDA antagonist MK-801. Combining lower doses of both drugs produced a 94.7% inhibition, similar to higher doses of either alone. Ibogaine and MK-801 also blocked NMDA-induced jumping when given 30 minutes before, but not 24 hours before, in non-addicted mice. No changes in NMDA receptor binding were observed across treatment groups, suggesting a functional, transient alteration of NMDA receptors underlies ibogaine's effect on withdrawal.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Morphine-dependent and non-addicted mice |
| Interventions | Ibogaine MK-801 naloxone NMDA |
| Dose | 40 mg/kg, 80 mg/kg, 0.15 mg/kg, 0.30 mg/kg |
| Topics | Ibogaine |
| Keywords | Psychoactive alkaloid Morphine withdrawal Opioid withdrawal Opiate withdrawal |
| Citations | 50 |
| Key finding | Ibogaine inhibits morphine withdrawal symptoms in mice through a functional and transitory alteration of NMDA receptors. |
Abstract
Ibogaine (IBO) is an alkaloid with putative antiaddictive properties, alleviating opiates dependence and withdrawal. The glutamate N-methyl-D-aspartate (NMDA) receptors have been implicated in the physiological basis of drug addiction; accordingly, IBO acts as a noncompetitive NMDA antagonist. The purpose of this study was to evaluate the effects of IBO on naloxone-induced withdrawal syndrome in morphine-dependent mice, focusing on the role of NMDA receptors. Jumping, a major behavioral expression of such withdrawal, was significantly (P<.01) inhibited by IBO (40 and 80 mg/kg, 64.2% and 96.9% inhibition, respectively) and MK-801 (0.15 and 0.30 mg/kg, 67.3% and 97.7%, respectively) given prior to naloxone. Coadministration of the lower doses of IBO (40 mg/kg) and MK-801 (0.15 mg/kg) results in 94.7% inhibition of jumping, comparable to the effects of higher doses of either IBO or MK-801. IBO and MK-801 also significantly inhibited NMDA-induced (99.0% and 71.0%, respectively) jumping when given 30 min (but not 24 h) prior to NMDA in nonaddictive mice. There were no significant differences in [3H]MK-801 binding to cortical membranes from naive animals, morphine-dependent animals, or morphine-dependent animals treated with IBO or MK-801. This study provides further evidence that IBO does have an inhibitory effect on opiate withdrawal symptoms and suggests that the complex process resulting in morphine withdrawal includes an IBO-sensitive functional and transitory alteration of NMDA receptor.