Comparative neurobiological effects of ibogaine and MK-801 in rats.
M H Baumann, R B Rothman, S F Ali
Drug and alcohol dependence May 1, 2000 DOI: 10.1016/s0376-8716(99)00113-1 via PubMed
Summary
AI-generated from the abstractIbogaine, a plant alkaloid, reduces dopamine levels across several brain regions in rats while increasing dopamine metabolites, indicating enhanced dopamine turnover. This effect differs from MK-801, an NMDA antagonist, which does not lower dopamine but modestly raises metabolites in some areas. Both drugs elevate corticosterone, but only ibogaine increases prolactin. The findings suggest ibogaine's in vivo actions on dopamine and neuroendocrine secretion are not solely due to NMDA receptor antagonism.
Study at a glance
| Characteristics | Controlled laboratory experiment Peer reviewed |
|---|---|
| Population | Male rats |
| Interventions | Ibogaine MK-801 |
| Dose | 10 and 100 mg/kg ibogaine, 0.1 and 1 mg/kg MK-801 |
| Duration | 30 or 60 min after injection |
| Topics | Ibogaine |
| Keywords | Plant compound Anti-addiction compound Therapeutic compound Neuropharmacology |
| Citations | 15 |
| Key finding | Ibogaine's effects on dopamine metabolism and neuroendocrine secretion are not fully mimicked by MK-801, indicating its actions cannot be explained solely by NMDA receptor antagonism. |
Abstract
Ibogaine is a plant-derived alkaloid with putative 'anti-addictive' properties. Although ibogaine binds to multiple targets in the brain, recent evidence suggests the drug acts as an N-methyl-D-aspartate (NMDA) antagonist similar to MK-801. The purpose of the present study was to compare neurochemical and neuroendocrine effects of ibogaine and MK-801 in vivo. Male rats received either i.p. saline, ibogaine (10 and 100 mg/kg), or MK-801 (0.1 and 1 mg/kg). Groups of rats (N=6-8/group) were decapitated 30 or 60 min after injection. Brains were harvested for analysis of dopamine (DA) and its metabolites, while trunk blood was collected for analysis of plasma corticosterone and prolactin. Ibogaine produced marked dose-dependent reductions in tissue DA with concurrent increases in the metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This profile of ibogaine-induced effects on DA metabolism was consistently observed in the cortex, striatum, olfactory tubercle, and hypothalamus. MK-801, on the other hand, did not reduce DA levels in any brain region but did cause modest region-specific elevations in DA metabolites. Ibogaine and MK-801 caused comparable elevations in circulating corticosterone, but only ibogaine increased prolactin. The present findings show that the effects of ibogaine on DA neurotransmission and neuroendocrine secretion are not fully mimicked by MK-801. Thus, the wide spectrum of in vivo actions of ibogaine can probably not be explained simply on the basis of antagonism at NMDA receptors.