Neurochemical and Neuroendocrine Effects of Ibogaine in Rats: Comparison to MK-801.
Michael H. Baumann, Richard B. Rothman, Syed F. Ali
Annals of the New York Academy of Sciences May 1, 1998 DOI: 10.1111/j.1749-6632.1998.tb08240.x via PubMed
Summary
AI-generated from the abstractIbogaine, a natural compound being studied for substance use disorders, was compared to the NMDA antagonist MK-801 in male rats to understand its mechanism of action. Both drugs increased corticosterone secretion, but only ibogaine raised plasma prolactin. Ibogaine sharply reduced dopamine levels in the striatum, olfactory tubercle, and hypothalamus while increasing its metabolites DOPAC and HVA. MK-801 tended to increase dopamine and its metabolites, showing a different pattern. Neither drug affected serotonin systems. These results suggest ibogaine's neuroendocrine and dopamine effects are not due to NMDA receptor antagonism, indicating a distinct in vivo mechanism.
Study at a glance
| Characteristics | Preclinical drug study Peer reviewed |
|---|---|
| Population | Male rats |
| Interventions | Ibogaine MK-801 |
| Dose | 10 & 100 mg/kg ibogaine; 0.1 & 1.0 mg/kg MK-801 |
| Duration | 30 and 60 minutes after injection |
| Topics | Ibogaine |
| Keywords | Ibogaine: natural compound Ibogaine's effects Its action Mechanism Neuroendocrine function |
| Citations | 11 |
| Key finding | Ibogaine's effects on neuroendocrine function and dopamine transmission in rats differ from MK-801, indicating its in vivo mechanism is not simply NMDA receptor antagonism. |
Abstract
Ibogaine (IBO) is a naturally-occurring indole compound that is being evaluated as a potential medication for substance use disorders. Although the precise mechanism of IBO action is unclear, recent in vitro data show this drug displays properties similar to the noncompetitive N-methyl-d-aspartate (NMDA) antagonist MK-801. The purpose of the present work was to compare In Vivo neurobiological effects of IBO and MK-801 in rats. Groups of male rats (n = 6-8/group) were decapitated 30 and 60 min after receiving intraperitoneal (i.p.) IBO (10 & 100 mg/kg), MK-801 (0.1 & 1.0 mg/kg) or vehicle. Trunk blood was collected for the analysis of plasma prolactin and corticosterone; brains were harvested and dissected for determination of dopamine (DA), serotonin (5-HT) and their metabolites. Both IBO and MK-801 increased corticosterone secretion, but only IBO elevated plasma prolactin. IBO produced dramatic reductions in tissue DA levels with concurrent increases in the metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This profile of IBO-induced changes in DA transmission was observed in the striatum, olfactory tubercle, and hypothalamus. The effects of MK-801 on DA metabolism did not mimic IBO, as MK-801 tended to increase DA and its metabolites. Neither drug appreciably affected 5-HT systems. Our results suggest that the effects of IBO on neuroendocrine function and DA transmission are not due to MK-801-like properties of IBO. Thus, the In Vivo mechanism of IBO action cannot be explained simply on the basis of antagonism at NMDA receptors.