Neurochemical and Neuroendocrine Effects of Ibogaine in Rats: Comparison to MK-801.
Annals of the New York Academy of Sciences – May 01, 1998
Source: PubMed
Summary
A natural compound explored for `substance use disorders` shows a unique biological profile. Researchers compared ibogaine's effects on rats to a known drug, MK-801, to uncover its mechanism. They measured `neuroendocrine function`, including `plasma prolactin` and `corticosterone`, alongside brain `dopamine` levels. Ibogaine uniquely elevated `plasma prolactin` and significantly altered `dopamine`, a distinct pattern from MK-801, which also raised `corticosterone`. This demonstrates ibogaine's action isn't simply via the same pathway as MK-801, suggesting a novel approach for `substance use disorders`.
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.