Ibogaine (IBO) is a psychoactive indole alkaloid that has antiaddictive properties. However, treatment with IBO may lead to neurotoxicity, since IBO and its metabolites interact persistently with many neurotransmitter systems. Here, we recorded cortical electroencephalogram (EEG) signals from rats anesthetized with isoflurane. The heart rate (HR) was monitored via electrocardiogram (EKG)...
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...
The structural features and hallucinogenic properties shared by ibogaine and certain beta-carbolines prompted the evaluation of several representative beta-carbolines in rats trained with ibogaine as a discriminative stimulus. In a previous report from our laboratory harmaline completely substituted for ibogaine (83.5%). In the present study, only 6-methoxyharmalan completely substituted...
The discriminative stimulus properties of ibogaine were investigated in rats trained to discriminate phencyclidine (PCP; 2.0 mg/kg, I.P.) from saline under a two-lever fixed-ratio (FR) 32 schedule of food reinforcement. Ibogaine (5.6-17.6 mg/kg, I.P.) showed a complete lack of substitution. Ibogaine (0.5-4.0 mg/kg, I.M.) also failed to generalize in rhesus monkeys trained to discriminate PCP...
In the present investigation, the ability of two known hallucinogens, lysergic acid dimethylamide (LSD) and (-)-2,5-dimethoxy-4-methyl-amphetamine (DOM), to substitute for the ibogaine-induced discriminative stimulus (10 mg/kg I.P., 60 min presession) was assessed in Fischer-344 rats. In these subjects, intermediate levels of generalization were observed to both agents (LSD, 63%; DOM, 66.4%)....
Although the mechanism of action of ibogaine, a hallucinogen that may be useful in the treatment of addiction, remains unknown, receptor binding studies suggest that ibogaine produces its effects via interactions with multiple receptor types. In addition to serotonergic receptors, which have been studied previously with respect to ibogaine, likely candidates include opiate, sigma (sigma), and...
Noribogaine is formed in vivo by the O-demethylation of the indole alkaloid ibogaine. We report here that noribogaine acts as a full agonist at the mu-opioid receptor. Noribogaine-stimulated guanylyl 5'gamma-[35S]thio]triphosphate ([35S]GTPgammaS) was studied in rat thalamic membranes to measure activation of guanine nucleotide binding proteins (G-proteins) in the presence of excess GDP....
The neural basis of ibogaine's effects on drug-related behaviours is unclear. One possibility is that ibogaine interferes with the shared capacity of many addictive agents to stimulate brain dopamine activity, but reports of ibogaine effects on dopamine activity have been inconsistent. Our study suggests such inconsistencies may result from variations in prior drug exposure. If ibogaine blocks...
Ibogaine, an indole alkaloid that causes hallucinations, tremor, and ataxia, produces cerebellar neurotoxicity in rats, manifested by degeneration of Purkinje cells aligned in narrow parasagittal bands that are coextensive with activated glial cells. Harmaline, a closely related alkaloid that excites inferior olivary neurons, causes the same pattern of Purkinje cell degeneration, providing a...
The effects of noribogaine, a metabolite of ibogaine, on the development of tolerance to the antinociception action of morphine was determined in male Swiss-Webster mice. Ibogaine is an alkaloid isolated from the bark of the African shrub, Tabernanthe iboga. Morphine tolerance in mice was developed by two different methods. Mice were rendered tolerant to morphine either by subcutaneous...