Acute and prolonged effects of ibogaine on brain dopamine metabolism and morphine-induced locomotor activity in rats (original) (raw)
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Effects and aftereffects of ibogaine on morphine self-administration in rats
European Journal of Pharmacology, 1991
lbogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addiction to opiate and stimulant drugs. As I preclini~al test of this claim, the present study sought to determine if ibogaine would reduce the intravenous self-administr~ltion If morphine in rats. Ibogaine dose dependently (2.5-80 mg/kg) decreased morphine intake in the hour after ibogaine treatment acute effect) and, to a lesser extent, a day later (aftereffect);
Neuropharmacological characterization of local ibogaine effects on dopamine release
Journal of Neural Transmission, 1996
Local perfusion with ibogaine (10-6M-10-3M) via microdialysis probes in the nucleus accumbens or striatum of rats produced a biphasic dose-response effect on extracellular dopamine levels. Lower doses (10-6M -10-4M) produced a decrease while higher doses (5 • 10-4M-10-3M) produced an increase in dopamine levels. Dihydroxyphenylacetic acid (DOPAC) levels were not effected. Naloxone (10-6M) and norbinaltorphimine (10-6M -10-SM) did not affect dopamine levels, but when co-administered with ibogaine (10-4M) blocked the decrease in dopamine levels produced by ibogaine. Ibogaine (10-3M) stimulation of dopamine levels in the striatum was calcium independent and not blocked by tetrodotoxin (10 5M). Pretreatment with cocaine (15mg/kg), reserpine (5mg/kg) or alpha-methyl-paratyrosine (250mg/kg) given intraperitoneally significantly reduced ibogaine (10-3M) stimulation of striatal dopamine levels. In striatal synaptosomes, both ibogaine and harmaline (10-7-10-4M) produced dose-dependent inhibition of [3H]-dopamine uptake. These findings suggest that ibogaine has both inhibitory and stimulatory effects on dopamine release at the level of the nerve terminal. It is suggested that the inhibitory effect is mediated by kappa opiate receptors while the stimulatory effect is mediated by interaction with the dopamine uptake transporter.
Brain Research, 1996
Ibogaine, a naturally occurring iboga alkaloid, has been claimed to be effective in treating addiction to opioids and stimulants, and has been reported to inhibit morphine and cocaine self-administration in rats. However, ibogaine also has acute nonspecific side effects (e.g. tremors, decreased motivated behavior in general) as well as neurotoxic effects (Purkinje cell loss) manifested in the vermis of the cerebellum. 18-Methoxycoronaridine (MC) is a novel, synthetic iboga alkaloid congener that mimics ibogaine's effects on drug self-administration without appearing to have ibogaine's other adverse effects. Acutely, in rats, MC decreased morphine and cocaine self-administration but did not affect bar-press responding for water. In some rats, treatment with MC (40 mg/kg) induced prolonged decreases in morphine or cocaine intake lasting several days or weeks. MC had no apparent tremorigenic effect, and there was no evidence of cerebellar toxicity after a high dose (100 mg/kg) of MC. Similar to the effects of ibogaine and other iboga alkaloids that inhibit drug self-administration, MC (40 mg/kg) decreased extracellular levels of dopamine in the nucleus accumbens. MC therefore appears to be a safer, ibogaine-like agent that might be useful in the treatment of addictive disorders.
Ibogaine attenuation of morphine withdrawal in mice: role of glutamate N-methyl--aspartate receptors
Progress in Neuro- …, 2003
Ibogaine (IBO) is an alkaloid with putative antiaddictive properties, alleviating opiates dependence and withdrawal. The glutamate Nmethyl-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 [ 3 H]MK-801 binding to cortical membranes from naive animals, morphinedependent 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 IBOsensitive functional and transitory alteration of NMDA receptor.
IBOGAINE is a potentially hallucinogenic indole alkaloid with anecdotal antiaddictive properties against multiple drugs of abuse. Medical literature concerning the administration of this substance to humans is sparce. Ibogaine HCL (20-25 mg/kg) was administered orally to five subjects addicted to cocaine and/or opiates. Subjects underwent continuous intensive medical, neurologic and electroencephalographic observation. Movement-induced nausea and vomiting was seen in several subjects, all developed transient ataxia, and several experienced visual hallucinosis. No general medical, EKG or EEG abnormalities were seen. No subjects experienced withdrawal symptoms 24 hours after treatment, and two subjects were free of withdrawal or craving one week after treatment.
Application of Electrophysiological Method to Study Interactions between Ibogaine and Cocaine
Annals of the New York Academy of Sciences, 2006
The psychoactive indole alkaloid, ibogaine (IBO), has been investigated for over a decade concerning its reported anti-addictive properties for opioids as well as psychomotor stimulants. The mechanism for the anti-addictive action of IBO is still unclear. IBO interactions with opioid, NMDA, nicotinic, adrenergic, and serotonergic receptor sites have been suggested. The involvement of the dopaminergic system in IBO action is well documented. Increased or decreased levels of dopamine (DA) in specific brain regions following IBO pretreatment have been seen concomitantly with increased or decreased motor activity after subsequent amphetamine or cocaine administration. In this report, in vivo electrophysiological measures were monitored in awake adult male rats in order to investigate alterations of the electrocorticogram (ECoG) resulting from interactions between IBO and cocaine (COC). Rats were implanted bilaterally with bipolar ECoG electrodes. They were either injected with saline, COC alone (20 mg/kg, i.p.) or IBO (50 mg/kg, i.p.) and COC 1 hr later. The concentrations of DA, 5-HT, and their metabolites DOPAC, HVA, and 5-HIAA were assessed in the caudate nucleus in separate groups of saline-, COC-, and IBO/COC-treated rats. An alpha 1 power increase was observed within 10 min after COC injection, which lasted for less than 20 min. A desynchronization over alpha 2 and both beta power bands was observed throughout the recording. In IBO/COC-treated rats, a significant increase in delta, theta, and alpha 1 power occurred within 20 min after COC injection ( p <0.05). This effect lasted for up to an hour. DA levels significantly increased after COC only and decreased after IBO administration. A further decrease in levels of DA was observed in IBO/COC-treated rats. DA turnover increased significantly after IBO alone but was not observed after IBO/COC treatment. The alterations in ECoG and neurotransmitter levels suggest a decreased response to COC following IBO pretreatment.