Ibogaine effects on sweet preference and amphetamine induced locomotion: implications for drug addiction (original) (raw)
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Differential effects of ibogaine on behavioural and dopamine sensitization to cocaine
European Journal of Pharmacology, 2000
To investigate a possible basis for the proposed anti-addictive property of ibogaine, the effects of ibogaine 40 mgrkg, i.p., 19 h. earlier on the expression of sensitization induced by cocaine were investigated. Ibogaine pretreatment potentiated the increase in the Ž. Ž. stereotypic effects of a cocaine challenge 20 mgrkg in both sensitized 5 = 15 mgrkg, i.p. and acutely treated rats. However, while ibogaine pretreatment did not significantly alter the dopamine response in the nucleus accumbens to acute cocaine, it abolished the expression of cocaine-induced dopamine sensitization. This result demonstrates that ibogaine pretreatment can reverse one of the neuroadaptations produced by chronic cocaine administration, an effect that may contribute to its putative anti-addictive property.
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.
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);
Brain Research, 1992
lbogaine, an indolalkylamine. proposed for use in treating opiate and stimulant addiction, has been shown to modulate the dopaminergic iystem acutely and one day later. In the present study we sought to systematically determine the effects of ibogaine on the levels of dopanine (DA) and the dopamine metabolites 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in tissue at several time Joints, between 1 h and 1 month post-injection. One hour after ibogaine-administration (40 m@g i.p.) a 50% decrease in DA along with a 17-100% increase in HVA were observed in all 3 brain regions studied: striatum, nucleus accumbens and prefrontal cortex. Nineteen hours tfter ibogaine-administration a decrease in DOPAC was seen in the nucleus accumbens and in the striatum. A week after administration of bogaine striatal DOPAC levels were still reduced. A month after ibogaine injection there were no significant neurochemical changes in any Legion. We also investigated the effects of ibogaine pretreatment on morphine-induced locomotor activity, which is thought to depend on DA release. Using photocell activity cages we found that ibogaine pretreatment decreased the stimulatory motor effects induced by a wide rnge of morphine doses (OS-20 mgkg. i.p.) administered 19 h later; a similar effect was observed when morphine (5 m&g) was adminstered a week after ibogaine pretreatment. No significant changes in morphine-induced locomotion were seen a month after ibogaine pre-:reatment. The present findings indicate that ibogaihe produces both acute and delayed effects on the tissue content of DA and its metabelites, and these changes coincide with a sustained depression of morphine-induced locomotor activity.
Frontiers in Pharmacology, 2021
Ibogaine is a psychedelic extracted from the plant Tabernanthe iboga Baill. (Apocynaceae), natural from Africa, and has been proposed as a potential treatment for substance use disorders. In animal models, ibogaine reduces ethanol self-administration. However, no study to date has investigated the effects of ibogaine on ethanol-induced conditioned place preference (CPP). The present study aimed to investigate the effects of repeated treatment with ibogaine on the reinstatement of CPP to ethanol in male mice. The rewarding effects of ethanol (1.8 g/kg, i. p.) or ibogaine (10 or 30 mg/kg, p. o.) were investigated using the CPP model. Furthermore, we evaluated the effects of repeated treatment with ibogaine (10 or 30 mg/kg, p. o.) on the reinstatement of ethanol-induced CPP. Reinstatement was evaluated under two conditions: 1) during a priming injection re-exposure test in which animals received a priming injection of ethanol and had free access to the CPP apparatus; 2) during a drug-f...
Psychopharmacology, 1999
Rationale: Results of single-dose studies suggest that the effects of pretreatment with the putative anti-addictive compound, ibogaine, on drug-induced locomotor behavior depends on the previous drug history of the animal. Objectives: To compare the effects of ibogaine pretreatment on the dose-locomotor response function for cocaine in rats treated chronically with either saline or cocaine. Methods: Rats were chronically treated with either cocaine (15 mg/kg, IP, once daily for 5 days, followed by 2 week withdrawal) or saline. Ibogaine (40 mg/kg, IP) or vehicle was administered and 19 h later, a cocaine dose-locomotor response test was conducted (0, 5, 10, 20 and 40 mg/kg, IP). Results: Chronic cocaine administration augmented the locomotor response to cocaine in chronic cocaine-treated rats, compared to acutely treated controls. Ibogaine pretreatment enhanced the locomotor effects of cocaine in both chronic and acute cocaine groups. Furthermore, due to the shape of the dose-response curve, in chronic cocaine but not in acute cocaine rats, ibogaine pretreatment enhanced the locomotor response to 5 and 10 mg/kg cocaine while decreasing the locomotor response to 40 mg/kg cocaine. Conclusions: These data demonstrate definitively that ibogaine can enhance sensitivity to the locomotor stimulant effects of cocaine, an effect which depends, in part, on the previous cocaine history of the animal.
Psychopharmacology, 1996
The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. Ibogaine undergoes first pass metabolism and isO-demethylated to 12-hydroxyibogamine (12-OH ibogamine). Radioligand binding assays were conducted to identify the potency and selectivity profiles for ibogaine and 12-OH ibogamine. A comparison of 12-OH ibogamine to the primary molecular targets identified previously for ibogaine demonstrates that the metabolite has a binding profile that is similar, but not identical to the parent drug. Both ibogaine and 12-OH ibogamine demonstrated the highest potency values at the cocaine recognition site on the 5-HT transporter. The same rank order (12-OH ibogamine > ibogaine), but lower potencies were observed for the [3H]paroxetine binding sites on the 5-HT transporter. Ibogaine and 12-OH ibogamine were equipotent at vesicular monoamine and dopamine transporters. The metabolite demonstrated higher affinity at the kappa-1 receptor and lower affinity at the NMDA receptor complex compared to the parent drug. Quantitation of the regional brain levels of ibogaine and 12-OH ibogamine demonstrated micromolar concentrations of both the parent drug and metabolite in rat brain. Drug dependence results from distinct, but inter-related neurochemical adaptations, which underlie tolerance, sensitization and withdrawal. Ibogaine’s ability to alter drug-seeking behavior may be due to combined actions of the parent drug and metabolite at key pharmacological targets that modulate the activity of drug reward circuits.