ScienceDirect - The Alkaloids: Chemistry and Biology : Chapter 10 Ibogaine neurotoxicity assessment: Electrophysiological, neurochemical, and neurohistological methods

The Alkaloids: Chemistry and Biology
Volume 56, 2001, Pages 193-210

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Ibogaine Enhances the Expression of Locomotor Sensitization in Rats Chronically Treated With Cocaine
Pharmacology Biochemistry and Behavior, Volume 63, Issue 3, July 1999, Pages 457-464
Karen K. Szumlinski, Isabelle M. Maisonneuve, Stanley D. Glick

Abstract

Pretreatment (19 h) with the putative antiaddictive agent, ibogaine, has been shown previously to potentiate cocaine-induced locomotion in rats. The present study demonstrates that the magnitude of this effect of ibogaine is dependent on the previous cocaine history of the animal, on the time following ibogaine treatment, and on the number of ibogaine treatments. Compared to rats with no previous cocaine experience, ibogaine pretreatment (40 mg/kg, IP, 19 h earlier) markedly enhanced the expression of locomotor sensitization in response to a cocaine challenge injection (7.5 mg/kg) in rats that were chronically treated with cocaine (15 mg/kg, IP, daily for 5 days). Tolerance to cocaine-induced locomotor sensitization appeared to occur in vehicle-pretreated chronic cocaine controls. Following a second series of identical treatments (beginning 3–4 days after the initial treatment series), locomotor responding to the cocaine challenge was further enhanced by a second ibogaine injection in chronically cocaine-treated animals. Twenty-four hours later, when animals were challenged again with cocaine in the absence of any further ibogaine pretreatment, the effect of ibogaine had dissipated. Consistent with previous studies from this laboratory, these data demonstrate that ibogaine can enhance sensitivity to the psychomotor stimulant effect of cocaine. The results of the present study further indicate that the extent of this effect depends on the animal’s history of exposure to both ibogaine and cocaine.

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Interactions between ibogaine and cocaine in rats: in v...
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Interactions between ibogaine and cocaine in rats: in vivo microdialysis and motor behavior
European Journal of Pharmacology, Volume 212, Issues 2-3, 3 March 1992, Pages 263-266
I.M. Maisonneuve, S.D. Glick

Abstract

To investigate a possible basis for the proposed anti-addictive property of ibogaine, the effects of an ibogaine (40 mg/kg i.p.) pretreatment on in vivo neurochemical and motor effects induced by cocaine (20 mg/kg i.p.) were studied. Ibogaine, administered 19 h earlier, potentiated the increase in extracellular dopamine levels in striatum and nucleus accumbens as well as the stimulated motor activity induced by cocaine. Although high doses of cocaine can become aversive by producing an anxiogenic reaction, it is unknown whether the potentiation of cocaine's effects by ibogaine would also cause aversion and lead to a decrease in cocaine addiction.

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Differential effects of ibogaine on behavioural and dop...
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Differential effects of ibogaine on behavioural and dopamine sensitization to cocaine
European Journal of Pharmacology, Volume 398, Issue 2, 16 June 2000, Pages 259-262
Karen K. Szumlinski, Isabelle M. Maisonneuve, Stanley D. Glick

Abstract

To investigate a possible basis for the proposed anti-addictive property of ibogaine, the effects of ibogaine (40 mg/kg, i.p., 19 h earlier) on the expression of sensitization induced by cocaine were investigated. Ibogaine pretreatment potentiated the increase in the stereotypic effects of a cocaine challenge (20 mg/kg) in both sensitized (5×15 mg/kg, 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.

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Ibogaine pretreatment dramatically enhances the dynorph...
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Ibogaine pretreatment dramatically enhances the dynorphin response to cocaine
Brain Research, Volume 847, Issue 1, 13 November 1999, Pages 139-142
Mario E. Alburges, Glen R. Hanson

Abstract

Ibogaine (Endabuse™) is a psychoactive indole alkaloid found in the shrub, Tabernanthe iboga, which has been used to treat stimulant addiction. Because ibogaine influences the activity of neurotensin systems, a dopamine-linked neuropeptide, the present study investigated if ibogaine also influences dynorphin (DYN) pathways. Unlike neurotensin responses, ibogaine alone did not alter DYN levels in the striatum, substantia nigra or nucleus accumbens. Interestingly, ibogaine pretreatment dramatically enhanced cocaine-induced increases in DYN content in these structures.

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Ibogaine modulates cocaine responses which are altered ...
Pharmacology Biochemistry and Behavior

Ibogaine modulates cocaine responses which are altered due to environmental habituation: In vivo microvoltammetric and behavioral studies
Pharmacology Biochemistry and Behavior, Volume 49, Issue 3, November 1994, Pages 711-728
Patricia A. Broderick, Frank T. Phelan, Frank Eng, Robert T. Wechsler

Abstract

Ibogaine, a serotonergic (5-HTergic) indole alkaloid, was studied for cocaine modulatory effects on four parameters of behavior by computerized infrared photocell beam detection. The behavioral parameters were: a) locomotor activity (ambulations), b) rearing, c) stereotypy (fine movements, primarily grooming), and d) agoraphobia [(thigmotaxis) a natural tendency to avoid the center of the behavioral chamber]. With each behavioral data point, dopamine (DA) release, and serotonin (5-HT) release were detected within seconds in nucleus accumbens (NAcc) of the same behaving male Sprague-Dawley rats, using in vivo electrochemistry (voltammetry). Ibogaine was administered (40 mg/kg IP) for 4 consecutive days. Importantly, the DAergic and the 5-HTergic responses to (SC) cocaine and two behavioral responses, ambulations and central ambulations, were reduced in intensity due to extended time spent in the novel behavioral chamber (habituated). Rearing and fine movement patterns were not habituated. The results show that ibogaine downmodulated the (SC) cocaine-induced increase in NAcc DA release (p < 0.0001) and potentiated the (SC) cocaine-induced decrease in NAcc 5-HT release (p < 0.0001). Concurrently, ibogaine downmodulated cocaine-induced ambulation (p < 0.0001) and central ambulation behavior (p < 0.0001). On the other hand, the behavioral parameters that did not exhibit habituation, i.e., rearing behavior and fine movement behavior, were not downmodulated by ibogaine (p < 0.1558) (p < 0.3763), respectively. Furthermore, ibogaine itself did not significantly alter NAcc DA release over the 2-h period studied (p < 0.9113) although individual time points were significantly affected bidirectionally. Concurrently ibogaine significantly increased 5-HT release (p < 0.0155). Behaviorally, ibogaine appears to be a weak psychostimulant. The data show a critical modulatory role for 5-HT in ibogaine-cocaine interactions. Also elucidated as critical is the efficacy of ibogaine when the response to (SC) cocaine is decreased due to the habituation of the animals to their environment.

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