18-MC acts in the medial habenula and interpeduncular nucleus to attenuate dopamine sensitization to morphine in the nucleus accumbens.
Olga D Taraschenko, Joseph M Shulan, Isabelle M Maisonneuve, Stanley D Glick
Synapse July 1, 2007 DOI: 10.1002/syn.20396 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | 18-Methoxycoronaridine (18-MC) Morphine |
| Dose | 10 mug |
| Topics | Ibogaine |
| Keywords | Mesencephalon Nucleus accumbens Animals Rats, sprague-dawley Dopamine 3,4-dihydroxyphenylacetic acid Homovanillic acid Morphine Narcotics Drug administration routes Drug administration schedule Analysis of variance Dose-response relationship, drug Drug interactions Time factors Female |
| Key findings | Local infusion of 10 micrograms of 18-MC into either the interpeduncular nucleus or the medial habenula blocked the sensitized dopamine response to repeated morphine in the nucleus accumbens, but had no effect on the dopamine response to acute morphine. The authors suggest 18-MC acts in the habenulo-interpeduncular pathway to modulate the effects of repeated morphine on the mesolimbic dopamine system. |
Abstract
18-Methoxycoronaridine (18-MC), a novel iboga alkaloid congener, is a potential treatment for drug addiction. 18-MC has been shown to decrease self-administration of drugs (e.g., morphine, methamphetamine, nicotine) and attenuate opioid withdrawal in rats. In previous studies, systemic pretreatment with 18-MC abolished the sensitized increase in accumbens dopamine levels induced by chronic morphine administration. In vitro studies have shown that 18-MC is a potent antagonist of alpha3beta4 nicotinic receptors, and alpha3beta4 antagonism is believed to be the primary mechanism responsible for 18-MC's effects on drug self-administration and possibly on morphine-induced changes in mesolimbic dopamine. While there are very low densities of alpha3beta4 nicotinic receptors in the mesolimbic pathway, these receptors are prominently localized in the medial habenula (MHb) and in the interpeduncular nucleus (IPN). These nuclei and the habenulo-interpeduncular pathway connecting them are believed to function as part of an alternate reward pathway modulating the dopaminergic mesolimbic pathway known to be involved in drug addiction. In the present study, to determine if 18-MC acts in the MHb or in the IPN, the effects of local infusion of 18-MC into these brain areas were assessed on mesolimbic dopamine responses to acute and repeated morphine treatment. Administration of 18-MC (10 mug) into either the IPN or MHb blocked the sensitized dopamine response to repeated morphine in the nucleus accumbens; 18-MC had no effect on the dopamine response to acute morphine. The results suggest that 18-MC acts in the habenulo-interpeduncular pathway to modulate the effects of repeated morphine in the dopaminergic mesolimbic system.
Comparable studies
Other preclinical and animal studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine TE671/RD cells (human muscle-type nAChR) and SH-SY5Y neuroblastoma cells (human... | 1999 | In vitro study | |
| Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Ibogaine- or harmaline-treated rats | 1993 | Experimental animal study | |
| Effects and aftereffects of ibogaine on morphine self-administration in rats. Rats | 1991 | Preclinical experimental study | |
| Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Rats | 1994 | Experimental study | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study |
Citations in the library
Cited by 6
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- The ibogaine medical subculture. Journal of Ethnopharmacology January 4, 2008
- Serotonergic hallucinogens and emerging targets for addiction pharmacotherapies. Psychiatric Clinics of North America June 1, 2012
- Acute oral 18-methoxycoronaridine (18-MC) decreases both alcohol intake and IV nicotine self-administration in rats. Pharmacology, Biochemistry, and Behavior 2016
- Ibogaine: Therapeutic Potential, Cardiac Safety, and Translational Perspectives in the Treatment of Substance Use Disorders—A Scoping Review Molecules February 4, 2026
and 1 more in the library
Cites 6
- Antagonism of alpha 3 beta 4 nicotinic receptors as a strategy to reduce opioid and stimulant self-administration. European Journal of Pharmacology March 1, 2002
- 18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats. Brain Research May 6, 1996
- Anti-addictive actions of an iboga alkaloid congener: a novel mechanism for a novel treatment. Pharmacology, Biochemistry, and Behavior June 1, 2003
- Effects of 18-methoxycoronaridine on acute signs of morphine withdrawal in rats. Neuroreport May 11, 1998
- 18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine self-administration in rats. European Journal of Pharmacology March 24, 2006
and 1 more in the library