18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine self-administration in rats.
Stanley D Glick, Ruby L Ramirez, Jacklyn M Livi, Isabelle M Maisonneuve
European Journal of Pharmacology March 24, 2006 DOI: 10.1016/j.ejphar.2006.03.045 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study in rats Peer reviewed |
|---|---|
| Population | Rats self-administering morphine or sucrose |
| Interventions | 18-methoxycoronaridine (18-MC) Mecamylamine alpha-conotoxin AuIB |
| Topics | Ibogaine |
| Keywords | Mesencephalon Habenula Animals Rats, long-evans Morphine dependence Mecamylamine Sucrose Receptors, nicotinic Nicotinic antagonists Narcotics Conotoxins Self administration Behavior, addictive Female |
| Key findings | Local administration of 18-MC into the medial habenula or interpeduncular area decreased morphine self-administration without affecting sucrose responding, as did the alpha3beta4 nicotinic antagonists mecamylamine and alpha-conotoxin AuIB; injections into the ventral tegmental area had no effect. The authors argue these data support the hypothesis that 18-MC reduces morphine self-administration by blocking alpha3beta4 nicotinic receptors in the habenulo-interpeduncular pathway. |
Abstract
The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the self-administration of morphine and other drugs of abuse. Previous work has established that 18-MC is a potent antagonist at alpha3beta4 nicotinic receptors. Because alpha3beta4 nicotinic receptors in the brain are preferentially located in the medial habenula and the interpeduncular nucleus, the present study was conducted to determine if 18-MC could act in these brain areas to modulate morphine self-administration in rats. Local administration of 18-MC into either the medial habenula or the interpeduncular area decreased morphine self-administration while having no effect on responding for a non-drug reinforcer (sucrose). Similar results were produced by local administration into the same brain areas of two other alpha3beta4 nicotinic antagonists, mecamylamine and alpha-conotoxin AuIB. Local administration of 18-MC into the ventral tegmental area had no effect on morphine self-administration. These and other data are consistent with the hypothesis that 18-MC decreases morphine self-administration by blocking alpha3beta4 nicotinic receptors in the habenulo-interpeduncular pathway.
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 13
- Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration. Addiction Biology October 1, 2010
- The Iboga Alkaloids. Progress in the chemistry of organic natural products 2017
- Acute oral 18-methoxycoronaridine (18-MC) decreases both alcohol intake and IV nicotine self-administration in rats. Pharmacology, Biochemistry, and Behavior 2016
- What We Have Gained from Ibogaine: α3β4 Nicotinic Acetylcholine Receptor Inhibitors as Treatments for Substance Use Disorders. Journal of Medicinal Chemistry January 12, 2023
- Structure-activity relationship of ibogaine analogs interacting with nicotinic acetylcholine receptors in different conformational states. The international journal of biochemistry & cell biology September 1, 2011
and 8 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
- 18-Methoxycoronaridine (18-MC) and ibogaine: comparison of antiaddictive efficacy, toxicity, and mechanisms of action. Annals of the New York Academy of Sciences September 1, 2000
- Attenuation of alcohol consumption by a novel nontoxic ibogaine analogue (18-methoxycoronaridine) in alcohol-preferring rats. Pharmacology, Biochemistry, and Behavior October 1, 1997
- Development of novel medications for drug addiction. The legacy of an African shrub. Annals of the New York Academy of Sciences 2000
and 1 more in the library