Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration.
Stanley D Glick, Elizabeth M Sell, Isabelle M Maisonneuve
European Journal of Pharmacology October 1, 2008 DOI: 10.1016/j.ejphar.2008.09.038 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats self-administering methamphetamine or sucrose |
| Interventions | 18-methoxycoronaridine (18-MC) Mecamylamine alpha-conotoxin AuIB |
| Topics | Ibogaine |
| Keywords | Brain Tegmentum mesencephali Amygdala Animals Rats, long-evans Methamphetamine Mecamylamine Sucrose Receptors, nicotinic Nicotinic antagonists Conotoxins Self administration Drug administration routes Behavior, addictive Female |
| Key findings | Local infusion of 18-MC, mecamylamine, or alpha-conotoxin AuIB into the medial habenula, interpeduncular area, or basolateral amygdala decreased methamphetamine self-administration, while infusions into the dorsolateral tegmentum or ventral tegmental area did not. The same antagonists decreased sucrose self-administration when infused into the dorsolateral tegmentum or basolateral amygdala but not the medial habenula, interpeduncular nucleus, or ventral tegmental area. The authors argue that 18-MC reduces methamphetamine self-administration by blocking alpha3beta4 nicotinic receptors in the habenulo-interpeduncular pathway and basolateral amygdala, indirectly modulating the mesolimbic dopamine 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 several drugs of abuse. Previous work has established that 18-MC is a potent antagonist at alpha3beta4 nicotinic receptors. Because high densities of alpha3beta4 nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine self-administration in rats. Local administration of 18-MC into either the medial habenula, the interpeduncular area or the basolateral amygdala decreased methamphetamine self-administration. 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, or the other antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine self-administration. In contrast, local administration of 18-MC and the other antagonists decreased sucrose self-administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area. These data are consistent with the hypothesis that 18-MC decreases methamphetamine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of alpha3beta4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. The data also suggest that the basolateral amygdala along with a different pathway involving alpha3beta4 receptors in the dorsolateral tegmentum mediate the effect of 18-MC on sucrose self-administration.
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 7
- Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration. Addiction Biology October 1, 2010
- Interaction of ibogaine with human alpha3beta4-nicotinic acetylcholine receptors in different conformational states. The international journal of biochemistry & cell biology September 1, 2010
- 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
- Rare but relevant: Ibogaine and cardiovascular complications-prolonged QT interval and ventricular arrhythmias. Addiction January 20, 2026
and 2 more in the library
Cites 9
- 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
- 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
and 4 more in the library