Attenuation of morphine withdrawal signs by intracerebral administration of 18-methoxycoronaridine.
Vishal Panchal, Olga D Taraschenko, Isabelle M Maisonneuve, Stanley D Glick
European journal of pharmacology November 21, 2005 DOI: 10.1016/j.ejphar.2005.09.060 via PubMed
Summary
18-Methoxyroconaridine (18-MC), a synthetic derivative of ibogaine, reduces morphine self-administration and alleviates several signs of acute opioid withdrawal in rats. The mechanism behind 18-MC's attenuation of opioid withdrawal was unknown. In vitro studies show 18-MC is a potent antagonist of alpha3beta4 nicotinic receptors, predominantly located in the medial habenula and interpeduncular nuclei. To test whether brain areas with high densities of these receptors are involved, 18-MC was locally administered into the medial habenula, interpeduncular nucleus, and locus coeruleus of morphine-dependent rats, followed by naltrexone to precipitate withdrawal.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Morphine-dependent rats |
| Keywords | Morphine withdrawal relief Addiction intervention Substance dependence management 18-mc 18-methoxyroconaridine Experimental compound |
| Citations | 30 |
| Key finding | Local administration of 18-MC into the locus coeruleus, medial habenula, and interpeduncular nucleus suppressed various signs of opioid withdrawal in morphine-dependent rats. |
Abstract
18-Methoxyroconaridine (18-MC), a synthetic derivative of ibogaine, reduces morphine self-administration and alleviates several signs of acute opioid withdrawal in rats. Although there is already well documented evidence of the mechanism mediating 18-MC's action to reduce the rewarding effects of morphine, nothing is known about the mechanism responsible for 18-MC's attenuation of opioid withdrawal. In vitro studies have demonstrated that 18-MC is a potent antagonist of alpha3beta4 nicotinic receptors (IC50=0.75 microM), which are predominantly located in the medial habenula and interpeduncular nuclei. Previous work indicating that alpha3beta4 nicotinic receptors mediate 18-MC's effects on drug self-administration prompted us to assess whether brain areas having high or moderate densities of alpha3beta4 receptors might be involved in 18-MC's modulation of opioid withdrawal. To test this possibility, 18-MC was locally administered into the medial habenula, interpeduncular nucleus and locus coeruleus of morphine-dependent rats; this treatment was followed by naltrexone to precipitate a withdrawal syndrome. Pretreatment with various doses of 18-MC into the locus coeruleus significantly reduced wet-dog shakes, teeth chattering, burying and diarrhea, while pretreatment into the medial habenula attenuated teeth chattering, burying, and weight loss. Some doses of 18-MC administered into the interpeduncular nucleus significantly ameliorated rearing, teeth chattering, and burying, while other doses exacerbated diarrhea and teeth chattering. The present findings suggest that 18-MC may act in all three nuclei to suppress various signs of opioid withdrawal.