Attenuation of morphine withdrawal signs by intracerebral administration of 18-methoxycoronaridine

Vishal Panchal, Olga D. Taraschenko, Isabelle M. Maisonneuve, Stanley D. Glick

Research output: Contribution to journalArticle

24 Scopus citations

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 α3β4 nicotinic receptors (IC 50 = 0.75 μM), which are predominantly located in the medial habenula and interpeduncular nuclei. Previous work indicating that α3β4 nicotinic receptors mediate 18-MC's effects on drug self-administration prompted us to assess whether brain areas having high or moderate densities of α3β4 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.

Original languageEnglish (US)
Pages (from-to)98-104
Number of pages7
JournalEuropean Journal of Pharmacology
Volume525
Issue number1-3
DOIs
StatePublished - Nov 21 2005

Keywords

  • Interpeduncular nucleus
  • Locus coeruleus
  • Medial habenula
  • Morphine
  • Naltrexone
  • Physical dependence

ASJC Scopus subject areas

  • Pharmacology

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