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Related Experiment Videos

18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine

Stanley D Glick1, Ruby L Ramirez, Jacklyn M Livi

  • 1Center for Neuropharmacology and Neuroscience Albany Medical College, MC-136, 47 New Scotland Avenue, NY 12208, USA. glicks@mail.amc.edu

European Journal of Pharmacology
|April 22, 2006
PubMed
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The novel anti-addiction compound 18-methoxycoronaridine (18-MC) reduces morphine intake in rats. This effect is mediated by blocking alpha3beta4 nicotinic receptors in the habenulo-interpeduncular pathway.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • 18-methoxycoronaridine (18-MC) is a novel iboga alkaloid congener with potential anti-addictive properties.
  • Previous studies indicate 18-MC acts as a potent antagonist at alpha3beta4 nicotinic receptors.
  • Alpha3beta4 nicotinic receptors are concentrated in the medial habenula and interpeduncular nucleus.

Purpose of the Study:

  • To investigate the role of the habenulo-interpeduncular pathway in 18-MC's anti-addictive effects.
  • To determine if 18-MC modulates morphine self-administration when locally administered into specific brain regions.

Main Methods:

  • Rats were trained to self-administer morphine.
  • 18-methoxycoronaridine (18-MC), mecamylamine, and alpha-conotoxin AuIB were locally administered into the medial habenula, interpeduncular nucleus, or ventral tegmental area.

Related Experiment Videos

  • Morphine and sucrose self-administration were measured.

    • Main Results:

    • Local administration of 18-MC into the medial habenula or interpeduncular nucleus significantly decreased morphine self-administration.
    • 18-MC did not affect sucrose self-administration when administered into these areas.
    • Local administration of 18-MC into the ventral tegmental area had no effect on morphine self-administration.
    • Other alpha3beta4 nicotinic antagonists produced similar effects when administered into the same brain regions.

    Conclusions:

    • The findings support the hypothesis that 18-MC reduces morphine self-administration by antagonizing alpha3beta4 nicotinic receptors within the habenulo-interpeduncular pathway.
    • This study highlights the importance of the habenulo-interpeduncular pathway in the neurobiology of opioid addiction and the potential therapeutic action of 18-MC.