18-MC acts in the medial habenula and interpeduncular nucleus to attenuate dopamine sensitization to morphine in the nucleus accumbens

Olha Taraschenko, Joseph M. Shulan, Isabelle M. Maisonneuve, Stanley D. Glick

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

18-Methoxycoronaridine (18-MC), a novel iboga alkaloid congener, is a potential treatment for drug addiction. 18-MC has been shown to decrease self-administration of drugs (e.g., morphine, methamphetamine, nicotine) and attenuate opioid withdrawal in rats. In previous studies, systemic pretreatment with 18-MC abolished the sensitized increase in accumbens dopamine levels induced by chronic morphine administration. In vitro studies have shown that 18-MC is a potent antagonist of α3β4 nicotinic receptors, and α3β4 antagonism is believed to be the primary mechanism responsible for 18-MC's effects on drug self-administration and possibly on morphine-induced changes in mesolimbic dopamine. While there are very low densities of α3β4 nicotinic receptors in the mesolimbic pathway, these receptors are prominently localized in the medial habenula (MHb) and in the interpeduncular nucleus (IPN). These nuclei and the habenulo-interpeduncular pathway connecting them are believed to function as part of an alternate reward pathway modulating the dopaminergic mesolimbic pathway known to be involved in drug addiction. In the present study, to determine if 18-MC acts in the MHb or in the IPN, the effects of local infusion of 18-MC into these brain areas were assessed on mesolimbic dopamine responses to acute and repeated morphine treatment. Administration of 18-MC (10 μg) into either the IPN or MHb blocked the sensitized dopamine response to repeated morphine in the nucleus accumbens; 18-MC had no effect on the dopamine response to acute morphine. The results suggest that 18-MC acts in the habenulo-interpeduncular pathway to modulate the effects of repeated morphine in the dopaminergic mesolimbic system.

Original languageEnglish (US)
Pages (from-to)547-560
Number of pages14
JournalSynapse
Volume61
Issue number7
DOIs
StatePublished - Jul 1 2007

Fingerprint

Habenula
Nucleus Accumbens
Morphine
Dopamine
Self Administration
Nicotinic Receptors
Substance-Related Disorders
Tabernaemontana
18-methoxycoronaridine
Interpeduncular Nucleus
Methamphetamine
Nicotine
Reward
Alkaloids
Pharmaceutical Preparations
Opioid Analgesics

Keywords

  • Drug addiction
  • Habenulo-interpeduncular pathway
  • Mesolimbic pathway
  • Opioids

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology
  • Advanced and Specialized Nursing

Cite this

18-MC acts in the medial habenula and interpeduncular nucleus to attenuate dopamine sensitization to morphine in the nucleus accumbens. / Taraschenko, Olha; Shulan, Joseph M.; Maisonneuve, Isabelle M.; Glick, Stanley D.

In: Synapse, Vol. 61, No. 7, 01.07.2007, p. 547-560.

Research output: Contribution to journalArticle

Taraschenko, Olha ; Shulan, Joseph M. ; Maisonneuve, Isabelle M. ; Glick, Stanley D. / 18-MC acts in the medial habenula and interpeduncular nucleus to attenuate dopamine sensitization to morphine in the nucleus accumbens. In: Synapse. 2007 ; Vol. 61, No. 7. pp. 547-560.
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