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

European Journal of Pharmacology
S D GlickI M Maisonneuve

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 morphine and other drugs of abuse. Previous work has established that 18-MC is a potent antagonist at alpha3beta4 nicotinic receptors. Because alpha3beta4 nicotinic receptors in the brain are preferentially located in the medial habenula and the interpeduncular nucleus, the present study was conducted to determine if 18-MC could act in these brain areas to modulate morphine self-administration in rats. Local administration of 18-MC into either the medial habenula or the interpeduncular area decreased morphine self-administration while having no effect on responding for a non-drug reinforcer (sucrose). 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 into the ventral tegmental area had no effect on morphine self-administration. These and other data are consistent with the hypothesis that 18-MC decreases morphine self-administration by blocking alpha3beta4 nicotinic receptors in the habenulo-interpeduncular pathway.

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Citations

Jan 27, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Lawrence TollFrances M Leslie
Feb 21, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sharon R GradyCecilia Gotti
May 9, 2013·Pharmacology, Biochemistry, and Behavior·Nichole M NeugebauerMarina R Picciotto
Jan 25, 2012·Progress in Neurobiology·L SheltonD Borsook
Jun 7, 2011·The International Journal of Biochemistry & Cell Biology·Hugo R AriasKrzysztof Jozwiak
Nov 18, 2009·Pharmacology & Therapeutics·Bianca Jupp, Andrew J Lawrence
May 16, 2009·Neuroscience Letters·Sarah E McCallum, Stanley D Glick
Jun 30, 2009·Seminars in Cell & Developmental Biology·Rachel E Penton, Robin A J Lester
Jun 2, 2009·Biochemical Pharmacology·Cecilia GottiMichele Zoli
Aug 30, 2011·European Journal of Pharmacology·Stanley D GlickIsabelle M Maisonneuve
Feb 17, 2015·Drug and Alcohol Dependence·Christopher S TallaridaScott M Rawls
Apr 16, 2014·Frontiers in Human Neuroscience·Kenia M VelasquezRamiro Salas
Feb 13, 2018·Addiction Biology·Alberto J LópezMarcelo A Wood
Mar 22, 2020·Molecular Pharmacology·D EacretJ A Blendy
Feb 23, 2017·Neuroscience and Biobehavioral Reviews·Marc Fakhoury

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