Glick Stanley D, Ramirez Ruby L, Livi Jacklyn M, Maisonneuve Isabelle M
Center for Neuropharmacology and Neuroscience Albany Medical College, MC-136, 47 New Scotland Avenue, NY 12208, USA.
Eur J Pharmacol. 2006 May 10;537(1-3):94-8. doi: 10.1016/j.ejphar.2006.03.045. Epub 2006 Mar 24.
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.
新型伊博格生物碱同系物18-甲氧基冠狗牙花定碱（18-MC）是一种公认的抗成瘾剂，在大鼠实验中已表明，它能减少吗啡及其他滥用药物的自我给药行为。先前的研究已证实，18-MC是α3β4烟碱型受体的强效拮抗剂。由于大脑中的α3β4烟碱型受体主要位于内侧缰核和脚间核，因此开展了本研究，以确定18-MC是否能在这些脑区发挥作用，从而调节大鼠的吗啡自我给药行为。向内侧缰核或脚间区域局部注射18-MC可减少吗啡的自我给药，而对非药物强化物（蔗糖）的反应没有影响。向相同脑区局部注射另外两种α3β4烟碱型拮抗剂美加明和α-芋螺毒素AuIB也产生了类似结果。向腹侧被盖区局部注射18-MC对吗啡自我给药没有影响。这些及其他数据与以下假设一致，即18-MC通过阻断缰核-脚间通路中的α3β4烟碱型受体来减少吗啡的自我给药。
