18-methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine self-administration in rats
18-methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine self-administration in rats
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DOI：
10.1016/j.ejphar.2006.03.045
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发表时间：
2006-05-10
影响因子：
5
通讯作者：
Maisonneuve, IM
中科院分区：
文献类型：
--
作者：
Glick, SD;Ramirez, RL;Maisonneuve, IM
新的iboga生物碱同源物18-甲氧基冠苷（18-MC）是一种公认的抗成瘾剂，已被证明，在大鼠中，减少吗啡和其他药物滥用的自我管理。先前的工作已经确定18-MC是004烟碱受体的有效拮抗剂。由于α 3 β 4烟碱受体在大脑中优先位于内侧缰核和脚间核，本研究进行，以确定是否18-MC可以在这些脑区调节吗啡自我管理在大鼠。18-MC到内侧缰或脚间区的局部给药减少吗啡自我管理，而对非药物的应答（蔗糖）没有影响。类似的结果产生的局部给药到相同的大脑区域的其他两个0 4烟碱拮抗剂，美加明和α-芋螺毒素AuIB。腹侧被盖区局部注射18-MC对吗啡自身给药无影响。这些和其他数据是一致的假设，即18-MC通过阻断004烟碱受体的缰-脚间通路减少吗啡自我管理。(c)2006 Elsevier B. V.保留所有权利。
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 004 nicotinic receptors. Because alpha 3 beta 4 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 0 4 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 004 nicotinic receptors in the habernulo-interpeduncular pathway. (c) 2006 Elsevier B.V. All rights reserved.