Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration.
Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration.
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介导α3Beta4烟碱拮抗剂的脑区域18-MC对甲基苯丙胺和蔗糖自我给药的影响。
DOI：
10.1016/j.ejphar.2008.09.038
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发表时间：
2008-12-03
影响因子：
5
通讯作者：
Maisonneuve IM
中科院分区：
文献类型：
--
作者：
Glick SD;Sell EM;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，减少几种滥用药物的自我管理。先前的工作已经确定18-MC是α3β4烟碱受体的有效拮抗剂。由于高密度的α3β4烟碱受体出现在内侧缰核和脚间核中，中等密度出现在背外侧被盖、腹侧被盖区和基底外侧杏仁核中，因此进行本研究以确定18-MC是否可以在这些脑区中作用以调节大鼠的甲基苯丙胺自我给药。18-MC到内侧缰核，脚间区或基底外侧杏仁核的本地管理减少甲基苯丙胺自我管理。通过将另外两种α3β4烟碱拮抗剂美加明和α-芋螺毒素AuIB局部施用到相同的脑区域中，产生了类似的结果。将18-MC或其他拮抗剂局部给予背外侧被盖或腹侧被盖区对甲基苯丙胺自我给药没有影响。与此相反，18-MC和其他拮抗剂的局部给药减少蔗糖自我管理时，给药到背外侧被盖或基底外侧杏仁核，但注入内侧缰核，脚间核，或腹侧被盖区没有影响。这些数据与以下假设一致：18-MC通过阻断缰核-脚间通路和基底外侧杏仁核中的α3β4烟碱受体间接调节多巴胺能中脑边缘通路，从而减少甲基苯丙胺自我给药。这些数据还表明，基底外侧杏仁核沿着涉及背外侧被盖中α3β4受体的不同途径介导18-MC对蔗糖自我给药的作用。
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 several drugs of abuse. Previous work has established that 18-MC is a potent antagonist at α3β4 nicotinic receptors. Because high densities of α3β4 nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine self-administration in rats. Local administration of 18-MC into either the medial habenula, the interpeduncular area or the basolateral amygdala decreased methamphetamine self-administration. Similar results were produced by local administration into the same brain areas of two other α3β4 nicotinic antagonists, mecamylamine and α-conotoxin AuIB. Local administration of 18-MC, or the other antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine self-administration. In contrast, local administration of 18-MC and the other antagonists decreased sucrose self-administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area. These data are consistent with the hypothesis that 18-MC decreases methamphetamine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. The data also suggest that the basolateral amygdala along with a different pathway involving α3β4 receptors in the dorsolateral tegmentum mediate the effect of 18-MC on sucrose self-administration.
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影响因子：
1.9
作者：
Ainge, James A.;Keating, Glenda L.;Winn, Philip
通讯作者：
Winn, Philip
影响因子：
1.7
作者：
Glick, SD;Maisonneuve, IM;Dickinson, HA
通讯作者：
Dickinson, HA
影响因子：
5
作者：
Glick, SD;Maisonneuve, IM;Fleck, MW
通讯作者：
Fleck, MW
影响因子：
3.3
作者：
EVERITT, BJ;MORRIS, KA;ROBBINS, TW
通讯作者：
ROBBINS, TW
DOI：
10.1111/j.1749-6632.1999.tb09281.x
发表时间：
1999-01-01
期刊：
ADVANCING FROM THE VENTRAL STRIATUM TO THE EXTENDED AMYGDALA
影响因子：
--
作者：
Gray, TS
通讯作者：
Gray, TS