Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on nicotine self-administration.
Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on nicotine self-administration.
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DOI：
10.1016/j.ejphar.2011.08.001
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发表时间：
2011-11-01
影响因子：
5
通讯作者：
Maisonneuve, Isabelle M.
中科院分区：
文献类型：
--
作者：
Glick, Stanley D.;Sell, Elizabeth M.;McCallum, Sarah E.;Maisonneuve, Isabelle M.
关键词：
18-甲氧冠孢定（18-MC）是一种公认的抗成瘾剂，已显示可减少大鼠滥用的几种药物的自我给药。18-MC是α3β4烟碱受体的有效拮抗剂。与位于内侧缰核和脚间核的高密度α3β4烟碱受体一致，18-MC已被证明在这些区域起作用，以减少吗啡和甲基苯丙胺的自我给药。本研究旨在确定18-MC对尼古丁自我给药的影响是否是通过作用于这些相同的大脑区域来介导的。由于背外侧被盖、腹侧被盖区和基底外侧杏仁核中存在中等密度的α3β4受体，因此这些脑区也被视为18-MC的潜在作用部位。将18-MC局部给药至内侧缰核、基底外侧杏仁核或背外侧被盖可降低尼古丁自我给药。令人惊讶的是，18-MC进入脚间核的局部给药增加了尼古丁自我给药，而18-MC进入腹侧被盖区的局部给药对尼古丁自我给药没有影响。通过局部施用美加明或芋螺毒素AuIB产生类似的效果。这些数据与以下假设一致：18-MC通过阻断内侧缰核、基底外侧杏仁核和背外侧被盖中的α3β4烟碱受体间接调节多巴胺能中脑边缘通路，从而减少尼古丁自我给药。数据还表明，18-MC在脚间核中的作用可能会减弱尼古丁的厌恶和/或抑郁作用。
18-methoxycoronaridine (18-MC), a putative anti-addictive agent, has been shown to decrease the self-administration of several drugs of abuse in rats. 18-MC is a potent antagonist at α3β4 nicotinic receptors. Consistent with high densities of α3β4 nicotinic receptors being located in the medial habenula and the interpeduncular nucleus, 18-MC has been shown to act in these regions to decrease both morphine and methamphetamine self-administration. The present study was conducted to determine if 18-MC’s effect on nicotine self-administration is mediated by acting in these same brain regions. Because moderate densities of α3β4 receptors occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, these brain areas were also examined as potential sites of action of 18-MC. Local administration of 18-MC into either the medial habenula, the basolateral amygdala or the dorsolateral tegmentum decreased nicotine self-administration. Surprisingly, local administration of 18-MC into the interpeduncular nucleus increased nicotine self-administration while local administration of 18-MC into the ventral tegmental area had no effect on nicotine self-administration. Similar effects were produced by local administration of either mecamylamine or conotoxin AuIB. These data are consistent with the hypothesis that 18-MC decreases nicotine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of α3β4 nicotinic receptors in the medial habenula, basolateral amygdala, and dorsolateral tegmentum. The data also suggest that an action of 18-MC in the interpeduncular nucleus may attenuate aversive and/or depressive effects of nicotine.
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影响因子：
1.7
作者：
Glick, SD;Maisonneuve, IM;Dickinson, HA
通讯作者：
Dickinson, HA
影响因子：
1.9
作者：
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通讯作者：
Winn, Philip
影响因子：
5
作者：
Glick, SD;Maisonneuve, IM;Fleck, MW
通讯作者：
Fleck, MW
影响因子：
2.5
作者：
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通讯作者：
Sesack, Susan R.
影响因子：
5.3
作者：
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通讯作者：
Shepard, Paul D.