Suppression of methamphetamine-seeking behavior by nicotinic agonists
Suppression of methamphetamine-seeking behavior by nicotinic agonists
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DOI：
10.1073/pnas.0600347103
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发表时间：
2006-05-30
影响因子：
11.1
通讯作者：
Yamamoto, Tsuneyuki
中科院分区：
文献类型：
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作者：
Hiranita, Takato;Nawata, Yoko;Yamamoto, Tsuneyuki
为了从烟碱型乙酰胆碱能传递的角度了解甲基苯丙胺（MAP）渴求的机制，我们采用MAP自我给药的大鼠模型，研究了烟碱型激动剂产生抗渴求效应的脑内负责部位。全身性尼古丁和乙酰胆碱酯酶抑制剂氯奈哌齐通过激活丘脑核、前边缘皮质、杏仁核和海马中的烟碱乙酰胆碱能受体而非毒蕈碱乙酰胆碱能受体，减弱MAP寻求行为的恢复。在这些区域中，除了海马，我们还发现了功能差异，在这种恢复。尼古丁拮抗剂美加明单独没有恢复MAP寻求行为。这些结果表明，烟碱乙酰胆碱能传递的失活可能是MAP寻求行为出现的一个重要因素，因此，失活状态的正常化可能导致对恢复的抑制。我们的研究结果还表明，在负责的大脑子区域中存在功能差异。将这一观点扩展到MAP依赖的治疗，我们的研究结果表明，烟碱乙酰胆碱能传递的激活剂是可能的抗痉挛剂。
To understand the mechanism of methamphetamine (MAP) craving from the viewpoint of nicotinic acetylcholinergic transmission, we examined the responsible site of the brain for anticraving effects produced by nicotinic agonists by using a MAP self-administration paradigm in rats. Systemic nicotine and an acetylcholinesterase inhibitor, clonepezil, attenuated the reinstatement of MAP-seeking behavior by means of the activation of nicotinic acetylcholinergic receptors, but not muscarinic acetylcholinergic receptors, in the nucleus accumbens core, prelimbic cortex, amygdala, and hippocampus. Among these regions, with the exception of the hippocampus, we also found functional differences in this reinstatement. The nicotinic antagonist mecamylamine alone did not reinstate MAP-seeking behavior. These results suggest that the inactivation of nicotinic acetylcholinergic transmission may be an essential factor in the appearance of MAP-seeking behavior, and, thus, the normalization of the inactivated state may result in the suppression of the reinstatement. Our findings also indicate that there are functional differences in the responsible brain subregions. Extending this view to the treatment of MAP dependence, our results suggest that activators of nicotinic acetylcholinergic transmission are possible anticraving agents.