Differential role of nicotinic acetylcholine receptor subunits in physical and affective nicotine withdrawal signs
Differential role of nicotinic acetylcholine receptor subunits in physical and affective nicotine withdrawal signs
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DOI：
10.1124/jpet.107.132977
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发表时间：
2008-04-01
影响因子：
3.5
通讯作者：
Damaj, M. I.
中科院分区：
文献类型：
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作者：
Jackson, K. J.;Martin, B. R.;Damaj, M. I.
有人认为，尼古丁戒断相关的负面影响促进了持续的烟草使用，并导致吸烟行为的高复发率。因此，重要的是要了解尼古丁戒断的受体介导的机制，以帮助开发更成功的戒烟疗法。尼古丁戒断的作用是通过烟碱乙酰胆碱受体（nAChR）介导的;然而，nAChR在尼古丁戒断中的作用仍不清楚。因此，我们使用美卡明胺沉淀，自发和条件性位置厌恶（CPA）戒断模型来测量各种nAChR敲除（KO）小鼠尼古丁戒断的身体和情感体征。通过手术植入的渗透微型泵使β 2、α 7和α 5 nAChR KO小鼠长期暴露于尼古丁。我们的研究结果显示，在β 2 KO小鼠的CPA模型中，焦虑相关行为和厌恶感的丧失，而α 7和α 5 KO小鼠分别显示尼古丁戒断诱导的痛觉过敏的丧失和躯体体征的减少。这些结果表明，含β 2的nAChR参与尼古丁戒断的情感体征，而非含β 2的nAChR与尼古丁戒断的体征更密切相关;因此，nAChR亚型组成可能在尼古丁戒断中特定亚型的参与中发挥重要作用。
It has been suggested that the negative effects associated with nicotine withdrawal promote continued tobacco use and contribute to the high relapse rate of smoking behaviors. Thus, it is important to understand the receptor-mediated mechanisms underlying nicotine withdrawal to aid in the development of more successful smoking cessation therapies. The effects of nicotine withdrawal are mediated through nicotinic acetylcholine receptors (nAChRs); however, the role of nAChRs in nicotine withdrawal remains unclear. Therefore, we used mecamylamine-precipitated, spontaneous, and conditioned place aversion (CPA) withdrawal models to measure physical and affective signs of nicotine withdrawal in various nAChR knockout (KO) mice. beta 2, alpha 7, and alpha 5 nAChR KO mice were chronically exposed to nicotine through surgically implanted osmotic minipumps. Our results show a loss of anxiety-related behavior and a loss of aversion in the CPA model in beta 2 KO mice, whereas alpha 7 and alpha 5 KO mice displayed a loss of nicotine withdrawal-induced hyperalgesia and a reduction in somatic signs, respectively. These results suggest that beta 2-containing nAChRs are involved in the affective signs of nicotine withdrawal, whereas non-beta 2-containing nAChRs are more closely associated with physical signs of nicotine withdrawal; thus, the nAChR subtype composition may play an important role in the involvement of specific subtypes in nicotine withdrawal.