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Quantitative Analysis of Nicotinic Acetylcholine Receptors in Human Brain ; Effects of Aging and Smoking Cessation

人脑中烟碱乙酰胆碱受体的定量分析；

基本信息

批准号：
17591263
负责人：
ISHIZU Koichi
金额：
$ 1.98万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591263/
关键词：
5IA nicotine SPECT smoking neuroreceptor ニコチン受容体 nAChR 定量禁煙

项目摘要

Nicotinic acetylcholine receptors (nAChRs) are of great interest because they are implicated in various brain functions. They also are thought to play an important role in nicotine addiction of smokers. Chronic (-)-nicotine, a nAChR agonist, treatment in mice and rats elicits a dose-dependent increase in nAChRs in the brain. Upregulation of nAChRs in postmortem human brains of smokers has also been reported. However, changes in nAChRs after smoking cessation of smoking in humans are poorly understood. The aim of this study was to detect the dynamic changes of nAChRs after smoking and smoking cessation in the brains of living subjects. We performed [^<123>I]-5IA SPECT in non-smokers and smokers (n=16) who had quit smoking for 4 h, 10 days, and 21 days and calculated and compared distribution volumes (Vt) of [^<123>I]-5IA. The binding potential of nAChRs (Vt of the [^<123>I]-5IA) in the brains of smokers decreased by 33.5% ± 10.5% after 4 hours of smoking cessation ; increased by 25.7% ± 9.2% after 10 days of smoking cessation ; and decreased to the level of non-smokers in after 21 days of smoking cessation. Since the upregulation of the nicotinic acetylcholine receptors of the smokers after chronic exposure of the nicotine was downregulated to the non-smokers' level by around 21 days after smoking cessation, the upregulation is a temporary effect. Thus, a decrease in the number of nicotine receptors to the level in nonsmokers may be a step in overcoming nicotine dependence.

烟碱乙酰胆碱受体（nAChR）引起了人们极大的兴趣，因为它们与各种大脑功能有关。它们还被认为在吸烟者的尼古丁成瘾中发挥着重要作用。慢性 (-)-尼古丁（一种 nAChR 激动剂）对小鼠和大鼠进行治疗会引起大脑中 nAChR 的剂量依赖性增加。吸烟者死后大脑中 nAChR 的上调也有报道。然而，人们对人类戒烟后 nAChR 的变化知之甚少。本研究的目的是检测活体受试者吸烟和戒烟后大脑中nAChRs的动态变化。我们对非吸烟者和戒烟4小时、10天和21天的吸烟者(n=16)进行了[^123I]-5IA SPECT，计算并比较了[^123I]-5IA的分布体积(Vt)。戒烟4小时后，吸烟者大脑中nAChRs的结合电位（[^123I]-5IA的Vt）下降了33.5%±10.5%；戒烟10天后增加25.7%±9.2%；戒烟21天后下降到不吸烟者的水平。由于长期接触尼古丁后吸烟者烟碱乙酰胆碱受体的上调在戒烟后21天左右下调至非吸烟者的水平，因此这种上调是暂时的效果。因此，将尼古丁受体的数量减少到不吸烟者的水平可能是克服尼古丁依赖的一个步骤。