Molecular mechanisms underlying behaviors related to nicotine addiction.
Molecular mechanisms underlying behaviors related to nicotine addiction.
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DOI：
10.1101/cshperspect.a012112
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发表时间：
2013-01-01
影响因子：
5.4
通讯作者：
Kenny PJ
中科院分区：
文献类型：
--
作者：
Picciotto MR;Kenny PJ
吸烟每年导致超过 500 万人死亡，几乎占所有肺癌死亡人数的 90%。尼古丁是烟草烟雾的主要增强成分，通过神经元烟碱乙酰胆碱受体（nAChR）在大脑中发挥作用。 nAChR 是变构调节的配体门控离子通道，由五个跨膜亚基组成。十二个哺乳动物α亚基（α2-α10）和三个β亚基（β2-β4）已被克隆。哺乳动物大脑中主要的 nAChR 亚型是含有 α4 和 β2 亚基的亚型（表示为 α4β2* nAChR）。 α4β2* nAChR 介导许多与尼古丁成瘾相关的行为，并且是目前批准的戒烟剂的主要目标。考虑到大脑中存在大量的 nAChR 亚基，除 α4 和 β2 之外，含有亚基的 nAChR 很可能也在吸烟中发挥作用。事实上，分别编码 α5、α3 和 β4 nAChR 亚基的 CHRNA5-CHRNA3-CHRNB4 基因簇的遗传变异已被证明会增加对烟草依赖和吸烟相关疾病（包括肺癌）的脆弱性。此外，α5 或 β4 亚基表达经过基因改造的小鼠极大地改变了尼古丁的消耗模式。除了尼古丁的强化特性外，尼古丁对食欲、注意力和情绪的影响也被认为有助于吸烟习惯的建立和维持。在这里，我们回顾了对尼古丁行为作用以及所涉及的 nAChR 亚型的最新见解，这些亚型可能导致吸烟者形成烟草依赖。
Tobacco smoking results in more than 5 million deaths each year and accounts for almost 90 percent of all deaths from lung cancer. Nicotine, the major reinforcing component of tobacco smoke, acts in the brain through the neuronal nicotinic acetylcholine receptors (nAChRs). The nAChRs are allosterically regulated, ligand-gated ion channels consisting of five membrane-spanning subunits. Twelve mammalian α subunits (α2-α10) and three β subunits (β2-β4) have been cloned. The predominant nAChR subtypes in mammalian brain are those containing α4 and β2 subunits (denoted as α4β2* nAChRs). The α4β2* nAChRs mediate many behaviors related to nicotine addiction, and are the primary targets for currently approved smoking cessation agents. Considering the large number of nAChR subunits in the brain, it is likely that nAChRs containing subunits in addition to α4 and β2 also play a role in tobacco smoking. Indeed, genetic variation in the CHRNA5-CHRNA3-CHRNB4 gene cluster, encoding the α5, α3 and β4 nAChR subunits, respectively, has been shown to increase vulnerability to tobacco dependence and smoking-associated diseases including lung cancer. Moreover, mice in which expression of α5 or β4 subunits has been genetically modified have profoundly altered patterns of nicotine consumption. In addition to the reinforcing properties of nicotine, the effects of nicotine on appetite, attention and mood are also thought to contribute to establishment and maintenance of the tobacco smoking habit. Here, we review recent insights into the behavioral actions of nicotine, and the nAChRs subtypes involved, which likely contribute to the development of tobacco dependence in smokers.
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DOI：
10.1523/jneurosci.2258-10.2010
发表时间：
2010-07-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bailey CD;De Biasi M;Fletcher PJ;Lambe EK
通讯作者：
Lambe EK
影响因子：
3.6
作者：
Drenan, Ryan M.;Nashmi, Raad;Lester, Henry A.
通讯作者：
Lester, Henry A.
影响因子：
10.6
作者：
Caldarone, BJ;Harrist, A;Picciotto, MR
通讯作者：
Picciotto, MR
DOI：
10.1038/npp.2011.299
发表时间：
2012-04
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
DOHERTY, K;KINNUNEN, T;GARVEY, AJ
通讯作者：
GARVEY, AJ