Mineur Yann S, Picciotto Marina R
Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT 06508, USA.
Biochem Pharmacol. 2008 Jan 1;75(1):323-33. doi: 10.1016/j.bcp.2007.06.010. Epub 2007 Jun 14.
Human twin studies have suggested that there is a substantial genetic component underlying nicotine dependence, ongoing smoking and ability to quit. Similarly, animal studies have identified a number of genes and gene products that are critical for behaviors related to nicotine addiction. Classical genetic approaches, gene association studies and genetic engineering techniques have been used to identify the gene products involved in nicotine dependence. One class of genes involved in nicotine-related behavior is the family of nicotinic acetylcholine receptors (nAChRs). These receptors are the primary targets for nicotine in the brain. Genetic engineering studies in mice have identified a number of subunits that are critical for the ability of nicotine to activate the reward system in the brain, consisting of the dopaminergic cell bodies in the ventral tegmental area and their terminals in the nucleus accumbens and other portions of the mesolimbic system. In this review we will discuss the various lines of evidence suggesting that nAChRs may be involved in smoking behavior, and will review the human and animal studies that have been performed to date examining the genetic basis for nicotine dependence and smoking.
人类双胞胎研究表明，尼古丁依赖、持续吸烟及戒烟能力背后存在大量遗传因素。同样，动物研究也已确定了许多对与尼古丁成瘾相关行为至关重要的基因和基因产物。经典遗传学方法、基因关联研究和基因工程技术已被用于识别参与尼古丁依赖的基因产物。一类与尼古丁相关行为有关的基因是烟碱型乙酰胆碱受体（nAChRs）家族。这些受体是大脑中尼古丁的主要作用靶点。对小鼠的基因工程研究已确定了许多对尼古丁激活大脑奖赏系统的能力至关重要的亚基，该奖赏系统由腹侧被盖区的多巴胺能细胞体及其在伏隔核和中脑边缘系统其他部分的终末组成。在本综述中，我们将讨论表明nAChRs可能参与吸烟行为的各种证据，并回顾迄今为止为研究尼古丁依赖和吸烟的遗传基础而进行的人类和动物研究。
