Schlaepfer Isabel R, Hoft Nicole R, Ehringer Marissa A
Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA.
Curr Drug Abuse Rev. 2008 Jun;1(2):124-34. doi: 10.2174/1874473710801020124.
Co-occurrence of alcohol and nicotine addiction in humans is well documented and there is good evidence that common genes may contribute to both disorders. Although genetic factors contributing to tobacco and alcohol problem use have been well established through adoption, twin and family studies, specific genes remain to be identified and their mode of action elucidated. Recent work from human genetics studies has provided evidence that neuronal nicotinic acetylcholine receptors (nAChR) genes may have a role in mediating early behaviors that are risk factors for alcohol and nicotine dependence, such as age of initiation and early subjective responses to the drugs. Converging evidence suggests that the dopaminergic system is likely to be important in mediating the pleasurable feelings of reward when activated by nicotine and/or alcohol consumption. The nAChRs are important components of the dopaminergic reward system because some of the receptors have been shown to activate the release of dopamine, and mice lacking genes for specific nAChR gene subunits show altered behavioral responses to nicotine and alcohol. Furthermore, complex interactions between other neurotransmitter circuits including GABA, glutamate and serotonin may be modulated by nAChRs, leading researchers to study genes involved in neurobiology shared by different drugs. Future studies aimed at understanding the variation among these genes, and their corresponding functional implications, will help elucidate how natural variants in nicotinic receptor genes contribute to these common co-morbid disorders.
酒精成瘾与尼古丁成瘾在人类中共存的现象已有充分记录，并且有充分证据表明，某些共同基因可能导致这两种成瘾症。尽管通过收养、双胞胎和家族研究已充分证实遗传因素会导致烟草和酒精问题使用，但仍有待确定具体基因并阐明其作用方式。人类遗传学研究的最新成果表明，神经元烟碱型乙酰胆碱受体（nAChR）基因可能在介导早期行为方面发挥作用，这些早期行为是导致酒精和尼古丁依赖的危险因素，例如开始使用的年龄以及对这些药物的早期主观反应。越来越多的证据表明，多巴胺能系统在由尼古丁和/或酒精消费激活时，可能在介导愉悦的奖赏感方面发挥重要作用。nAChRs是多巴胺能奖赏系统的重要组成部分，因为已证明某些受体可激活多巴胺的释放，并且缺乏特定nAChR基因亚基基因的小鼠对尼古丁和酒精的行为反应会发生改变。此外，包括γ-氨基丁酸（GABA）、谷氨酸和血清素在内的其他神经递质回路之间的复杂相互作用可能受nAChRs调节，这促使研究人员研究不同药物共有的神经生物学相关基因。旨在了解这些基因之间差异及其相应功能影响的未来研究，将有助于阐明烟碱受体基因中的自然变异如何导致这些常见的共病。
