The genetic components of alcohol and nicotine co-addiction: from genes to behavior.
The genetic components of alcohol and nicotine co-addiction: from genes to behavior.
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DOI：
10.2174/1874473710801020124
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发表时间：
2008-05
期刊：
影响因子：
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通讯作者：
I. Schlaepfer;Nicole R. Hoft;M. Ehringer
中科院分区：
文献类型：
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作者：
I. Schlaepfer;Nicole R. Hoft;M. Ehringer
人类酒精和尼古丁成瘾的同时发生是有据可查的，并且有充分的证据表明共同的基因可能导致这两种疾病。尽管通过收养、双胞胎和家庭研究已经明确了导致吸烟和酗酒问题的遗传因素，但具体基因仍有待确定，其作用方式仍有待阐明。最近的人类遗传学研究提供的证据表明，神经元烟碱乙酰胆碱受体（nAChR）基因可能在调节早期行为中发挥作用，这些行为是酒精和尼古丁依赖的危险因素，例如开始年龄和对药物的早期主观反应。综合证据表明，当尼古丁和/或饮酒激活时，多巴胺能系统可能在调节奖励的愉悦感方面发挥重要作用。 nAChR 是多巴胺能奖赏系统的重要组成部分，因为一些受体已被证明可以激活多巴胺的释放，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发生改变。此外，其他神经递质回路（包括 GABA、谷氨酸和血清素）之间复杂的相互作用可能会受到 nAChR 的调节，这使得研究人员能够研究不同药物共享的涉及神经生物学的基因。未来的研究旨在了解这些基因之间的变异及其相应的功能含义，将有助于阐明烟碱受体基因的自然变异如何导致这些常见的共病疾病。
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.