Wu Jie, Gao Ming, Taylor Devin H
1] Ningbo University Medical School, Ningbo 315211, China [2] Division of Neurology and Neurobiology, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, Arizona 85013-4409, USA.
Division of Neurology and Neurobiology, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, Arizona 85013-4409, USA.
Acta Pharmacol Sin. 2014 Mar;35(3):311-5. doi: 10.1038/aps.2013.181. Epub 2014 Jan 27.
Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence. Alcoholism is a serious public health problem and has been identified as the third major cause of preventable mortality in the world. Worldwide, about 2 billion people consume alcohol, with 76.3 million having diagnosable alcohol use disorders. Alcohol is currently responsible for the death of 4% of adults worldwide (about 2.5 million deaths each year), and this number will be significantly increased by 2020 unless effective action is taken. Alcohol is the most commonly abused substance by humans. Ethanol (EtOH) is the intoxicating agent in alcoholic drinks that can lead to abuse and dependence. Although it has been extensively studied, the mechanisms of alcohol reward and dependence are still poorly understood. The major reason is that, unlike other addictive drugs (eg, morphine, cocaine or nicotine) that have specific molecular targets, EtOH affects much wider neuronal functions. These functions include phospholipid membranes, various ion channels and receptors, synaptic and network functions, and intracellular signaling molecules. The major targets in the brain that mediate EtOH's effects remain unclear. This knowledge gap results in a therapeutic barrier in the treatment of alcoholism. Interestingly, alcohol and nicotine are often co-abused, which suggests that neuronal nicotinic acetylcholine receptors (nAChRs), the molecular targets for nicotine, may also contribute to alcohol's abusive properties. Here, we briefly summarize recent lines of evidence showing how EtOH modulates nAChRs in the mesolimbic pathway, which provides a perspective that nAChRs are important targets mediating alcohol abuse.
神经元烟碱型乙酰胆碱受体是酒精奖赏和依赖的重要靶点。酒精中毒是一个严重的公共卫生问题，已被确定为全球可预防死亡的第三大主要原因。在全球范围内，约有20亿人饮酒，其中7630万人患有可诊断的酒精使用障碍。目前，酒精导致全球4%的成年人死亡（每年约250万人死亡），除非采取有效行动，到2020年这个数字将大幅增加。酒精是人类最常滥用的物质。乙醇（EtOH）是酒精饮料中的致醉剂，可导致滥用和依赖。尽管乙醇已被广泛研究，但其奖赏和依赖机制仍知之甚少。主要原因是，与其他具有特定分子靶点的成瘾药物（如吗啡、可卡因或尼古丁）不同，乙醇影响更广泛的神经元功能。这些功能包括磷脂膜、各种离子通道和受体、突触和网络功能以及细胞内信号分子。介导乙醇作用的大脑主要靶点仍不清楚。这一知识空白导致了酒精中毒治疗中的治疗障碍。有趣的是，酒精和尼古丁经常被共同滥用，这表明神经元烟碱型乙酰胆碱受体（nAChRs）作为尼古丁的分子靶点，可能也促成了酒精的滥用特性。在此，我们简要总结最近的一系列证据，展示乙醇如何调节中脑边缘通路中的nAChRs，这提供了一个视角，即nAChRs是介导酒精滥用的重要靶点。
