Cholinergic Receptors and Addiction.
Cholinergic Receptors and Addiction.
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胆碱能受体和成瘾。
DOI：
10.1007/7854_2020_139
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发表时间：
2020
影响因子：
--
通讯作者：
DeBiasi,Mariella
中科院分区：
文献类型：
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作者：
Papke,RogerL;Brunzell,DarleneH;DeBiasi,Mariella
人类的行为可以通过与成瘾相关的生理或心理依赖来控制。在我们的社会中，最阴险的上瘾之一是使用含有尼古丁的烟草产品。这种成瘾可能与大脑中对天然神经递质乙酰胆碱有反应的特定受体有关。这些烟碱乙酰胆碱受体（nAChR）是由一种或多种nAChR受体亚基组装而成的配体门控离子通道。本文综述了nAChR亚基的结构和多样性，以及不同nAChR亚型在尼古丁成瘾现象中发挥的具体作用。我们重点关注含有β2和/或α6亚基的受体，以及含有α5的受体的特殊意义。这些亚型都在调节大脑中边缘奖赏通路中多巴胺介导的神经传递中起作用。我们还讨论了同源α7 nAChR在尼古丁行为反应中的独特作用，以及我们对nAChR功能多样性的了解如何有助于指导治疗尼古丁成瘾的药物治疗方法。虽然尼古丁成瘾是一个真正的全球性问题，但使用槟榔果（槟榔）产品也是一个严重的成瘾问题，与南亚大部分地区的公共卫生问题有关，影响多达6亿人。我们讨论了大脑的胆碱能受体是如何参与槟榔成瘾的，以及处理这种物质成瘾的独特挑战。
Human behavior can be controlled by physical or psychological dependencies associated with addiction. One of the most insidious addictions in our society is the use of tobacco products which contain nicotine. This addiction can be associated with specific receptors in the brain that respond to the natural neurotransmitter acetylcholine. These nicotinic acetylcholine receptors (nAChR) are ligand-gated ion channels formed by the assembly of one or multiple types of nAChR receptor subunits. In this paper, we review the structure and diversity of nAChR subunits and our understanding for how different nAChR subtypes play specific roles in the phenomenon of nicotine addiction. We focus on receptors containing β2 and/or α6 subunits and the special significance of α5-containing receptors. These subtypes all have roles in regulating dopamine-mediated neurotransmission in the mesolimbic reward pathways of the brain. We also discuss the unique roles of homomeric α7 nAChR in behavioral responses to nicotine and how our knowledge of nAChR functional diversity may help guide pharmacotherapeutic approaches for treating nicotine addiction. While nicotine addiction is a truly global problem, the use of areca nut (betel) products is also a serious addiction associated with public health issues across most of South Asia, impacting as many as 600 million people. We discuss how cholinergic receptors of the brain are also involved with areca addiction and the unique challenges for dealing with addiction to this substance.