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与尼古丁药理学和成瘾相关的分子机制

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

作者信息

Fowler Christie D, Turner Jill R, Imad Damaj M

机构信息

Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA.

出版信息

Handb Exp Pharmacol. 2020;258:373-393. doi: 10.1007/164_2019_252.

Abstract

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation.

摘要

烟草依赖是全球可预防疾病和死亡的主要原因。尼古丁是卷烟中的主要精神活性成分,其汽化形式(源自电子烟设备)也越来越受欢迎。因此,需要了解尼古丁药理学和依赖背后的分子机制,以确定治疗药物依赖的新方法。在本章中,我们回顾了该领域目前对尼古丁在大脑中的作用、药物依赖背后的神经回路、调节烟碱型乙酰胆碱受体功能的因素以及特定基因在减轻尼古丁依赖易感性方面的作用的理解。除了尼古丁在大脑中的直接作用外,还发现尼古丁和烟草产品中的其他成分会改变药物使用情况,因此,提供证据以突出这一问题。最后,讨论了目前可用的药物治疗策略,以及实现长期戒烟目标的未来治疗方向展望。

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