Heydary Yasamin Hajy, Castro Emily M, Lotfipour Shahrdad, Leslie Frances M
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, USA.
Department of Emergency Medicine, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Receptors (Basel). 2025 Mar;4(1). doi: 10.3390/receptors4010001. Epub 2025 Jan 14.
The increased prevalence of electronic cigarettes, particularly among adolescents, has escalated concerns about nicotine addiction. Nicotine, a potent psychostimulant found in tobacco products, exerts its effects by interacting with nicotinic acetylcholine receptors (nAChRs) in the brain. Recent findings in both pre-clinical and clinical studies have enhanced our understanding of nAChRs, overcoming limitations of pharmacological tools that previously hindered their investigation. Of particular interest is the α6 subunit, whose expression peaks during adolescence, a critical period of brain development often marked by the initiation of substance use. Pre-clinical studies have linked α6-containing nAChRs (α6*nAChRs) to nicotine-induced locomotion, dopamine release, and self-administration behavior. Furthermore, clinical studies suggest an association between the α6 subunit and increased smoking behavior in humans. Specifically, a single nucleotide polymorphism in the 3' untranslated region of the gene that encodes for this subunit is linked to smoking behavior and other substance use. A comprehensive understanding of this subunit's role in addiction is of high importance. This review aims to consolidate current knowledge regarding the α6 subunit's functions and implications in addiction and other disorders, with the hope of paving the way for future research and the development of targeted therapies to address this pressing public health concern.
电子烟的流行率不断上升，尤其是在青少年中，这加剧了人们对尼古丁成瘾的担忧。尼古丁是烟草制品中一种强效的精神兴奋剂，它通过与大脑中的烟碱型乙酰胆碱受体（nAChRs）相互作用来发挥作用。临床前和临床研究的最新发现增进了我们对nAChRs的理解，克服了以前阻碍其研究的药理学工具的局限性。特别令人感兴趣的是α6亚基，其表达在青春期达到峰值，青春期是大脑发育的关键时期，通常以开始使用物质为标志。临床前研究已将含α6的nAChRs（α6*nAChRs）与尼古丁诱导的运动、多巴胺释放和自我给药行为联系起来。此外，临床研究表明α6亚基与人类吸烟行为增加之间存在关联。具体而言，编码该亚基的基因3'非翻译区的一个单核苷酸多态性与吸烟行为和其他物质使用有关。全面了解该亚基在成瘾中的作用非常重要。本综述旨在巩固有关α6亚基在成瘾和其他疾病中的功能及影响的现有知识，希望为未来的研究和开发针对性疗法铺平道路，以解决这一紧迫的公共卫生问题。
