S2A-3 The Alpha6*-nAChR is A Highly Sensitive Target for Low Dose Alcohol
作者机构:Division of NeurologyBarrow Neurological InstituteSt.Joseph’s Hospital and Medical CenterPhoenix AZ 85013USA
出 版 物:《神经药理学报》 (Acta Neuropharmacologica)
年 卷 期:2018年第8卷第4期
页 面:36-37页
学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题:EtOH mediate the sensitivity
摘 要:Alcohol use disorder(AUD)is a serious public health problem that affects approximately 17 million Americans and results in tremendous social,legal and medical costs to the *** other addictive drugs(e.g.,morphine,cocaine or nicotine)that have specific molecular targets,ethanol(EtOH)has no specific *** most previous studies,EtOH concentrations used for investigation were too high(e.g.,50 mmol·L-1)compared to the EtOH concentrations in human brain after alcohol drinking,and the high dose EtOH may produce nonspecific modulations of a variety of receptors,ion channels,intracellular signaling cascades,and gene expression in the ***,it is important to understand low dose(e.g.,10 mmol·L-1)EtOH effects in the ***,the molecular and cellular targets that mediate the sensitivity to low dose EtOH remain to be *** containingα6 subunits(α6*-nAChRs)shows a highly restricted distribution in midbrain dopaminergic neurons that are associated with drug dependence and ***,we report that low dose EtOH(0.1~5 mmol·L-1)significantly potentiatesα6*-nAChR function using patch-clamp whole-cell *** EtOH modulatesα6*-nAChR-mediated function depending on both EtOH and nicotine concentrations,representing a positive allosteric *** conclusion,our results demonstrate a functionalα6*-nAChR transfected in human SH-EP1 cells that can be used as an excellent cell model to investigateα6*-nAChR function and *** patch-clamp recording condition,low dose EtOH modulatesα6*-nAChR function as a positive allosteric *** this mechanism,brainα6*-nAChRs may play a critical role in mediating low dose alcohol’effects on alcohol reward and dependence.