Laboratory for Integrative Neuroscience, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
Laboratory for Integrative Neuroscience, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
Neuron. 2017 Dec 20;96(6):1223-1238. doi: 10.1016/j.neuron.2017.10.032.
Ethanol is one of the most commonly abused drugs. Although environmental and genetic factors contribute to the etiology of alcohol use disorders, it is ethanol's actions in the brain that explain (1) acute ethanol-related behavioral changes, such as stimulant followed by depressant effects, and (2) chronic changes in behavior, including escalated use, tolerance, compulsive seeking, and dependence. Our knowledge of ethanol use and abuse thus relies on understanding its effects on the brain. Scientists have employed both bottom-up and top-down approaches, building from molecular targets to behavioral analyses and vice versa, respectively. This review highlights current progress in the field, focusing on recent and emerging molecular, cellular, and circuit effects of the drug that impact ethanol-related behaviors. The focus of the field is now on pinpointing which molecular effects in specific neurons within a brain region contribute to behavioral changes across the course of acute and chronic ethanol exposure.
乙醇是最常被滥用的药物之一。尽管环境和遗传因素促成了酒精使用障碍的病因，但正是乙醇在大脑中的作用解释了（1）急性乙醇相关行为变化，如兴奋剂随后是抑制剂效应，以及（2）行为的慢性变化，包括使用量增加、耐受性、强迫性寻求和依赖。因此，我们对乙醇使用和滥用的认识依赖于对其对大脑影响的理解。科学家们分别采用了自下而上和自上而下的方法，从分子靶点构建到行为分析，反之亦然。本综述重点介绍了该领域的最新进展，关注药物对与乙醇相关行为有影响的最新和新兴的分子、细胞和回路效应。该领域的重点现在是确定在特定脑区的特定神经元中的哪些分子效应导致了急性和慢性乙醇暴露过程中的行为变化。
