Most Dana, Ferguson Laura, Harris R Adron
Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX, USA.
Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX, USA.
Handb Clin Neurol. 2014;125:89-111. doi: 10.1016/B978-0-444-62619-6.00006-9.
Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy.
急性酒精中毒会导致大脑中的细胞变化,这种变化会持续数小时,而长期饮酒会在神经系统中引发广泛的神经适应性变化,这种变化可能会持续一生。长期饮酒以及发展为酒精依赖涉及由酒精产生的基因表达变化所导致的突触重塑。饮酒、酗酒和酒精依赖的发展过程可分为几个阶段,包括中毒、戒断和渴望。每个阶段都与基因表达、细胞功能、脑回路以及最终行为的特定变化相关。从娱乐性饮酒(急性)转变为酒精依赖(慢性)背后的分子机制是什么?哪些细胞适应性变化导致药物记忆的保留,从而导致成瘾行为持续存在,即使在长期戒断药物之后?对酒精中毒神经生物学的研究旨在回答这些问题。本章将描述饮酒和酒精依赖所引起的分子适应性变化,并概述酒精中毒在分子水平上的关键神经化学参与者,这些也是潜在的治疗靶点。