Siciliano Cody A, Karkhanis Anushree N, Holleran Katherine M, Melchior James R, Jones Sara R
The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Handb Exp Pharmacol. 2018;248:213-238. doi: 10.1007/164_2018_106.
Alcohol use disorders are a leading public health concern, engendering enormous costs in terms of both economic loss and human suffering. These disorders are characterized by compulsive and excessive alcohol use, as well as negative affect and alcohol craving during abstinence. Extensive research has implicated the dopamine system in both the acute pharmacological effects of alcohol and the symptomology of alcohol use disorders that develop after extended alcohol use. Preclinical research has shed light on many mechanisms by which chronic alcohol exposure dysregulates the dopamine system. However, many of the findings are inconsistent across experimental parameters such as alcohol exposure length, route of administration, and model organism. We propose that the dopaminergic alterations driving the core symptomology of alcohol use disorders are likely to be relatively stable across experimental settings. Recent work has been aimed at using multiple model organisms (mouse, rat, monkey) across various alcohol exposure procedures to search for commonalities. Here, we review recent advances in our understanding of the effects of chronic alcohol use on the dopamine system by highlighting findings that are consistent across experimental setting and species.
酒精使用障碍是一个主要的公共卫生问题,在经济损失和人类痛苦方面造成了巨大代价。这些障碍的特征是强迫性和过度饮酒,以及在戒酒期间出现负面影响和对酒精的渴望。广泛的研究表明,多巴胺系统与酒精的急性药理作用以及长期饮酒后发展出的酒精使用障碍的症状学都有关联。临床前研究已经揭示了慢性酒精暴露使多巴胺系统失调的许多机制。然而,许多研究结果在诸如酒精暴露时长、给药途径和模式生物等实验参数方面并不一致。我们认为,驱动酒精使用障碍核心症状学的多巴胺能改变在不同实验环境中可能相对稳定。最近的工作旨在通过在各种酒精暴露程序中使用多种模式生物(小鼠、大鼠、猴子)来寻找共性。在此,我们通过强调在不同实验环境和物种中一致的研究结果,综述了我们对慢性酒精使用对多巴胺系统影响的最新认识进展。