Department of Anesthesiology, Rutgers, The State University of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA; Department of Pharmacology, Physiology and Neuroscience, Rutgers, The State University of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Department of Anesthesiology, Rutgers, The State University of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA; Department of Pharmacology, Physiology and Neuroscience, Rutgers, The State University of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Pharmacol Biochem Behav. 2017 Nov;162:94-102. doi: 10.1016/j.pbb.2017.06.005. Epub 2017 Jun 15.
Alcohol use disorder (AUD) or alcoholism is a chronic relapsing disorder. Our knowledge of alcoholism hinges on our understanding of its effects on the brain. This review will center on the effects of alcohol in the lateral habenula (LHb), an epithalamic structure that connects the forebrain with the midbrain and encodes aversive signaling. Like many addictive drugs, alcohol has both rewarding and aversive properties. While alcohol's euphoric property is believed to be important for the initiation of drinking, increasing evidence suggests that alcohol's negative affect plays a critical role in excessive drinking and alcohol dependence. During withdrawal and abstinence, alcoholics often experience anxiety and depressions, both of which have been implicated in relapse drinking. This review focuses on the recent accumulation of knowledge about the effects of acute and chronic alcohol exposure on the activity of and synaptic transmissions on LHb neurons, as well as the effects of manipulation of LHb function on alcohol consumption and related behaviors. Recent evidence highlights a critical role for the LHb in AUD and related psychiatric ailments. Multidisciplinary work in animals collectively suggests that LHb function and activity, including M-type potassium channels and glutamatergic transmission are altered by acute and repeated chronic alcohol exposure. We will also discuss how functional, pharmacological, and chemogenetic manipulation of the LHb affects ethanol drinking and psychiatric disorders occurring in animals withdrawn from chronic alcohol exposure. Conceivable mechanisms behind these effects and their potential as targets for therapies will also be discussed.
酒精使用障碍（AUD）或酗酒是一种慢性复发性疾病。我们对酗酒的认识取决于我们对其对大脑影响的理解。这篇综述将集中讨论酒精对外侧缰核（LHb）的影响，LHb 是连接前脑和中脑的丘脑结构，编码厌恶信号。与许多成瘾药物一样，酒精既有奖励作用，也有厌恶作用。虽然人们认为酒精的欣快作用对饮酒的开始很重要，但越来越多的证据表明，酒精的负面情绪在过量饮酒和酒精依赖中起着关键作用。在戒断和禁欲期间，酗酒者经常会感到焦虑和抑郁，这两者都与复发饮酒有关。这篇综述重点介绍了关于急性和慢性酒精暴露对 LHb 神经元活动和突触传递的影响的最新知识积累，以及对 LHb 功能的操作对酒精消费和相关行为的影响。最近的证据强调了 LHb 在 AUD 和相关精神疾病中的关键作用。动物的多学科工作共同表明，LHb 的功能和活动，包括 M 型钾通道和谷氨酸能传递，会受到急性和重复慢性酒精暴露的改变。我们还将讨论 LHb 的功能、药理学和化学遗传操作如何影响乙醇摄入以及从慢性酒精暴露中戒断的动物中出现的精神障碍。还将讨论这些影响背后的潜在机制及其作为治疗靶点的潜力。
