Krystal John H, Petrakis Ismene L, Krupitsky Evgeny, Schutz Christian, Trevisan Louis, D'Souza D Cyril
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Ann N Y Acad Sci. 2003 Nov;1003:176-84. doi: 10.1196/annals.1300.010.
This paper reviews clinical evidence suggesting that antagonism of the N-methyl-D-aspartate subtype of glutamate receptors by ethanol may convey an important component of the ethanol intoxication signal, that is, subjective and objective responses associated with the consumption of a large amount of ethanol. It will then review recent evidence that two phenotypes associated with increased risk for heavy alcohol consumption, recovering ethanol-dependent patients, and healthy individuals with a family history of alcohol dependence, exhibit reduced sensitivity to the dysphoric consequences of administration of the NMDA receptor antagonist, ketamine. Each of these groups displays reduced sensitivity to a potentially important response that might normally trigger the cessation of ethanol consumption. These data raise the possibility that alterations in NMDA receptor function that reduce the response to the NMDA antagonist component of ethanol may increase the risk for heavy drinking. This hypothesis is consistent with growing evidence that NMDA receptor antagonists may play a role in the treatment of alcoholism by suppressing alcohol withdrawal, reducing the development or expression of alcohol tolerance, or preventing or reversing the sensitiziation to ethanol effects.
本文回顾了临床证据，这些证据表明乙醇对谷氨酸受体的N-甲基-D-天冬氨酸亚型的拮抗作用可能传递了乙醇中毒信号的一个重要组成部分，即与大量饮用乙醇相关的主观和客观反应。然后，本文将回顾最近的证据，即与大量饮酒风险增加相关的两种表型、正在康复的乙醇依赖患者以及有酒精依赖家族史的健康个体，对NMDA受体拮抗剂氯胺酮给药后的烦躁不安后果表现出较低的敏感性。这些群体中的每一个都对一种可能通常会触发乙醇消费停止的潜在重要反应表现出较低的敏感性。这些数据提出了一种可能性，即NMDA受体功能的改变降低了对乙醇的NMDA拮抗剂成分的反应，可能会增加大量饮酒的风险。这一假设与越来越多的证据一致，即NMDA受体拮抗剂可能通过抑制酒精戒断、减少酒精耐受性的发展或表达，或预防或逆转对乙醇作用的敏化，在酒精中毒的治疗中发挥作用。
