论文标题：Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories

期刊：Nature Communications

作者：Ravi K. Das, Grace Gale et.al

发表时间：2019/11/26

数字识别码：10.1038/s41467-019-13162-w

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在提取酒精-奖赏记忆后注射单剂量氯胺酮可以破坏这些记忆的再巩固，从而降低饮酒水平。这项由90名受试者参与的研究Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories本周发表在《自然-通讯》上。

图片来源：pixabay

再巩固是一个记忆保持过程，通过让再激活的长时记忆进入短暂的不稳定状态，从而添加新的信息。一旦进入不稳定阶段，记忆会依赖N-甲基-D-天冬氨酸受体（NMDAR）通路进行重塑。研究人员认为，再巩固期间的药物干预（使用NMDAR拮抗剂，如氯胺酮）可能会削弱非适应性奖赏记忆，例如与有害药物使用行为相关的记忆。

英国伦敦大学学院的Ravi Das和同事想要确定氯胺酮是否能削弱与过量饮酒行为相关的记忆，从而降低饮酒水平。作者招募了90名有有害饮酒习惯的受试者，这些人既没有接受过酒精使用障碍的正式诊断，也没有寻求相关治疗（55位男性和35位女性，平均年龄28岁）。作者让受试者观看一系列啤酒图片，借此诱导与酒精有关的非适应性奖励记忆的提取，之后再给他们注射氯胺酮（30人）或生理盐水（30人）。作者还为另一组没有记忆提取的30名受试者注射了氯胺酮。在后续的多个随访点中，受试者被要求报告他们感知到的饮酒行为（饮酒量、享受度和渴求感）变化。作者发现，在之后9个月里，记忆提取后注射氯胺酮的疗法降低了该组成员每周饮酒天数和饮酒量。相比只注射氯胺酮，与记忆提取相结合的疗法能在更大程度上减少饮酒。

摘要：Maladaptive reward memories (MRMs) are involved in the development and maintenance of acquired overconsumption disorders, such as harmful alcohol and drug use. The process of memory reconsolidation - where stored memories become briefly labile upon retrieval - may offer a means to disrupt MRMs and prevent relapse. However, reliable means for pharmacologically weakening MRMs in humans remain elusive. Here we demonstrate that the N-methyl D-aspartate (NMDA) antagonist ketamine is able to disrupt MRMs in hazardous drinkers when administered immediately after their retrieval. MRM retrieval + ketamine (RET + KET) effectively reduced the reinforcing effects of alcohol and long-term drinking levels, compared to ketamine or retrieval alone. Blood concentrations of ketamine and its metabolites during the critical ‘reconsolidation window’ predicted beneficial changes only following MRM reactivation. Pharmacological reconsolidation interference may provide a means to rapidly rewrite maladaptive memory and should be further pursued in alcohol and drug use disorders.

（来源：科学网）