Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories

被引：77

作者：

Das, Ravi K. ^{[1
]}

Gale, Grace ^{[1
]}

Walsh, Katie ^{[1
]}

Hennessy, Vanessa E. ^{[1
]}

Iskandar, Georges ^{[2
]}

Mordecai, Luke A. ^{[3
]}

Brandner, Brigitta ^{[3
]}

Kindt, Merel ^{[4
]}

Curran, H. Valerie ^{[1
]}

Kamboj, Sunjeev K. ^{[1
]}

机构：

[1] UCL, Clin Psychopharmacol Unit, London, England

[2] Univ Coll Hosp, Westmoreland St, London, England

[3] Univ Coll Hosp, Pain Management Ctr, London, England

[4] Univ Amsterdam, Expt Clin Psychol, Amsterdam, Netherlands

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

英国医学研究理事会;

关键词：

DISORDERS IDENTIFICATION TEST; NMDA RECEPTORS; RECONSOLIDATION; EXTINCTION; ADDICTION; RELAPSE; ANTAGONISM; RETRIEVAL;

D O I：

10.1038/s41467-019-13162-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页数：10

共 36 条

[1] NMDA receptors are critical for unleashing consolidated auditory fear memories [J].