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Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories

Das, RK; Gale, G; Walsh, K; Hennessy, VE; Iskandar, G; Mordecai, LA; Brandner, B; ... Kamboj, SK; + view all (2019) Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories. Nature Communications , 10 (1) , Article 5187. 10.1038/s41467-019-13162-w. Green open access

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Abstract

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.

Type: Article
Title: Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-019-13162-w
Publisher version: https://doi.org/10.1038/s41467-019-13162-w
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ - With correction dated 11 June 2020.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Clinical, Edu and Hlth Psychology
URI: https://discovery.ucl.ac.uk/id/eprint/10086992
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