Ketamine Can Reduce Harmful Drinking by Pharmacologically Rewriting Drinking Memories

Ravi Das,Grace Gale,Katie Walsh,Vanessa Hennessy,Georges Iskandar,Luke Mordecai,Brigitta Brandner,Merel Kindt,Valerie Curran,Sunjeev Kamboj

doi:10.1016/j.biopsych.2020.02.498

Ravi Das, Grace Gale + Show 8 more

Open Access

https://doi.org/10.1016/j.biopsych.2020.02.498

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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.

Highlights

Maladaptive reward memories (MRMs) are involved in the development and maintenance of acquired overconsumption disorders, such as harmful alcohol and drug use
Plasma levels of ketamine and its metabolites are predictive of these beneficial effects only following MRM retrieval. These findings demonstrate MRM reconsolidation interference by ketamine and rewriting of reward structures surrounding alcohol
Control groups receiving retrieval or ketamine alone did not show such changes in reward-related responses to alcohol, the latter group did show some reduction in drinking

Summary

Introduction

Maladaptive reward memories (MRMs) are involved in the development and maintenance of acquired overconsumption disorders, such as harmful alcohol and drug use. Pharmacological reconsolidation interference may provide a means to rapidly rewrite maladaptive memory and should be further pursued in alcohol and drug use disorders Overconsumption disorders such as harmful drinking, alcohol and substance use disorders (AUDs, SUDs), which represent leading causes of global preventable mortality and morbidity, are fundamentally acquired or learned behaviours[1]. MRMs underlie the tendency of environmental trigger cues and contexts to grab attention and provoke motivated behavioral routines including craving[5], drug-seeking and excessive consumption They are a core mechanism underlying alcohol overconsumption and long-term relapsing behavior that must be “unlearned” for curative amelioration of problematic drinking. The temporary reconsolidation window of memory instability following reactivation offers a unique and novel mechanism to directly rewrite MRMs and strip them of their relapsogenic potential at the source[14]

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