Nat Commun 10, 5187 (2019). https://doi.org/10.1038/s41467-019-13162-w
Das, R.K., Gale, G., Walsh, K. et al.
Department of Psychiatry, the Department of Neuroscience, the Department of Anesthesiology, the Department of Pharmacology and Systems Therapeutics, and the Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York; the Department of Anesthesiology and the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston; the Michael E. DeBakey VA Medical Center, Houston; and the Center for Clinical Research and Evidence-Based Medicine, University of Texas Medical School at Houston.
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.