Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 11 2019
26 11 2019
Historique:
received:
11
03
2019
accepted:
18
10
2019
entrez:
28
11
2019
pubmed:
28
11
2019
medline:
14
4
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31772157
doi: 10.1038/s41467-019-13162-w
pii: 10.1038/s41467-019-13162-w
pmc: PMC6879579
doi:
Substances chimiques
Biomarkers
0
Ketamine
690G0D6V8H
norketamine
XQY6JVF94X
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5187Subventions
Organisme : Medical Research Council
ID : MR/M007006/1
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Références
Am J Psychiatry. 2005 Aug;162(8):1414-22
pubmed: 16055762
J Exp Psychol Gen. 2014 Oct;143(5):2020-45
pubmed: 25111580
Neuropharmacology. 2018 Nov;142:72-82
pubmed: 29339294
Psychopharmacology (Berl). 2012 Feb;219(3):751-61
pubmed: 21766171
Neuropsychopharmacology. 2008 Jan;33(1):166-80
pubmed: 17805308
Annu Rev Clin Psychol. 2013;9:215-48
pubmed: 23537484
Science. 2012 Apr 13;336(6078):241-5
pubmed: 22499948
Psychopharmacology (Berl). 2018 Sep;235(9):2507-2527
pubmed: 30091003
Biol Psychiatry. 2014 Dec 15;76(12):970-6
pubmed: 24821196
Addiction. 2000 Jun;95(6):889-900
pubmed: 10946438
Addiction. 1993 Jun;88(6):791-804
pubmed: 8329970
Psychopharmacology (Berl). 2013 Apr;226(4):659-72
pubmed: 22638814
JAMA Psychiatry. 2017 Mar 1;74(3):224-232
pubmed: 28146250
Neuropsychopharmacology. 2010 Jan;35(1):217-38
pubmed: 19710631
J Vis Exp. 2018 Jan 5;(131):
pubmed: 29364255
Addiction. 2002 Feb;97(2):155-67
pubmed: 11860387
Neurosci Biobehav Rev. 2013 Mar;37(3):240-55
pubmed: 23261501
Biol Psychiatry. 2002 Nov 15;52(10):976-86
pubmed: 12437938
Neurobiol Learn Mem. 2013 Mar;101:26-32
pubmed: 23305621
Nat Neurosci. 2006 Oct;9(10):1237-9
pubmed: 16998481
Science. 2013 Feb 15;339(6121):830-3
pubmed: 23413355
Learn Mem. 2011 May 16;18(6):357-66
pubmed: 21576515
Learn Mem. 2004 Sep-Oct;11(5):579-85
pubmed: 15466312
Neurobiol Learn Mem. 2011 Nov;96(4):609-23
pubmed: 21376820
Alcohol Alcohol. 2015 Mar;50(2):244-50
pubmed: 25534931
Neurobiol Learn Mem. 2018 Oct;154:78-86
pubmed: 29474957
JAMA Psychiatry. 2017 Mar 1;74(3):214-223
pubmed: 28146243
Trends Neurosci. 2009 Aug;32(8):413-20
pubmed: 19640595
J Neurosci. 2008 Aug 13;28(33):8230-7
pubmed: 18701685
Neurosci Biobehav Rev. 2012 Apr;36(4):1119-39
pubmed: 22285426
Transl Psychiatry. 2015 Sep 22;5:e645
pubmed: 26393491
Clin Psychol Rev. 2000 Mar;20(2):173-89
pubmed: 10721496