Reconsolidation-disruption diminishes spontaneous and stress-induced cocaine seeking

Abstract

BACKGROUNDThere has been a recent surge of interest in exploiting the process of reconsolidation to weaken maladaptive memories, in the hope this will drive the next wave of innovation in psychotherapy. Reconsolidation normally functions to stabilise and maintain memories in the long-term, and is critical in enabling memory updating. However, this process can be disrupted pharmacologically to weaken memories, or harnessed to allow destructive interference of a memory trace. Work has already begun to exploit this mechanism to disrupt pavlovian fear memories in the treatment of maladaptive anxiety and threat processing, and additionally being able to target instrumental memories may provide further clinical benefit.\n\nMETHODSExpanding our rat intravenous (i.v.) self-administration paradigm, we tested whether disruption of instrumental memory reconsolidation with the noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 could reduce relapse of cocaine seeking in response to stress, drug-priming or presentation of a drug-associated cue.\n\nRESULTSSpontaneous responding for i.v. cocaine was reduced by reconsolidation-disruption. Furthermore, responding was not rescued by pharmacologically-induced stress. However, responding was restored following systemic administration of the drug, or presentation of a drug-associated cue.\n\nCONCLUSIONSThese data are consistent with hypothesis that there exist multiple routes to relapse, and suggest that at least some of these routes could be blocked by reconsolidation-disruption. This work provides important proof-of-principle that reconsolidation based therapies are a viable means of reducing the rates of relapse in substance use disorders.