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      Targeting the Reconsolidation of Licit Drug Memories to Prevent Relapse: Focus on Alcohol and Nicotine

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          Abstract

          Alcohol and nicotine are widely abused legal substances worldwide. Relapse to alcohol or tobacco seeking and consumption after abstinence is a major clinical challenge, and is often evoked by cue-induced craving. Therefore, disruption of the memory for the cue–drug association is expected to suppress relapse. Memories have been postulated to become labile shortly after their retrieval, during a “memory reconsolidation” process. Interference with the reconsolidation of drug-associated memories has been suggested as a possible strategy to reduce or even prevent cue-induced craving and relapse. Here, we surveyed the growing body of studies in animal models and in humans assessing the effectiveness of pharmacological or behavioral manipulations in reducing relapse by interfering with the reconsolidation of alcohol and nicotine/tobacco memories. Our review points to the potential of targeting the reconsolidation of these memories as a strategy to suppress relapse to alcohol drinking and tobacco smoking. However, we discuss several critical limitations and boundary conditions, which should be considered to improve the consistency and replicability in the field, and for development of an efficient reconsolidation-based relapse-prevention therapy.

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          Global statistics on alcohol, tobacco and illicit drug use: 2017 status report

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            Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval.

            'New' memories are initially labile and sensitive to disruption before being consolidated into stable long-term memories. Much evidence indicates that this consolidation involves the synthesis of new proteins in neurons. The lateral and basal nuclei of the amygdala (LBA) are believed to be a site of memory storage in fear learning. Infusion of the protein synthesis inhibitor anisomycin into the LBA shortly after training prevents consolidation of fear memories. Here we show that consolidated fear memories, when reactivated during retrieval, return to a labile state in which infusion of anisomycin shortly after memory reactivation produces amnesia on later tests, regardless of whether reactivation was performed 1 or 14 days after conditioning. The same treatment with anisomycin, in the absence of memory reactivation, left memory intact. Consistent with a time-limited role for protein synthesis production in consolidation, delay of the infusion until six hours after memory reactivation produced no amnesia. Our data show that consolidated fear memories, when reactivated, return to a labile state that requires de novo protein synthesis for reconsolidation. These findings are not predicted by traditional theories of memory consolidation.
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              An Update on Memory Reconsolidation Updating.

              The reactivation of a stored memory in the brain can make the memory transiently labile. During the time it takes for the memory to restabilize (reconsolidate) the memory can either be reduced by an amnesic agent or enhanced by memory enhancers. The change in memory expression is related to changes in the brain correlates of long-term memory. Many have suggested that such retrieval-induced plasticity is ideally placed to enable memories to be updated with new information. This hypothesis has been tested experimentally, with a translational perspective, by attempts to update maladaptive memories to reduce their problematic impact. We review here progress on reconsolidation updating studies, highlighting their translational exploitation and addressing recent challenges to the reconsolidation field.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                15 April 2021
                April 2021
                : 22
                : 8
                : 4090
                Affiliations
                [1 ]School of Psychological Sciences, Tel Aviv University, Tel Aviv 69978, Israel
                [2 ]The Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel
                [3 ]Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA
                Author notes
                Author information
                https://orcid.org/0000-0002-3143-6777
                Article
                ijms-22-04090
                10.3390/ijms22084090
                8071281
                6d2eb92f-33b4-47e0-9b2a-ed6965867caf
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 20 February 2021
                : 12 April 2021
                Categories
                Review

                Molecular biology
                memory reconsolidation,addiction,alcohol,nicotine,tobacco,relapse,animal models
                Molecular biology
                memory reconsolidation, addiction, alcohol, nicotine, tobacco, relapse, animal models

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