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      A critical perspective on updating drug memories through the integration of memory editing and brain stimulation

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          Abstract

          Addiction is a persistent, recurring condition characterized by repeated relapses despite the desire to control drug use or maintain sobriety. The attainment of abstinence is hindered by persistent maladaptive drug-associated memories, which drive drug-seeking and use behavior. This article examines the preliminary evidence supporting the combination of non-invasive brain stimulation (NIBS) techniques and memory editing (or reconsolidation) interventions as add-on forms of treatment for individuals with substance-related disorders (SUD). Studies have shown that NIBS can modestly reduce drug use and craving through improved cognitive control or other undetermined reasons. Memory reconsolidation, a process by which a previously consolidated memory trace can be made labile again, can potentially erase or significantly weaken SUD memories underpinning craving and the propensity for relapse. This approach conveys enthusiasm while also emphasizing the importance of managing boundary conditions and null results for interventions found on fear memory reconsolidation. Recent studies, which align with the state-dependency and activity-selectivity hypotheses, have shown that the combination of NIBS and behavioral interventions holds promise for treating SUD by reducing self-reported and physiological aspects of craving. Effective long-term outcomes for this procedure require better identification of critical memories, a deeper understanding of the brain mechanisms underlying SUD and memory reconsolidation and overcoming any boundary conditions of destabilized memories. This will enable the procedure to be personalized to the unique needs of individual patients.

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          Most cited references102

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          Neurobiology of addiction: a neurocircuitry analysis.

          Drug addiction represents a dramatic dysregulation of motivational circuits that is caused by a combination of exaggerated incentive salience and habit formation, reward deficits and stress surfeits, and compromised executive function in three stages. The rewarding effects of drugs of abuse, development of incentive salience, and development of drug-seeking habits in the binge/intoxication stage involve changes in dopamine and opioid peptides in the basal ganglia. The increases in negative emotional states and dysphoric and stress-like responses in the withdrawal/negative affect stage involve decreases in the function of the dopamine component of the reward system and recruitment of brain stress neurotransmitters, such as corticotropin-releasing factor and dynorphin, in the neurocircuitry of the extended amygdala. The craving and deficits in executive function in the so-called preoccupation/anticipation stage involve the dysregulation of key afferent projections from the prefrontal cortex and insula, including glutamate, to the basal ganglia and extended amygdala. Molecular genetic studies have identified transduction and transcription factors that act in neurocircuitry associated with the development and maintenance of addiction that might mediate initial vulnerability, maintenance, and relapse associated with addiction.
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            Drug Addiction: Updating Actions to Habits to Compulsions Ten Years On.

            A decade ago, we hypothesized that drug addiction can be viewed as a transition from voluntary, recreational drug use to compulsive drug-seeking habits, neurally underpinned by a transition from prefrontal cortical to striatal control over drug seeking and taking as well as a progression from the ventral to the dorsal striatum. Here, in the light of burgeoning, supportive evidence, we reconsider and elaborate this hypothesis, in particular the refinements in our understanding of ventral and dorsal striatal mechanisms underlying goal-directed and habitual drug seeking, the influence of drug-associated Pavlovian-conditioned stimuli on drug seeking and relapse, and evidence for impairments in top-down prefrontal cortical inhibitory control over this behavior. We further review animal and human studies that have begun to define etiological factors and individual differences in the propensity to become addicted to drugs, leading to the description of addiction endophenotypes, especially for cocaine addiction. We consider the prospect of novel treatments for addiction that promote abstinence from and relapse to drug use.
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              Neural systems of reinforcement for drug addiction: from actions to habits to compulsion.

              Drug addiction is increasingly viewed as the endpoint of a series of transitions from initial drug use--when a drug is voluntarily taken because it has reinforcing, often hedonic, effects--through loss of control over this behavior, such that it becomes habitual and ultimately compulsive. Here we discuss evidence that these transitions depend on interactions between pavlovian and instrumental learning processes. We hypothesize that the change from voluntary drug use to more habitual and compulsive drug use represents a transition at the neural level from prefrontal cortical to striatal control over drug seeking and drug taking behavior as well as a progression from ventral to more dorsal domains of the striatum, involving its dopaminergic innervation. These neural transitions may themselves depend on the neuroplasticity in both cortical and striatal structures that is induced by chronic self-administration of drugs.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                14 April 2023
                2023
                : 14
                : 1161879
                Affiliations
                [1] 1Laboratoire de Psychologie Médicale et d’Addictologie, Faculty of Medicine, Université Libre de Bruxelles (ULB) , Brussels, Belgium
                [2] 2Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB) , Brussels, Belgium
                Author notes

                Edited by: Marco Diana, University of Sassari, Italy

                Reviewed by: Marcello Solinas, Institut National de la Santé et de la Recherche Médicale (INSERM), France

                *Correspondence: Xavier Noël, Xavier.Noel@ 123456ulb.be

                This article was submitted to Addictive Disorders, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2023.1161879
                10140428
                53086870-7733-4114-a6f1-8ba30ff93419
                Copyright © 2023 Noël.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 February 2023
                : 27 March 2023
                Page count
                Figures: 0, Tables: 1, Equations: 0, References: 103, Pages: 8, Words: 8106
                Categories
                Psychiatry
                Mini Review

                Clinical Psychology & Psychiatry
                addiction,memory reconsolidation,non-invasive brain stimulation,memory editing,substance use disorders

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