Abstract

Addicted individuals are highly susceptible to relapse when exposed to drug-associated conditioned stimuli (CSs; “drug cues”) even after extensive periods of abstinence. Until recently, these maladaptive emotional drug memories were believed to be permanent and resistant to change. The rediscovery of the phenomenon of memory reconsolidation—by which retrieval of the memory can, under certain conditions, destabilize the previously stable memory before it restabilizes in its new, updated form—has led to the hypothesis that it may be possible to disrupt the strong maladaptive drug-memories that trigger a relapse. Furthermore, recent work has suggested that extinction training “within the reconsolidation window” may lead to a long-term reduction in relapse without the requirement for pharmacological amnestic agents. However, this so-called “retrieval-extinction” effect has been inconsistently observed in the literature, leading some to speculate that rather than reflecting memory updating, it may be the product of facilitation of extinction. In this mini review article, we will focus on factors that might be responsible for the retrieval-extinction effects on preventing drug-seeking relapse and how inter-individual differences may influence this therapeutically promising effect. A better understanding of the psychological and neurobiological mechanisms underpinning the “retrieval-extinction” paradigm, and individual differences in boundary conditions, should provide insights with the potential to optimize the translation of “retrieval-extinction” to clinical populations.

Highlights

  • Addiction is a chronic, relapsing disorder characterized by loss of control over drug use, high motivation for drug, and persistence in drug use despite adverse consequences (American Psychiatric Association, 2013)

  • Retrieval-Extinction and Relapse Prevention rediscovery of memory reconsolidation (Nader et al, 2000) interest grew in exploiting this process to develop new forms of treatment for mental health disorders including addiction

  • We focus on an alternative strategy aiming to capitalize on the hypothesized updating function of reconsolidation; reactivating a memory and introducing ‘‘CS-no US’’ information through the procedure known as ‘‘extinction within the reconsolidation window’’ or ‘‘retrieval-extinction.’’ Due to the relative paucity of drug memory retrieval-extinction studies in the literature, we will extrapolate general principles from retrieval-extinction studies of both fear and drug memories, focusing on the influence of individual differences

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Summary

Introduction

Addiction is a chronic, relapsing disorder characterized by loss of control over drug use, high motivation for drug, and persistence in drug use despite adverse consequences (American Psychiatric Association, 2013). Despite its efficacy in reducing drug-seeking, there remains a lack of definitive evidence that retrieval-extinction for drug memories depends critically upon memory-updating and reconsolidation mechanisms, and not the facilitation of extinction.

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