Rewriting the valuation and salience of alcohol-related stimuli via memory reconsolidation.

R K Das,S K Kamboj,W Lawn

doi:10.1038/tp.2015.132

Abstract

The transient period of memory instability that can be triggered when memories are retrieved under certain conditions offers an opportunity to modify the maladaptive memories at the heart of substance use disorders (SUDs). However, very well-learned memories (such as those in excessive drinking and alcohol use disorders) are resistant to destabilisation when retrieved or may not destabilise at all. Memory retrieval and intervention procedures that reliably destabilise and update maladaptive motivational memories may help to improve the long-term treatment of SUDs. In 59 hazardous drinkers, we tested a novel retrieval procedure for destabilising well-learned cue-drinking memory networks that maximises prediction error (PE) via guided expectancy violation during retrieval of these memories. This was compared with a retrieval procedure without PE and no-retrieval controls. We subsequently counterconditioned alcohol cues with disgusting tastes and images in all groups and assessed responding to alcohol stimuli 1 week later. Counterconditioning following PE retrieval produced generalised reductions in oculomotor attentional bias, explicit valuation and outcome expectancies in response to alcohol cues 1 week after intervention, evidence of updating of distributed motivational drinking memory networks. These findings demonstrate that well-learned cue-drinking memories can be destabilised and that learning history need not constrain memory destabilisation if PE is maximised at retrieval. Broad rewriting of diverse aspects of maladaptive memory by counterconditioning is achievable following this procedure. The procedure described may provide a platform for the development of novel memory-modifying interventions for SUDs.

Highlights

In the progression from recreational to hazardous drug use to fullblown addiction, maladaptive motivational memory (MMM)associations are formed that link environmental drug-related stimuli, and the availability, intoxicating and rewarding effects of drugs themselves.[1]
It may be possible to rewrite the content of destabilised MMMs with more adaptive learning during the reconsolidation window, which could be potentially transformative in the longterm treatment of addiction
The apparent resistance of old and strongly trained memories to destabilisation poses a serious challenge to the use of reconsolidation to ‘fix’ maladaptive memories in substance use disorders (SUDs)

Summary

INTRODUCTION

In the progression from recreational to hazardous drug use to fullblown addiction, maladaptive motivational memory (MMM). The REACT no PE (n = 20) and REACT+PE (n = 20) groups were given a 150 ml glass of (alcohol-free, unknown to participants, to avoid alcohol effects on subsequent task performance) beer and instructed they would drink it all, according to on-screen prompts, after alcohol pictures were rated for pleasantness (an index of beer cue valuation). Verbal fluency and category fluency, digit span,[51] trail-making[52] and digit cancellation tasks were performed immediately to fill 10 min following the reactivation procedures These high working-memory load tasks were chosen to ensure disengagement of cue-beer memory networks prior to counterconditioning.[53] The 10-min space between retrieval and counterconditioning was based on previous studies successfully employing this space in prototypical retrieval-extinction paradigms.[9,12,13].

RESULTS

Findings

DISCUSSION