Long-term behavioural rewriting of maladaptive drinking memories via reconsolidation-update mechanisms

Abstract

Background Alcohol use disorders can be conceptualised as a learned pattern of maladaptive alcohol-consumption behaviours. The memories encoding these behaviours centrally contribute to long-term excessive alcohol consumption and are therefore an important therapeutic target. The transient period of memory instability sparked during memory reconsolidation offers a therapeutic window to directly rewrite these memories using targeted behavioural interventions. However, clinically-relevant demonstrations of the efficacy of this approach are few. We examined key retrieval parameters for destabilising naturalistic drinking memories and the ability of subsequent counterconditioning to effect long-term reductions in drinking. Methods Hazardous/harmful beer-drinking volunteers (N = 120) were factorially randomised to retrieve (RET) or not retrieve (No RET) alcohol reward memories with (PE) or without (No PE) alcohol reward prediction error. All participants subsequently underwent disgust-based counterconditioning of drinking cues. Acute responses to alcohol were assessed pre- and post-manipulation and drinking levels were assessed up to 9 months. Results Greater long-term reductions in drinking were found when counterconditioning was conducted following retrieval (with and without PE), despite a lack of short-term group differences in motivational responding to acute alcohol. Large variability in acute levels of learning during counterconditioning was noted. ‘Responsiveness’ to counterconditioning predicted subsequent responses to acute alcohol in RET + PE only, consistent with reconsolidation-update mechanisms. Conclusions The longevity of behavioural interventions designed to reduce problematic drinking levels may be enhanced by leveraging reconsolidation-update mechanisms to rewrite maladaptive memory. However, inter-individual variability in levels of corrective learning is likely to determine the efficacy of reconsolidation-updating interventions and should be considered when designing and assessing interventions.

A proposal for the unification of psychotherapeutic action understood as memory modification processes.

“…Laboratory studies of more complex design indicate the ecological validity of the unlearning sequence, as noted earlier. The fact that the unlearning sequence is defined as certain subjective experiences, rather than particular procedures, has allowed it to be fulfilled in creative ways in various empirical studies of its therapeutic application: Gray et al (2017, 2020) and Iyadurai et al (2018) report the successful use of specialized protocols designed for posttraumatic stress disorder rooted in a single event, and various protocols have been developed and applied for particular addictions (e.g., alcohol addiction: Gale et al, 2021; cocaine seeking: Luo et al, 2015; heroin craving: Xue et al, 2012; nicotine addiction: Germeroth et al, 2017; internet gaming addiction: Zhao et al, 2022). The protocol developed by Högberg et al (2011) for suicidal adolescents eliminated their posttraumatic symptomology in a small number of therapy sessions, and an analysis of that protocol by Ecker (2018, pp.…”

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

“…Interference with memory reconsolidation by post-retrieval counterconditioning has also been successfully tested in humans [ 56 ], showing particularly promising results in modulating craving and drinking patterns in hazardous alcohol drinkers [ 54 , 74 , 75 ]. As in other reconsolidation studies from this group, alcohol-associated memories were retrieved by presenting abstinent participants with a glass of beer and then taking it away unexpectedly before the first sip [ 29 , 54 , 74 , 76 ].…”

“…Immediately after memory retrieval, alcohol cues were re-associated with gustatory disgust, leading to subsequent reduction in alcohol cue valuation, attentional capture, and alcohol craving [ 54 , 74 ]. Moreover, the same group showed that disgust-based counterconditioning of drinking cues conducted following memory retrieval led to greater long-term reductions in drinking (9 months) in hazardous drinkers [ 75 ]. These findings suggest that the retrieval-counterconditioning manipulation leads to integration of the new information into the memory, by “rewriting” the valence of alcohol cues in humans.…”

Imagining the Future to Reshape the Past: A Path to Combine Cue Extinction and Memory Reconsolidation With Episodic Foresight for Addiction Treatment

“…To begin the drug-related memory reconsolidation process, patients could be presented with drug cues that make them mentally travel back in time and retrieve the emotional experiences for further elaboration. Previously conducted trials that implemented behavioral memory reconsolidation interventions were often supplemented by extinction-enhancing pharmacological treatments such as D-cycloserine (10)(11)(12) or βadrenergic antagonists like Propranolol (13,14) and have shown to be impactful in terms of drug cue reactivity extinction (15)(16)(17). Positive results in the extinction of drug cue reactivity are suggested to be highly dependent on the efficiency of reactivating maladaptive drug memories (18,19), and that comes as no surprise that drug cue-exposure seems like a promising strategy for aiding retrieval and reactivation of such memories.…”