Nitrous oxide may interfere with the reconsolidation of drinking memories in hazardous drinkers in a prediction-error-dependent manner.

Blocking the reconsolidation of drinking-related reward memories is a potential strategy for treating alcohol use disorders, but few pharmacological options are available for humans. This study tested whether nitrous oxide (N2O), an NMDA receptor antagonist, could reduce drinking by interfering with memory reconsolidation in 60 hazardous drinkers. Participants retrieved alcohol memories either with or without prediction error, or retrieved non-alcohol memories with prediction error, then inhaled 50% N2O for 30 minutes. The manipulation did not reduce drinking as intended based on group assignment. However, when actual experience of prediction error was assessed, N2O reduced drinking in a retrieval- and prediction-error-dependent manner. These preliminary findings highlight the importance of verifying memory reactivation procedures and suggest further investigation of N2O as a reconsolidation-blocking agent.

Study at a glance

Abstract

Weakening drinking-related reward memories by blocking their reconsolidation is a potential novel strategy for treating alcohol use disorders. However, few viable pharmacological options exist for reconsolidation interference in humans. We therefore examined whether the NMDA receptor antagonising gas, Nitrous Oxide (N2O) could reduce drinking by preventing the post-retrieval restabilisation of alcohol memories in a group of hazardous drinkers. Critically, we focussed on whether prediction error (PE; a key determinant of reconsolidation) was experienced at retrieval. Sixty hazardous drinkers were randomised to one of three groups that retrieved alcohol memories either with negative PE (Retrieval + PE), no PE (Retrieval no PE) or non-alcohol memory retrieval with PE (No-retrieval +PE). All participants then inhaled 50% N2O for 30 min. The primary outcome was change in beer consumption and alcohol cue-driven urge to drink from the week preceding manipulation (baseline) to the week following manipulation (test). The manipulation did not affect drinking following the intended retrieval+/- PE conditions However, a manipulation check, using a measure of subjective surprise, revealed that the group-level manipulation did not achieve the intended differences in PE at retrieval. Assessment of outcomes according to whether alcohol-relevant PE was actually experienced at retrieval, showed N2O produced reductions in drinking in a retrieval and PE-dependent fashion. These preliminary findings highlight the importance of directly testing assumptions about memory reactivation procedures in reconsolidation research and suggest that N2O should be further investigated as a potential reconsolidation-blocking agent.