Pharmacological and behavioral reconsolidation manipulations for targeting maladaptive drug memories in humans 

Sandra Helinski

Ravi Das


The destabilisation and subsequent reconsolidation of memories following retrieval offers a unique opportunity for updating the inflexible, maladaptive motivational memories (MMMs) linking predictive cues with alcohol reward that drive relapse in alcohol use disorder (AUD). Neutralising the relapse-promoting impact of MMMs via reconsolidation interference could profoundly improve the long-term treatment of AUDs. This may be achieved either through pharmacological blockade of reconsolidation with N-methyl D-aspartate receptor (NMDAR) antagonists or behavioural ‘updating’ of MMM content during the reconsolidation window. However, there are difficulties in translating preclinical work, particularly with regards to availability of suitable reconsolidation-blocking drugs in man and the resistance to destabilisation of well-learned MMMs such as those in AUDs.  I will present work examining the prerequisites for MMM detsabilisation at retrieval and the effects of behavioural (counterconditioning or cognitive reappraisal) and pharmacological (Nitrous Oxide) interventions post-destabilisation on markers of maladaptive alcohol use.