Related Experiment Video
Updated: Jan 12, 2026

A Prediction Error-driven Retrieval Procedure for Destabilizing and Rewriting Maladaptive Reward Memories in Hazardous Drinkers
Published on: January 5, 2018
The synergy of methylphenidate- and reconsolidation-based extinction normalizes ventromedial prefrontal function in
Ahmet O Ceceli1, Sarah G King1, K Rachel Drury1
1Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029-5674.
Abstract:
Drug-related memories can hinder abstinence goals in drug addiction. Promoting nondrugmemories via ventromedial prefrontal cortex (vmPFC)- and amygdala-guided extinctionyields mixed success. Postretrieval extinction (RE) destabilizes and updates memoriesduring reconsolidation, improving extinction. Supplementing RE, we tested methylphenidate(MPH), a dopamine agonist that promotes PFC-dependent learning and memory in cocaineuse disorder (CUD). In a proof-of-concept double-blind randomized clinical trialusing a within-subjects design, participants received oral MPH (20 mg) or placebobefore the retrieval of some of the conditioned stimuli (CS) (i.e., reminded CS+ vs.nonreminded CS+) followed by extinction; lab-simulated drug-seeking was measuredthe following day. Lower vmPFC activity following nonreminded CS+ (standardextinction) under placebo replicated the putative impairments in CUD; separately, RE (trend) and MPH conditions recruited the vmPFC, and RE's vmPFC-reliance correlatedwith drug-seeking only under placebo. Crucially, MPH-combined RE normalized cortico-limbicprocessing, bypassing the vmPFC and its amygdala connectivity. Pharmacologically-enhanced drug memory modulation may inform intervention development for addictionrecovery.
Related Concept Videos
Drug Abuse and Addiction: Pharmacological Phenomena
Desensitization and Tachyphylaxis
Drug Dependence
Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....
Drugs Affecting Neurotransmitter Release or Uptake
Combined Effects of Drugs: Synergism
Such synergistic combinations...

