The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational study

作者：Jing-Li Yue, Kai Yuan, Yanping Bao, Shiqiu Meng, Le Shi, Qing Fang, Xiaojie Guo, Lu Cao, Yekun Sun, Tangsheng Lu, Na Zeng, Wei Yan, Ying Han, Jie Sun, Jie Shi, Thomas R. Kosten, Yan-Xue Xue, Ping Wu, Lin Lü · 发表于：EBioMedicine · 年份：2022 · DOI：10.1016/j.ebiom.2022.104283 · 被引用次数：16 · 研究领域：Memory and Neural Mechanisms、Neurotransmitter Receptor Influence on Behavior、Sleep and Wakefulness Research

Background Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder. An unconditioned stimulus (US)-triggers a memory reconsolidation updating procedure (MRUP) that has been developed and demonstrated its effectiveness in decreasing relapse to cocaine and heroin in preclinical models. However, utilizations of abused drugs as the US to initiate MRUP can be problematic. We therefore designed a translational rat study and human study to evaluate the efficacy of a novel methadone-initiated MRUP. Methods In the rodent study, male rats underwent heroin self-administration training for 10 consecutive days, and were randomly assigned to receive saline or methadone at 10 min, 1 h or 6 h before extinction training after 28-day withdrawal. The primary outcome was operant heroin seeking after reinstatement. In the human experimental study, male OUD patients were randomly assigned to get MRUP at 10 min or 6 h after methadone or methadone alone. The primary outcomes included experimental cue-induced heroin craving change, sustained abstinence and retention in the study at post intervention and the 5 monthly follow-up assessments. The secondary outcomes were changes in physiological responses including experimental cue-induced blood pressure and heart rate. Findings Methadone exposure but not saline exposure at 10 min or 1 h before extinction decreased heroin-induced reinstatement of heroin seeking after 28-day of withdrawal in rats (F (8,80) = 8.26, p < 0.001). In the human st...