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Nonetheless, the conditioned stimulus (CS) memory retrieval\u2010extinction procedure is ineffective in inhibiting drug craving and relapse after prolonged withdrawal, which significantly undermines its therapeutic potential. In the present study, we showed that, unlike the CS memory retrieval\u2010extinction procedure, noncontingent heroin injections (unconditioned stimulus [UCS]) 1\u00a0hour before the extinction sessions decreased the heroin\u2010priming\u2010induced reinstatement, renewal, and spontaneous recovery of heroin seeking after 28\u00a0days of withdrawal (ie, remote heroin\u2010associated memories) in rats. The UCS retrieval manipulation induced reactivation of the basolateral amygdala (BLA) after prolonged withdrawal, and this reactivation was absent with the CS retrieval manipulation. Chemogenetic inactivation of the BLA abolished the inhibitory effect of the UCS memory retrieval\u2010extinction procedure on heroin\u2010priming\u2010induced reinstatement after prolonged withdrawal. Furthermore, the combination of chemogenetic reactivation of BLA and CS retrieval\u2010extinction procedure resembled the inhibitory effect of UCS retrieval\u2010extinction procedure on heroin seeking after prolonged withdrawal. We also observed that the inhibitory effect of the UCS retrieval\u2010extinction procedure is mediated by regulation of AMPA receptor endocytosis in the BLA. Our results demonstrate critical engagement of the BLA in reconsolidation updating of heroin\u2010associated memory after prolonged withdrawal, extending our knowledge of the boundary conditions of the reconsolidation of drug\u2010associated memories.<\/jats:p>","DOI":"10.1111\/adb.12793","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T13:26:53Z","timestamp":1563974813000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Basolateral amygdala is required for reconsolidation updating of heroin\u2010associated memory after prolonged withdrawal"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3498-8163","authenticated-orcid":false,"given":"Kai","family":"Yuan","sequence":"first","affiliation":[{"name":"Peking University Sixth Hospital\/Peking University Institute of Mental Health Peking University  Beijing China"},{"name":"Peking\u2010Tsinghua 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