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Pharmacological interventions targeting drug\u2010associated memories hold promise for curbing relapse by impeding the process of memory reconsolidation, predominantly governed by cAMP signalling. Exchange Protein Activated by cAMP (Epac) serves as a distinctive mediator of cAMP signalling, which has been implicated in reinforcing the effects of cocaine and facilitating the acquisition. Nonetheless, the role of Epac in heroin\u2010related memory and the subsequent seeking behaviour remains enigmatic. In this study, we explored the impact of Epac activation on the reconsolidation process of drug\u2010related memories associated with heroin self\u2010administration. Over the course of 10 consecutive days, rats underwent training, wherein they acquired the behaviour of nose poking to obtain heroin accompanied by a tone\u2009+\u2009light cue. This nose\u2010poking behaviour was subsequently extinguished when heroin infusion and cue presentation were discontinued. Subsequently, we administered 8\u2010pCPT\u2010cAMP (8\u2010CPT), an Epac\u2010specific activator, into the basolateral amygdala at various time points, either in the presence or absence of a conditioned stimulus. Our findings demonstrate that administering 8\u2010CPT immediately after memory retrieval effectively reduces cue\u2010 and heroin\u2010induced reinstatement, with the observed effects persisting significantly for a minimum of 28\u2009days. However, infusion of 8\u2010CPT for a duration of 6\u00a0h following the memory retrieval trial, or without it altogether, had no discernible impact. Thus, these findings strongly suggest that Epac activation can disrupt the reconsolidation of heroin\u2010associated memory, thereby diminishing the reinstatement of heroin\u2010seeking behaviour.<\/jats:p>","DOI":"10.1111\/adb.13330","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T08:04:50Z","timestamp":1693901090000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Activation of Epac in the BLA disrupts reconsolidation and attenuates heroin\u2010seeking behaviour"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8489-5686","authenticated-orcid":false,"given":"Shihao","family":"Huang","sequence":"first","affiliation":[{"name":"National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence Peking University  Beijing China"},{"name":"Department of Neurobiology, School of Basic Medical Sciences Peking University Health 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