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Addiction\u2010related memories, like strong aversive memories, are often highly resistant to extinction and can continue to drive relapse long after drug use has ceased. These enduring behavioral effects suggest that drug engrams, sparsely distributed neural ensembles encoding drug\u2010associated experiences, are stabilized by powerful synaptic and molecular plasticity. At the same time, their very malleability may hold the key to developing new treatments. This minireview synthesizes emerging findings on drug engrams, highlighting the specialized circuits, molecular mechanisms, and behavioral consequences tied to addiction\u2010related memory traces. We focus on how engram tagging and reactivation techniques have revealed addiction\u2010specific ensembles across several brain regions and important pathways that promote or attenuate drug\u2010seeking behavior. We also discuss how direct manipulation of drug engrams may hold promise for weakening the influence of drug\u2010associated cues and other relapse triggers, while enhancing protective circuits to reduce relapse risk. Still, fundamental questions remain such as how do drug engrams evolve during the transition from recreational use to addiction? Addressing these questions will be critical for developing circuit\u2010informed, lasting interventions that target the memory systems sustaining addiction.<\/jats:p>","DOI":"10.1002\/hipo.70040","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T22:17:00Z","timestamp":1759789020000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Drug\u2010Related Engrams and Their Role in the Persistence and Recurrence of Drug\u2010Related Behaviors"],"prefix":"10.1002","volume":"35","author":[{"given":"M.","family":"Cutler","sequence":"first","affiliation":[{"name":"Department of Psychology (Neuroscience) Loyola University Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Thati","sequence":"additional","affiliation":[{"name":"Department of Psychology (Neuroscience) Loyola University Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7828-4029","authenticated-orcid":false,"given":"S. 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