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The transition from recreational use to pathological consumption is different in each individual, depending on the interaction between environmental and genetic factors. Epigenetic mechanisms are ideal candidates to study psychiatric disorders triggered by these interactions, maintaining persistent malfunctions in specific brain regions. Here we aim to study brain\u2010region\u2010specific epigenetic signatures following exposure to cocaine in a mouse model of addiction to this drug. Extreme subpopulations of vulnerable and resilient phenotypes were selected to identify miRNA signatures for differential vulnerability to cocaine addiction. We used an operant model of intravenous cocaine self\u2010administration to evaluate addictive\u2010like behaviour in rodents based on the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition criteria to diagnose substance use disorders. After cocaine self\u2010administration, we performed miRNA profiling to compare two extreme subpopulations of mice classified as resilient and vulnerable to cocaine addiction. We found that mmu\u2010miR\u201034b\u20105p was downregulated in the nucleus accumbens of vulnerable mice with high motivation for cocaine. On the other hand, mmu\u2010miR\u20101249\u20103p was downregulated on vulnerable mice with high levels of motor disinhibition. The elucidation of the epigenetic profile related to vulnerability to cocaine addiction is expected to help find novel biomarkers that could facilitate the interventions to battle this devastating disorder.<\/jats:p>","DOI":"10.1111\/adb.13201","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T04:18:56Z","timestamp":1656649136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Differential expression of miR\u20101249\u20103p and miR\u201034b\u20105p between vulnerable and resilient phenotypes of cocaine addiction"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3286-6696","authenticated-orcid":false,"given":"Laura","family":"Domingo\u2010Rodriguez","sequence":"first","affiliation":[{"name":"Laboratory of Neuropharmacology\u2010Neurophar, Department of Medicine and Life Sciences Universitat Pompeu Fabra (UPF)  Barcelona 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