Differential expression of miR-1249-3p and miR-34b-5p between vulnerable and resilient phenotypes of cocaine addiction

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  • dc.contributor.author Domingo Rodriguez, Laura, 1992-
  • dc.contributor.author Cabana-Domínguez, Judit
  • dc.contributor.author Fernàndez-Castillo, Noèlia
  • dc.contributor.author Cormand, Bru
  • dc.contributor.author Martín García, Elena, 1975-
  • dc.contributor.author Maldonado, Rafael, 1961-
  • dc.date.accessioned 2022-11-10T06:50:30Z
  • dc.date.available 2022-11-10T06:50:30Z
  • dc.date.issued 2022
  • dc.description.abstract Cocaine addiction is a complex brain disorder involving long-term alterations that lead to loss of control over drug seeking. 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-region-specific 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-administration to evaluate addictive-like behaviour in rodents based on the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition criteria to diagnose substance use disorders. After cocaine self-administration, we performed miRNA profiling to compare two extreme subpopulations of mice classified as resilient and vulnerable to cocaine addiction. We found that mmu-miR-34b-5p was downregulated in the nucleus accumbens of vulnerable mice with high motivation for cocaine. On the other hand, mmu-miR-1249-3p 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.
  • dc.description.sponsorship This work was supported by the Spanish “Ministerio de Economía y Competitividad-MINECO” (#SAF2017-84060-R-AEI/FEDER-UE), the Spanish “Instituto de Salud Carlos III, RETICS-RTA” (#RD12/0028/0023), the “Generalitat de Catalunya, AGAUR” (#2017 SGR-669), “ICREA-Acadèmia” (#2015) and the Spanish “Ministerio de Sanidad, Servicios Sociales e Igualdad”, “Plan Nacional Sobre Drogas of the Spanish Ministry of Health” (#PNSD-2017I068) to RM; “Fundació La Marató-TV3” (#2016/20-30), “Plan Nacional Sobre Drogas of the Spanish Ministry of Health” (#PNSD-2019I006) and NEURON-ERA-NET: MCIN/AEI/UE - PCI2021-122073-2A to E.M-G.; Spanish “Ministerio de Ciencia, Innovación y Universidades” (#RTI2018–100968-B-100), Spanish “Ministerio de Ciencia e Innovación (#PID2021-1277760B-100), “AGAUR-Generalitat de Catalunya” (#2017-SGR-738), “Plan Nacional Sobre Drogas of the Spanish Ministry of Health” (#PNSD-2017I050) and ICREA Acadèmia 2021 to BC and “Plan Nacional Sobre Drogas of the Spanish Ministry of Health” (#PNSD-2020I042) to N.F-C. The research leading to these results was also supported by the European Union H2020 Program [H2020/2014–2020] under grant agreements no 667302 (CoCA) and 728018 (Eat2beNICE) and by the “ECNP network on ADHD across the lifespan” to BC. JC-D was supported by the H2020 CoCA and Eat2beNICE projects and NF-C by “Centro de Investigación Biomédica en Red de Enfermedades Raras” (CIBERER).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Domingo-Rodriguez L, Cabana-Domínguez J, Fernàndez-Castillo N, Cormand B, Martín-García E, Maldonado R. Differential expression of miR-1249-3p and miR-34b-5p between vulnerable and resilient phenotypes of cocaine addiction. Addict Biol. 2022 Sep;27(5):e13201. DOI: 10.1111/adb.13201
  • dc.identifier.doi http://dx.doi.org/10.1111/adb.13201
  • dc.identifier.issn 1355-6215
  • dc.identifier.uri http://hdl.handle.net/10230/54781
  • dc.language.iso eng
  • dc.publisher Wiley
  • dc.relation.ispartof Addict Biol. 2022 Sep;27(5):e13201
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/667302
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018–100968-B-100
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/728018
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PCI2021-122073-2A
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-1277760B-100
  • dc.rights © 2022 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.keyword Cocaine addiction
  • dc.subject.keyword miRNA
  • dc.subject.keyword Operant conditioning
  • dc.title Differential expression of miR-1249-3p and miR-34b-5p between vulnerable and resilient phenotypes of cocaine addiction
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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