Cell-type- and region-specific modulation of cocaine seeking by micro-RNA-1 in striatal projection neurons

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• dc.contributor.author Forget, Benoit
• dc.contributor.author Martín García, Elena, 1975-
• dc.contributor.author Godino, Arthur
• dc.contributor.author Domingo Rodriguez, Laura, 1992-
• dc.contributor.author Kappes, Vincent
• dc.contributor.author Poirier, Pierre
• dc.contributor.author Andrianarivelo, Andry
• dc.contributor.author Senabre, Eric
• dc.contributor.author Allichon, Marie-Charlotte
• dc.contributor.author Marias, Mélanie
• dc.contributor.author Vanhoutte, Peter
• dc.contributor.author Girault, Jean-Antoine
• dc.contributor.author Maldonado, Rafael, 1961-
• dc.contributor.author Caboche, Jocelyne
• dc.date.accessioned 2021-12-15T07:30:33Z
• dc.date.available 2021-12-15T07:30:33Z
• dc.date.issued 2022
• dc.description.abstract The persistent and experience-dependent nature of drug addiction may result in part from epigenetic alterations, including non-coding micro-RNAs (miRNAs), which are both critical for neuronal function and modulated by cocaine in the striatum. Two major striatal cell populations, the striato-nigral and striato-pallidal projection neurons, express, respectively, the D1 (D1-SPNs) and D2 (D2-SPNs) dopamine receptor, and display distinct but complementary functions in drug-evoked responses. However, a cell-type-specific role for miRNAs action has yet to be clarified. Here, we evaluated the expression of a subset of miRNAs proposed to modulate cocaine effects in the nucleus accumbens (NAc) and dorsal striatum (DS) upon sustained cocaine exposure in mice and showed that these selected miRNAs were preferentially upregulated in the NAc. We focused on miR-1 considering the important role of some of its predicted mRNA targets, Fosb and Npas4, in the effects of cocaine. We validated these targets in vitro and in vivo. We explored the potential of miR-1 to regulate cocaine-induced behavior by overexpressing it in specific striatal cell populations. In DS D1-SPNs miR-1 overexpression downregulated Fosb and Npas4 and reduced cocaine-induced CPP reinstatement, but increased cue-induced cocaine seeking. In DS D2-SPNs miR-1 overexpression reduced the motivation to self-administer cocaine. Our results indicate a role of miR1 and its target genes, Fosb and Npas4, in these behaviors and highlight a precise cell-type- and region-specific modulatory role of miR-1, illustrating the importance of cell-specific investigations.
• dc.description.sponsorship This work was supported by Fondation pour la Recherche Médicale (DEQ20150734352 to JC), Centre National pour la Recherche Scientifique (CNRS, B.F., A.G., V.K., P.P., P.V., J.C.), Institut National pour la Santé et la Recherche Médicale (INSERM; B.F., A.G., V.K., P.P., P.V., J.-A.G., J.C.), Sorbonne Université, Faculté des Sciences et Ingénierie (B.F., A.G., V.K., P.P., P.V., J.-A.G., J.C.) Labex Biopsy Investissements d’Avenir, ANR-11-IDEX-0004-02 (B.F., A.G., V.K., P.P., P.V., J.-A.G., J.C.), the Spanish Ministerio de Economía y Competitividad-MINECO (#SAF2017-84060-R-AEI/FEDER-UE; E.M.-G., L.D.-R., R.M.), the Spanish Instituto de Salud Carlos III, RETICS-RTA (#RD12/0028/0023; E.M.-G., L.D.-R., R.M.), the Generalitat de Catalunya, AGAUR (#2017-SGR-669; E.M.-G., L.D.-R., R.M.), ICREA-Acadèmia (#2015) and the Spanish Ministerio de Sanidad, Servicios Sociales e Igualdad, Plan Nacional Sobre Drogas (#PNSD-2017I068) to R.M., Fundació La Marató-TV3 (#2016/20-30) to E.M.-G. Fondation pour la Recherche Médicale (FRM#DPA20140629798) and ANR (ANR-16-CE16-0018) to J.A.G.
• dc.format.mimetype application/pdf
• dc.identifier.citation Forget B, Garcia EM, Godino A, Rodriguez LD, Kappes V, Poirier P, Andrianarivelo A, Marchan ES, Allichon MC, Marias M, Vanhoutte P, Girault JA, Maldonado R, Caboche J. Cell-type- and region-specific modulation of cocaine seeking by micro-RNA-1 in striatal projection neurons. Mol Psychiatry. 2022 Feb;27(2):918-28. DOI: 10.1038/s41380-021-01328-2
• dc.identifier.doi http://dx.doi.org/10.1038/s41380-021-01328-2
• dc.identifier.issn 1359-4184
• dc.identifier.uri http://hdl.handle.net/10230/49213
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Mol Psychiatry. 2022 Feb;27(2):918-28
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-84060-R
• dc.rights © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Molecular biology
• dc.subject.keyword Neuroscience
• dc.subject.keyword Physiology
• dc.title Cell-type- and region-specific modulation of cocaine seeking by micro-RNA-1 in striatal projection neurons
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion