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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,\n                    <jats:italic>Fosb<\/jats:italic>\n                    and\n                    <jats:italic>Npas4<\/jats:italic>\n                    , 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\n                    <jats:italic>Fosb<\/jats:italic>\n                    and\n                    <jats:italic>Npas4<\/jats:italic>\n                    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,\n                    <jats:italic>Fosb<\/jats:italic>\n                    and\n                    <jats:italic>Npas4<\/jats:italic>\n                    , in these behaviors and highlight a precise cell-type- and region-specific modulatory role of miR-1, illustrating the importance of cell-specific investigations.\n                  <\/jats:p>","DOI":"10.1038\/s41380-021-01328-2","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:02:30Z","timestamp":1637020950000},"page":"918-928","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cell-type- and region-specific modulation of cocaine seeking by micro-RNA-1 in striatal projection neurons"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5007-8004","authenticated-orcid":false,"given":"Benoit","family":"Forget","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4487-3028","authenticated-orcid":false,"given":"Elena Martin","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1732-1498","authenticated-orcid":false,"given":"Arthur","family":"Godino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura Domingo","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Kappes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Poirier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andry","family":"Andrianarivelo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric Senabre","family":"Marchan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Charlotte","family":"Allichon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e9lanie","family":"Marias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Vanhoutte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7900-1705","authenticated-orcid":false,"given":"Jean-Antoine","family":"Girault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4359-8773","authenticated-orcid":false,"given":"Rafael","family":"Maldonado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4742-7055","authenticated-orcid":false,"given":"Jocelyne","family":"Caboche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"key":"1328_CR1","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1016\/j.neuron.2011.01.017","volume":"69","author":"C Luscher","year":"2011","unstructured":"Luscher C, Malenka RC. 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