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Recent studies suggest that the potentiation of glutamatergic transmission at the orbitofrontal cortex (OFC) to dorsal striatum (DS) synapses drives the transition from controlled to compulsion-like SA. However, the timing of the induction of this synaptic plasticity remains elusive. Here, mice were first allowed to intravenously self-administer cocaine. When mice had to endure a risk of electrical foot shock, only a fraction persevered in cocaine SA. In these persevering mice, we recorded high A\/N ratios (AMPA-R\/NMDA-R: \u03b1-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid receptor\/N-methyl-D-aspartate receptor) in both types of spiny projection neurons (i.e., D1 and D2 dopamine receptor-expressing SPNs). By contrast, when we prepared slices at the end of the acquisition period, in all mice, the A\/N was high in D1R- but not D2R-SPNs. These results indicate that the transition to compulsion-like cocaine SA emerges during the punishment sessions, where synapses onto D2R-SPNs are strengthened. In renouncing individuals, the cocaine-evoked strengthening in D1R-SPNs is lost. Our study thus reveals the cell-type specific sequence of the induction of plasticity that eventually may cause compulsion-like SA.<\/jats:p>","DOI":"10.1038\/s41386-022-01429-8","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T15:03:08Z","timestamp":1662562988000},"page":"448-458","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Cell-type specific synaptic plasticity in dorsal striatum is associated with punishment-resistance compulsive-like cocaine self-administration in mice"],"prefix":"10.1038","volume":"48","author":[{"given":"Vincent","family":"Pascoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Hiver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Esmaeili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7917-4596","authenticated-orcid":false,"given":"Christian","family":"L\u00fcscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,7]]},"reference":[{"key":"1429_CR1","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1001\/archpsyc.1995.03950150051010","volume":"52","author":"LA Warner","year":"1995","unstructured":"Warner LA, Kessler RC, Hughes M, Anthony JC, Nelson CB. 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