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We have previously demonstrated that rats with ablation of the serotonin transporter (SERT<jats:sup>\u2212\/\u2212<\/jats:sup> rats) show increased cocaine intake reminiscent of compulsivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>By comparing SERT<jats:sup>\u2212\/\u2212<\/jats:sup> to SERT<jats:sup>+\/+<\/jats:sup> rats, we investigated whether SERT deletion influences glutamate homeostasis under control conditions as well as after short access (ShA: 1\u2009h per session) or long access (LgA: 6\u00a0h per session) to cocaine self\u2010administration. Rats were killed at 24\u2009h after the last self\u2010administration session for ex vivo molecular analyses of the main determinants of the glutamate system, including transporters (vesicular and glial), receptors (main post\u2010synaptic subunits of NMDA and AMPA receptors together with the metabotropic subunit mGLUR5), and scaffolding proteins (SAP102, SAP97, and GRIP) in the NAc shell (sNAc)<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In cocaine\u2010naive animals, SERT deletion was associated with changes indicative for a reduction in glutamate signalling. ShA and LgA exposure led to a further dysregulation of the glutamatergic synapse.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SERT deletion may render the glutamatergic synapses of the NAc shell more responsive to both ShA and LgA intake of cocaine.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15823","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T05:36:44Z","timestamp":1645076204000},"page":"3727-3739","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Responsivity of serotonin transporter knockout rats to short and long access to cocaine: Modulation of the glutamate signalling in the nucleus accumbens shell"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8045-3146","authenticated-orcid":false,"given":"Lucia","family":"Caffino","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8172-1384","authenticated-orcid":false,"given":"Francesca","family":"Mottarlini","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2933-2677","authenticated-orcid":false,"given":"Giorgia","family":"Targa","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel M. 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