{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:36:43Z","timestamp":1790008603566,"version":"4.0.1"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T00:00:00Z","timestamp":1584489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vulnerability to drug addiction relies on substantial individual differences. We previously demonstrated that serotonin transporter knockout (SERT<jats:sup>\u2212\/\u2212<\/jats:sup>) rats show increased cocaine intake and develop signs of compulsivity. However, the underlying neural mechanisms are not fully understood. Given the pivotal role of glutamate and prefrontal cortex in cocaine\u2010seeking behavior, we sought to investigate the expression of proteins implicated in glutamate neurotransmission in the prefrontal cortex of na\u00efve and cocaine\u2010exposed rats lacking SERT. We focused on the infralimbic (ILc) and prelimbic (PLc) cortices, which are theorized to exert opposing effects on the control over subcortical brain areas. SERT<jats:sup>\u2212\/\u2212<\/jats:sup> rats, which compared to wild\u2010type (SERT<jats:sup>+\/+<\/jats:sup>) rats show increased ShA and LgA intake short\u2010access (ShA) and long\u2010access (LgA) cocaine intake, were sacrificed 24 h into withdrawal for ex vivo molecular analyses. In the ILc homogenate of SERT<jats:sup>\u2212\/\u2212<\/jats:sup> rats, we observed a sharp increase in glial glutamate transporter 1 (GLT\u20101) after ShA, but not LgA, cocaine intake. This was paralleled by ShA\u2010induced increases in GluN1, GluN2A, and GluN2B NMDA receptor subunits and their scaffolding protein SAP102 in the ILc homogenate, but not postsynaptic density, of these knockout animals. In the PLc, we found no major changes in the homogenate; conversely, the expression of GluN1 and GluN2A NMDA receptor subunits was increased in the postsynaptic density under ShA conditions and reduced under LgA conditions. These results point to SERT as a critical regulator of glutamate homeostasis in a way that differs between the subregions investigated, the duration of cocaine exposure as well as the cellular compartment analyzed.<\/jats:p>","DOI":"10.1111\/adb.12896","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T21:17:51Z","timestamp":1584566271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The role of the serotonin transporter in prefrontal cortex glutamatergic signaling following short\u2010 and long\u2010access cocaine self\u2010administration"],"prefix":"10.1111","volume":"26","author":[{"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"}]},{"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"}]},{"given":"Boyd","family":"Van Reijmersdal","sequence":"additional","affiliation":[{"name":"Department of Cognitive Neuroscience, Division of Molecular Neurogenetics, Donders Institute for Brain, Cognition and Behaviour Radboud University Nijmegen Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Telese","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.M.","family":"Verheij","sequence":"additional","affiliation":[{"name":"Department of Cognitive Neuroscience, Division of Molecular Neurogenetics, Donders Institute for Brain, Cognition and Behaviour Radboud University Nijmegen Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-7706","authenticated-orcid":false,"given":"Fabio","family":"Fumagalli","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\/0000-0002-7621-1010","authenticated-orcid":false,"given":"Judith R.","family":"Homberg","sequence":"additional","affiliation":[{"name":"Department of Cognitive Neuroscience, Division of Molecular Neurogenetics, Donders Institute for Brain, Cognition and Behaviour Radboud University Nijmegen Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.psych.59.103006.093548"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0b013e32834d6260"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5292.1527"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-008-1212-x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12483"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.10.031"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-005-2180-z"},{"key":"e_1_2_8_9_1","first-page":"130","article-title":"Differential roles of medial prefrontal subregions in the regulation of drug seeking","volume":"2015","author":"Moorman DE","year":"1628","journal-title":"Brain Res"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2711-14.2016"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.11.008"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3119"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.10.038"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.21767\/2471-853X.100022"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12089"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2015.05.002"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005483"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.159.10.1642"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-8119(03)00113-7"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1584"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.03.010"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.306106"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1045-08.2008"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2009.11.016"},{"key":"e_1_2_8_25_1","first-page":"46","article-title":"The plasticity of extinction: contribution of the prefrontal cortex in treating addiction through inhibitory learning","volume":"4","author":"Gass JT","year":"2013","journal-title":"Front Psych"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12673"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2017.08.007"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2017.05.007"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-019-00673-9"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.110"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5387.298"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-12457-1_22"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20949"},{"issue":"3","key":"e_1_2_8_34_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1097\/01.fpc.0000184960.82903.8f","article-title":"Generation of gene knockouts and mutant models in the laboratory rat by ENU\u2010driven target\u2010selected mutagenesis","volume":"16","author":"Smits BM","year":"2006","journal-title":"Pharmacogenet Genomics"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.03.030"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2019.107610"},{"key":"e_1_2_8_37_1","volume-title":"The rat brain in stereotaxic coordinates","author":"Paxinos G","year":"2007"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-016-4315-9"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-016-9683-8"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.07.018"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.06.017"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903160305"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2016.10.002"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.04.007"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.1041309"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12822"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022600"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4595-06.2007"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5518-12.2013"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12722"}],"container-title":["Addiction Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fadb.12896","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.12896","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/adb.12896","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.12896","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T14:10:28Z","timestamp":1693663828000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/adb.12896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,18]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1111\/adb.12896"],"URL":"https:\/\/doi.org\/10.1111\/adb.12896","archive":["Portico"],"relation":{},"ISSN":["1355-6215","1369-1600"],"issn-type":[{"value":"1355-6215","type":"print"},{"value":"1369-1600","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,18]]},"assertion":[{"value":"2019-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12896"}}