{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T22:51:42Z","timestamp":1778712702599,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,7,25]],"date-time":"2011-07-25T00:00:00Z","timestamp":1311552000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Cocaine dependence is associated with orbitofrontal cortex (OFC)\u2010dependent cognitive inflexibility in both humans and laboratory animals. A critical question is whether cocaine self\u2010administration affects pre\u2010existing individual differences in cognitive flexibility. Serotonin transporter knockout (5\u2010HTT<jats:sup>\u2212\/\u2212<\/jats:sup>) mice show improved cognitive flexibility in a visual reversal learning task, whereas 5\u2010HTT<jats:sup>\u2212\/\u2212<\/jats:sup> rats self\u2010administer increased amounts of cocaine. Here we assessed: (1) whether 5\u2010HTT<jats:sup>\u2212\/\u2212<\/jats:sup> rats also show improved cognitive flexibility (next to mice); and (2) whether this is affected by cocaine self\u2010administration, which is increased in these animals. Results confirmed that na\u00efve 5\u2010HTT<jats:sup>\u2212\/\u2212<\/jats:sup> rats (<jats:italic>n<\/jats:italic>\u2003=\u20038) exhibit improved cognitive flexibility, as measured in a sucrose reinforced reversal learning task. A separate group of rats was subsequently trained to intravenously self\u2010administer cocaine (0.5\u2003mg\/kg\/infusion), and we observed that the 5\u2010HTT<jats:sup>\u2212\/\u2212<\/jats:sup> rats (<jats:italic>n<\/jats:italic>\u2003=\u200310) self\u2010administered twice as much cocaine [632.7\u2003mg\/kg (\u00b126.3)] compared with 5\u2010HTT<jats:sup>+\/+<\/jats:sup> rats (<jats:italic>n<\/jats:italic>\u2003=\u20036) [352.3\u2003mg\/kg (\u00b162.0)] over 50 1\u2010hour sessions. Five weeks into withdrawal the cocaine\u2010exposed animals were tested in the sucrose\u2010reinforced reversal learning paradigm. Interestingly, like the na\u00efve 5\u2010HTT<jats:sup>\u2212\/\u2212<\/jats:sup> rats, the cocaine exposed 5\u2010HTT<jats:sup>\u2212\/\u2212<\/jats:sup> rats displayed improved cognitive flexibility. In conclusion, we show that improved reversal learning in 5\u2010HTT<jats:sup>\u2212\/\u2212<\/jats:sup> rats reflects a pre\u2010existing trait that is preserved during cocaine\u2010withdrawal. As 5\u2010HTT<jats:sup>\u2212\/\u2212<\/jats:sup> rodents model the low activity s\u2010allele of the human serotonin transporter\u2010linked polymorphic region, these findings may have heuristic value in the treatment of s\u2010allele cocaine addicts.<\/jats:p>","DOI":"10.1111\/j.1369-1600.2011.00351.x","type":"journal-article","created":{"date-parts":[[2011,7,26]],"date-time":"2011-07-26T14:30:59Z","timestamp":1311690659000},"page":"434-440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Improved cognitive flexibility in serotonin transporter knockout rats is unchanged following chronic cocaine self\u2010administration"],"prefix":"10.1111","volume":"18","author":[{"given":"Lourens J. P.","family":"Nonkes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph H. 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