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Relapse risks are even greater in addicts with comorbid depression, perhaps because they use drugs to alleviate depressive symptoms. Only a few preclinical studies have examined this comorbidity, mostly exploring depressive\u2010like effects following drug exposure. We examined rats from two different depression\u2010like models: (a) chronic\u2010mild\u2010stress (CMS), which respond to antidepressant medications and (b) depressed\u2010rat\u2010line (DRL), a genetic model of selective breeding, which is less responsive to antidepressant medications. We tested addictive behaviors in a cocaine self\u2010administration procedure, including the \u201cconflict model<jats:bold>,<\/jats:bold>\u201d where drug<jats:bold>\u2010<\/jats:bold>seeking and relapse encounter adverse consequences: an electrified grid in front of the drug\u2010delivering lever. Following behavioral testing, we explored a potential association between behavioral outcomes and protein expression of brain\u2010derived neurotrophic factor (BDNF). We found that DRL rats self\u2010administer more cocaine compared with both CMS and controls, while CMS and control groups did not differ significantly. Notably, DRL but not CMS rats, displayed higher rates of relapse than controls, and expressed higher levels of BDNF in the prelimbic cortex (PLC). Potential translation of these results suggest that medication\u2010resistant depressed patients tend to consume more drugs and are more susceptible to relapse. The increase in PLC BDNF levels is consistent with previous rat models of depression, and concomitantly<jats:bold>,<\/jats:bold> with its suggested role in promoting cocaine\u2010seeking.<\/jats:p>","DOI":"10.1111\/adb.12756","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T08:05:35Z","timestamp":1557216335000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Increased relapse to cocaine\u2010seeking in a genetic model for depression"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4650-766X","authenticated-orcid":false,"given":"Noga","family":"Zilkha","sequence":"first","affiliation":[{"name":"Department of Neurobiology Weizmann institute of Science  Rehovot Israel"},{"name":"Department of Life Sciences and the Zlotowski Center for Neuroscience Ben\u2010Gurion University  Be'er Sheva 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