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Previous studies have demonstrated that drug\u2010seeking in rats progressively increases over time during withdrawal (incubation of drug craving). Here, we used male rats and examined neural mechanisms underlying incubation of craving to oxycodone, a commonly abused prescription opioid, and we focused on orbitofrontal cortex (OFC), a brain region previously implicated in incubation of heroin craving. We first used neuronal activity marker Fos and measured neuronal activation in OFC (ventral and lateral OFC) associated with day\u20101 and day\u201015 relapse tests. Next, we determined the effect of pharmacological reversible inactivation of OFC on incubated oxycodone seeking on withdrawal day 15. Finally, we determined the effect of reversible inactivation of OFC on nonincubated oxycodone seeking on withdrawal day 1. We found that lever presses during relapse tests were higher on withdrawal day 15 than on withdrawal day 1 (incubation of oxycodone craving). Incubation of oxycodone craving is accompanied with a time\u2010dependent increase of Fos protein expression in both ventral and lateral OFC. Lastly, OFC inactivation decreased oxycodone seeking on withdrawal day 15 but had no effect on withdrawal day 1. Together with the previous heroin study, results here show that OFC plays a critical role in incubation of opioid craving.<\/jats:p>","DOI":"10.1111\/adb.12927","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T22:04:20Z","timestamp":1592863460000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Role of orbitofrontal cortex in incubation of oxycodone craving in male rats"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1771-9287","authenticated-orcid":false,"given":"Rachel D.","family":"Altshuler","sequence":"first","affiliation":[{"name":"Department of Psychology University of Maryland College Park  College Park MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddy S.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Maryland College Park  College Park MD 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