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However, although discriminative stimulus effects of carfentanil in rats had been reported, its abuse potential has not been fully evaluated. In this study, we evaluated the abuse potential of carfentanil via the tests of conditioned place preference (CPP), drug self\u2010administration and naloxone\u2010precipitated opioid withdrawal assay, compared with fentanyl and heroin. Carfentanil exhibited significant place preference at a minimum dose of 1\u00a0\u03bcg\/kg in mice, whereas fentanyl and heroin induced significant place preference at the minimum doses of 100\u2009\u03bcg\/kg and 1000\u2009\u03bcg\/kg, respectively. In the drug\u2010substitution test in heroin self\u2010administered rats (50\u2009\u03bcg\/kg\/infusion), carfentanil and fentanyl acquired significant self\u2010administrations above saline levels from 0.05\u20130.1 and 0.1\u201310.0\u00a0\u03bcg\/kg\/infusion, respectively. Carfentanil induced the maximum number of infusions at 0.1\u00a0\u03bcg\/kg, whereas fentanyl and heroin at 1 and 25\u2009\u03bcg\/kg, respectively. In short, carfentanil showed the highest potency to induce CPP and self\u2010administration. Furthermore, repeated treatment with escalating doses of carfentanil, fentanyl or heroin induced typical withdrawal symptoms in mice, including a greater number of jumping and weight loss than saline group. This indicated that carfentanil could produce physical dependence similar to fentanyl and heroin. Taken together, the present study demonstrated the higher abuse potential of carfentanil compared with fentanyl and heroin. The rank order of abuse potential for these compounds is carfentanil\u2009&gt;\u2009fentanyl\u2009&gt;\u2009heroin.<\/jats:p>","DOI":"10.1111\/adb.13265","type":"journal-article","created":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T02:58:56Z","timestamp":1673060336000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Assessment of abuse potential of carfentanil"],"prefix":"10.1111","volume":"28","author":[{"given":"Jiayun","family":"Wei","sequence":"first","affiliation":[{"name":"School of Pharmacy China Pharmaceutical University  Nanjing China"},{"name":"Office of China National Narcotics Control Commission China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control  Beijing China"},{"name":"Zhejiang Xiaoshan Hospital  Hangzhou 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