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Although the pharmacology of fentanyl is well characterized, there is little information about the reinforcing effects of clandestine fentanyl analogs (FAs).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objectives<\/jats:title>\n                <jats:p>Here, we compared the effects of fentanyl and the FAs acetylfentanyl, butyrylfentanyl, and cyclopropylfentanyl on drug self-administration in male and female rats. These FAs feature chemical modifications at the carbonyl moiety of the fentanyl scaffold.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Sprague-Dawley rats fitted with intravenous jugular catheters were placed in chambers containing two nose poke holes. Active nose poke responses resulted in drug delivery (0.2 mL) over 2\u00a0s on a fixed-ratio 1 schedule, followed by a 20\u00a0s timeout. Acquisition doses were 0.01\u00a0mg\/kg\/inj for fentanyl and cyclopropylfentanyl, and 0.03\u00a0mg\/kg\/inj for acetylfentanyl and butyrylfentanyl. After 10 days of acquisition, dose-effect testing was carried out, followed by 10 days of saline extinction.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Self-administration of fentanyl and FAs was acquired by both male and female rats, with no sex differences in acquisition rate. Fentanyl and FAs showed partial inverted-U dose-effect functions; cyclopropylfentanyl and fentanyl had similar potency, while acetylfentanyl and butyrylfentanyl were less potent. Maximal response rates were similar across drugs, with fentanyl and cyclopropylfentanyl showing maximum responding at 0.001\u00a0mg\/kg\/inj, acetylfentanyl at 0.01\u00a0mg\/kg\/inj, and butyrylfentanyl at 0.003\u00a0mg\/kg\/inj. No sex differences were detected for drug potency, efficacy, or rates of extinction.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our work provides new evidence that FAs display significant abuse liability in male and female rats, which suggests the potential for compulsive use in humans.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00213-024-06641-6","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T03:33:53Z","timestamp":1720150433000},"page":"2375-2383","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Reinforcing effects of fentanyl analogs found in illicit drug markets"],"prefix":"10.1007","volume":"241","author":[{"given":"Alexander D.","family":"Maitland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby A.","family":"McGriff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant C.","family":"Glatfelter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles W.","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7758-1470","authenticated-orcid":false,"given":"Michael H.","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"6641_CR1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.neuropharm.2017.10.016","volume":"134","author":"P Armenian","year":"2018","unstructured":"Armenian P, Vo KT, Barr-Walker J, Lynch KL (2018) Fentanyl, fentanyl analogs and novel synthetic opioids: a comprehensive review. 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