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Mitragynine (MG) is the most abundant alkaloid found in kratom.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The present studies evaluated whether MG decreases methamphetamine self-administration under both fixed-ratio (FR) and progressive-ratio (PR) schedules. In a separate cohort we examined whether MG would alter food-maintained responding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Three separate experiments were conducted in male and female adult Sprague\u2013Dawley rats. In Experiment 1, rats self-administered methamphetamine (0.032\u00a0mg\/kg\/infusion, intravenous) under a fixed-ratio (FR) schedule. In Experiment 2, a separate group received food pellets under a FR schedule. In Experiment 3, a different group received methamphetamine (0.032\u00a0mg\/kg\/infusion) under a progressive-ratio (PR) schedule. In all experiments rats received pretreatment with MG (10\u201356\u00a0mg\/kg, intraperitoneal) or vehicle 30\u00a0min before testing. Behavioral measures included active and inactive lever presses, response rates, and in the case of PR, breakpoints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MG dose-dependently reduced methamphetamine delivery under both the FR and PR schedules, with significant decreases in active lever presses, and breakpoints at 32 and 56\u00a0mg\/kg. Effects were generally comparable in males and females, without significant sex\u2009\u00d7\u2009treatment interaction detected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MG decreased methamphetamine-maintained responding at doses that did not affect food-maintained responding, indicating a selective effect on methamphetamine reinforcement relative to natural reward. These findings identify MG as a compound with robust effects on methamphetamine-maintained behavior and support its continued evaluation in preclinical models of methamphetamine use disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00213-026-07124-6","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T08:30:39Z","timestamp":1783672239000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitragynine reduces methamphetamine self-administration in rats without disrupting food-maintained responding"],"prefix":"10.1007","author":[{"given":"Lida","family":"Khodavirdilou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio D Zuarth","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushobhan","family":"Mukhopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Guadagnoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Obeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"McCurdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance R.","family":"McMahon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5594-061X","authenticated-orcid":false,"given":"Jenny L.","family":"Wilkerson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"7124_CR1","doi-asserted-by":"publisher","first-page":"222","DOI":"10.3390\/ph18020222","volume":"18","author":"AS Alford","year":"2025","unstructured":"Alford AS, Moreno HL, Benjamin MM et al (2025) Exploring the therapeutic potential of mitragynine and corynoxeine: kratom-derived indole and oxindole alkaloids for pain management. 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