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Clinical studies suggest that ketamine may be effective in AUD; however, preclinical findings have been inconclusive, likely due to varying rodent strains, intake protocols, and ketamine doses\/routes. This study investigated ketamine's effects on alcohol drinking in male and female Long Evans rats using multiple validated paradigms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In Experiments 1 and 2, rats underwent 4\u2009weeks of intermittent access two\u2010bottle choice (IA2BC) drinking. In Week 5, they received ketamine via intravenous infusion (0.0, 1.47, or 2.35\u2009mg\/kg) or intraperitoneal injection (0.0, 10, or 20\u2009mg\/kg) during acute withdrawal. Alcohol intake was monitored 24\u2009h posttreatment and for 3\u2009weeks to assess sustained effects. In Experiment 3, rats completed a modified drinking\u2010in\u2010the\u2010dark (DID) protocol for 2\u2009weeks, followed by 2\u2009weeks of forced abstinence. A single ketamine injection preceded re\u2010exposure to alcohol. In Experiment 4, rats were categorized as high or low drinkers after five DID\/abstinence cycles. During Cycle 6, six ketamine injections were administered. A final cycle assessed sustained effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In Experiments 1\u20133, ketamine had no significant acute or lasting effects on alcohol intake in either sex when given during acute withdrawal or following a single period of forced abstinence. In Experiment 4, moderate drinkers (low drinking females, high drinking males) showed reduced intake after the first postabstinence ketamine dose, but not to subsequent dosing. High drinking females responded to both initial and repeated treatments; however, effects did not persist after treatment cessation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ketamine's ability to reduce alcohol intake appears sex\u2010dependent, acute rather than sustained, and limited to high\u2010drinking females. These findings highlight the need to assess the safety of repeated or chronic ketamine use in AUD treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70275","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T03:22:56Z","timestamp":1773199376000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex and individual differences in ketamine's effects on alcohol drinking in rats"],"prefix":"10.1111","volume":"50","author":[{"given":"Sarah D.","family":"Jennings","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences College of Medicine, Florida State University  Tallahassee Florida USA"},{"name":"Program in Neuroscience College of Medicine, Florida State University  Tallahassee Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Yates","sequence":"additional","affiliation":[{"name":"Department of 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