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Emerging work has shown that chronic exposure to lower doses of ethanol may lead to inflexible behaviors and promote aberrant reward seeking. This study investigated the impact of chronic, low\u2010dose ethanol exposure on neural substrates of reward and on motivated behavior.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adult C57BL\/6J mice were trained to self\u2010administer sucrose. Throughout training, mice received an injection of low\u2010dose ethanol (0.5\u2009g\/kg) or saline, 1\u2009h after each session. Mice did not receive ethanol during testing. Mice were then tested in a progressive ratio task where the reward magnitude of reinforcer was reduced (small or large) or increased (small or large). A subset of mice expressed a retrograde tracer in the nucleus accumbens (NAc), and cFos expression within NAc circuits was analyzed following a sucrose self\u2010administration session.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Chronic low\u2010dose ethanol exposure altered behavioral responding in female mice following small changes in reward magnitude. Female mice showed divergent response patterns when there was a small reduction in reward magnitude, with greater proportions of ethanol\u2010exposed female mice either increasing or decreasing responding versus controls. Following a small increase, low\u2010dose ethanol female mice significantly increased responding versus controls. Female\u2014but not male\u2014mice exposed to chronic low\u2010dose ethanol shifted behavioral strategy with a reduction in magazine \u201cchecking\u201d behavior. Low\u2010dose ethanol exposure altered cFos expression within the prelimbic cortex and its projections to the NAc during reward seeking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Chronic, low\u2010dose ethanol altered behavioral responding and strategy in female mice in response to changes in reward value. Low\u2010dose ethanol exposure impacted cFos induction in prelimbic cortex and its projections to NAc in both female and male mice. Future studies should investigate the consequences of chronic, low\u2010dose ethanol on brain and behavior to understand what underlying processes drive aberrant reward\u2010seeking behaviors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70264","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:00:23Z","timestamp":1772964023000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sex differences in low\u2010dose ethanol effects on motivated behavior and limbic corticostriatal activity in mice"],"prefix":"10.1111","volume":"50","author":[{"given":"Christina M.","family":"Curran\u2010Alfaro","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology Drexel University College of Medicine  Philadelphia Pennsylvania USA"},{"name":"Graduate Program in Neuroscience Drexel University College of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5084-0863","authenticated-orcid":false,"given":"Kathleen G.","family":"Bryant","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology Drexel University College of Medicine  Philadelphia Pennsylvania USA"},{"name":"Graduate Program in Neuroscience Drexel University College of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni\u2010Shae","family":"Ledgister","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology Drexel University College of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sana","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology Drexel University College of Medicine  Philadelphia Pennsylvania 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