{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:31:17Z","timestamp":1785526277541,"version":"3.56.0"},"reference-count":64,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["U01AA025481"],"award-info":[{"award-number":["U01AA025481"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Excessive alcohol consumption and stress are associated with structural and functional alterations in the brain and impaired cognition. However, the persistence of long\u2010term neural impacts after alcohol and stress is less understood. This study investigated midlife cognition and neuropathological changes following a history of alcohol and stress exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>C57BL\/6J mice acclimated to ethanol drinking (15% v\/v) before exposure to four cycles of alternating chronic intermittent ethanol (CIE) vapor exposure and repeated forced swim stress (FSS), with control groups exposed to air and no stress (AIR\/NS). After 3\u2009months of abstinence, mice were evaluated at midlife (11\u2009months old) on volitional drinking and a final CIE\/FSS challenge for stress\u2010induced drinking. Spatial learning and cognitive flexibility were assessed using the Barnes maze before brains were collected to evaluate locus coeruleus (LC) integrity at 12\u2009months old.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CIE\/FSS increased volitional alcohol intake, and this drinking phenotype persisted through to midlife despite extended abstinence. CIE\/FSS mice showed intact spatial learning but impaired flexibility in the Barnes maze reversal phase. Flexibility impairments were driven by decreased time in the target quadrant and increased errors during the reversal test compared with AIR\/NS. Furthermore, CIE\/FSS mice showed pathological measures of reduced LC integrity common to dementia\u2010related disorders, including elevated markers of oxidative stress, apoptosis, and reduced autoinhibitory function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings highlight the long\u2010lasting impact of alcohol and stress exposure on cognition, with flexibility impairments persisting into midlife. In addition to cognitive changes, alcohol and stress history produced pathological changes in the LC, an area known to mediate cognitive flexibility via its forebrain projections. Together, these results give insight into the long\u2010lasting impacts of chronic alcohol and stress and how they may accelerate age\u2010related cognitive decline.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70273","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T01:20:56Z","timestamp":1773105656000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of chronic alcohol and stress on midlife cognition and locus coeruleus integrity in mice"],"prefix":"10.1111","volume":"50","author":[{"given":"O.","family":"Revka","sequence":"first","affiliation":[{"name":"Department of Biology University of Massachusetts Amherst  Amherst Massachusetts USA"},{"name":"Neuroscience and Behavior Program University of Massachusetts Amherst  Amherst Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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