ArticleAlcohol, clinical & experimental research2026
Impact of chronic alcohol and stress on midlife cognition and locus coeruleus integrity in mice.
Article in Alcohol, clinical & experimental research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Alcohol and Stress Together Can Lead to Long-Term, Dementia-Like Deleterious Effects in the Brain.Alcohol, clinical & experimental research · 2026Article
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Abstract
backgroundExcessive alcohol consumption and stress are associated with structural and functional alterations in the brain and impaired cognition. However, the persistence of long-term 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.
methodsC57BL/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 months of abstinence, mice were evaluated at midlife (11 months old) on volitional drinking and a final CIE/FSS challenge for stress-induced drinking. Spatial learning and cognitive flexibility were assessed using the Barnes maze before brains were collected to evaluate locus coeruleus (LC) integrity at 12 months old.
resultsCIE/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-related disorders, including elevated markers of oxidative stress, apoptosis, and reduced autoinhibitory function.
conclusionsOur findings highlight the long-lasting 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-lasting impacts of chronic alcohol and stress and how they may accelerate age-related cognitive decline.
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