New Brain Study Explains How Binge Drinking Contributes to Long-Lasting Negative Feelings

New research has identified that neuroinflammation driven by microglia (immune cells in the brain) is a primary underlying driver of prolonged negative feelings caused by repeated, sustained binge drinking (binge exposure). Negative emotional states caused by alcohol contribute to alcohol use disorder (AUD) and its associated mental health conditions such as depression. The findings from a study in The American Journal of Pathology, published by Elsevier, open the door for immune therapies to treat AUD, for which effective treatments are currently limited.

The natural history of AUD involves stressful life experiences followed by the initiation of binge drinking episodes. These experiences interact with more proximal stressors fueling alcohol-seeking behavior, with stress, caused by repeated cycles of binge alcohol use and withdrawal synergizing with lifetime stressors, that brings on hyperkatifeia, an intense state of negative emotions.

Previous research has shown that neuroinflammation, particularly proinflammatory microglia, is a pathologic feature of AUD. However, whether microglia contribute directly to the development of negative emotions with heavy alcohol use has not been determined. Since neuroinflammation can alter mood in other settings, the researchers thought microglia might contribute to negative emotional states that are caused by chronic alcohol.

Researchers used mouse models to test the long-lasting impact of alcohol on emotional state. Mice received either short (4 days) or longer (10 days) exposure to binge alcohol, and emotional state (anxiety-like behavior and fear memory) were assessed during abstinence. In other groups of mice microglia were inhibited using a targeted genetic method during alcohol exposure, and their emotional state and level of neuronal death were assessed.

The investigators found that longer alcohol exposure, but not shorter alcohol exposure (10 days vs 4 days in this model), led to brain damage and negative emotional states because the brain's microglia were activated, leading to long-lasting neuroinflammation. Preventing proinflammatory microglia activation during 10 days of alcohol exposure blocked the alcohol-induced neuronal death and prevented the development of anxiety during withdrawal and persistent fear memory during abstinence.

Lead investigator Leon G. Coleman, Jr., MD, PhD, University of North Carolina at Chapel Hill School of Medicine, Department of Pharmacology and Bowles Center for Alcohol Studies, explains, “Our findings underscore that repeated bouts of heavy drinking induce neuroinflammation, perpetuating a vicious cycle that locks individuals into chronic negative emotions. These biological consequences emphasize the critical need to avoid heavy drinking.”

Nearly 95 million individuals worldwide experience AUD, which is characterized by difficulty in ceasing alcohol use despite adverse effects on health and/or social life. Current treatments for AUD include pharmacotherapies (naltrexone, acamprosate, and disulfiram), behavioral interventions, and support groups. Despite these options, approximately 60% of individuals with AUD relapse within the first year after treatment.

There are currently no medications that target hyperkatifeia caused by alcohol misuse. These negative emotions not only contribute to risk for AUD but are also associated with other psychiatric disorders.

Dr. Coleman concludes, “We were a little surprised at how dramatic the protection was. The fact that immune cells in the brain were found to be so important for neuronal dysfunction indicates that targeting these microglia to interrupt the cycle of negative feelings could be a promising treatment strategy for alcohol-related mood disorders.”

Notes for editors

The article is “Microglia Promote Neurodegeneration and Hyperkatifeia during Withdrawal and Abstinence from Binge Alcohol,” by Elizabeth M. McNair, Lamar W. Dawkins, Baylee Materia, Grace Ross, Alexandra Barnett, Puja Nakkala, Liya Qin, Jian Zou, Viktoriya Nikolova, Sheryl Moy, and Leon G. Coleman, Jr. (https://doi.org/10.1016/j.ajpath.2025.10.005). It appears in The American Journal of Pathology, volume 196, issue 1 (January 2026), published by Elsevier.

The article is openly available at https://ajp.amjpathol.org/article/S0002-9440(25)00404-3/fulltext.

Full text of the article is also available to credentialed journalists upon request. Contact Eileen Leahy at +1 732 406 1313 or [email protected] to request a PDF of the article or more information. To reach the study’s authors, contact Leon G. Coleman, Jr., MD, PhD, at [email protected].

This study was supported by the National Institutes of Health (grants AA024829, AA028924, AA031414, AA011605, AA030463, and P50HD103573); and the Bowles Center for Alcohol Studies.

About The American Journal of Pathology

The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches. ajp.amjpathol.org

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