Brain-wide functional architecture remodeling by alcohol dependence and abstinence
Open accessAbstract
Significance: Visualizing functional changes in brain networks that are produced by alcohol use and alcohol dependence is a critical step in our understanding of the consequences of drinking alcohol. Because of technical limitations, visualizing changes throughout the whole brain at single-cell resolution has not been possible. The present study used a single-cell whole-brain imaging approach in mice to assess whether alcohol abstinence alters functional architecture of the brain. Compared with nondrinkers and casual drinkers, alcohol-dependent mice exhibited widespread increases in coordinated brain activity during abstinence and a decrease in modularity. We also identified target brain regions for future research and provide a single-cell whole-brain atlas that may be used to better understand the consequences of alcohol use, dependence, and abstinence.
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Preclinical studies using the irritability-like paradigm reveal increased irritability-related responses during alcohol withdrawal.
“Preclinical studies using this paradigm reveal increased irritability-related responses during alcohol withdrawal, with evidence suggesting that such heightened reactivity can persist for at least two weeks into abstinence (Somkuwar et al. 2017; Kimbrough et al. 2020).”
From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Kimbrough et al. 2020
Heightened irritability-related reactivity during alcohol withdrawal can persist for at least two weeks into abstinence.
“Preclinical studies using this paradigm reveal increased irritability-related responses during alcohol withdrawal, with evidence suggesting that such heightened reactivity can persist for at least two weeks into abstinence (Somkuwar et al. 2017; Kimbrough et al. 2020).”
From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Kimbrough et al. 2020
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“We next assessed the way in which modular organization of the alcohol abstinence network was related to neurobiological organization of the brain that is proposed in the four major neurobiological theories that may explain excessive alcohol use in dependent subjects: recruitment of the mesolimbic dopamine system (58–6…”
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Russell, N. M., Frier, M. D., Bortolato, M., & Mangieri, R. A. (2026) · Psychopharmacology · doi:10.1007/s00213-025-06938-0 · Cited by 3 · see citing works
- Authors
- Kimbrough, A., Lurie, D. J., Collazo, A., Kreifeldt, M., Sidhu, H., Macedo, G. C., D’Esposito, M., Contet, C., & George, O.
- Affiliations
- University of California San Diego (US)
- University of California, Berkeley (US)
- Beckman Institute, California Institute of Technology, Pasadena, CA 91125;
- Scripps Research Institute (US)
- Corresponding author
- George, Olivier
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2020-01-14
- Volume
- 117
- Issue
- 4
- Pages
- 2149-2159
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6994986
- OpenAlex
- W3000490368
- Cited by
- 97
- References
- 12
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 12 · 2023: 18 · 2022: 18 · 2021: 16 · 2020: 5
- FWCI
- 7.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- HHS | NIH | National Institute on Alcohol Abuse and Alcoholism (AA006420, AA026081, AA022977, AA026685, AA024198, AA027301, AA007456)
- HHS | NIH | National Institute of Neurological Disorders and Stroke (NS079698)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- alcoholism, alcohol abstinence, brain functional architecture, network modularity, extended amygdala, striatum, neurocircuitry
- MeSH terms
- Alcohol Drinking, Amygdala, Animals, Brain, Disease Models, Animal, Humans, Male, Mice, Inbred C57BL, Mice, Alcohol Abstinence
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