Evidence map›Paper›PMID 41833757›Full record

ArticleBrain, behavior, and immunity2026

Alcohol drinking sex-dependently regulates interleukin-1 pro-inflammatory signaling in the prefrontal cortex of mice and rhesus macaques.

Andrea Liss, Clara C Lowe, Mahum T Siddiqi, Dhruba Podder, Marcis V Scroger, Gianna Vessey, Kenna Martin, Noah M Paperny, David M Lam, Allison E Martin and 11 more

Abstract read
In one paragraph

Article in Brain, behavior, and immunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Andrea LissDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
Clara C LoweDepartment of Translational Neuroscience, Wake Forest University, School of Medicine, Winston-Salem, NC, USA.
Mahum T SiddiqiDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
Dhruba PodderDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
Marcis V ScrogerDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
Gianna VesseyDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
Kenna MartinDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
Noah M PapernyDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
David M LamDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University-State University of New York, Binghamton, NY, USA.
Allison E MartinDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University-State University of New York, Binghamton, NY, USA.
Jariel N BacarDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
Katie T VoDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
Amy AstefanousDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
Nolawit BelachewDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
Eghosa IdahorDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
April T DavenportDepartment of Translational Neuroscience, Wake Forest University, School of Medicine, Winston-Salem, NC, USA.
James B DaunaisCenter for Precision Medicine, Wake Forest University, School of Medicine, Winston-Salem, NC, USA; Department of Internal Medicine, Section of Infectious Diseases, Wake Forest University, School of Medicine, Winston-Salem, NC, USA.
William M HayesDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA.
Rita Cervera-JuanesDepartment of Translational Neuroscience, Wake Forest University, School of Medicine, Winston-Salem, NC, USA; Center for Precision Medicine, Wake Forest University, School of Medicine, Winston-Salem, NC, USA.
Tony D DavisDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University-State University of New York, Binghamton, NY, USA.
Florence P VarodayanDepartment of Psychology, Binghamton University-State University of New York, Binghamton, NY, USA. Electronic address: fvaroday@binghamton.edu.

Funding

Social Anxiety, Stress and Ethanol Sensitivity in Adolescence and AdulthoodP50AA017823 · NIAAA · UPSTATE MEDICAL UNIVERSITY · PI Marvin Rafael Diaz · 2009 to 2026
$30.5M
Monkey Alcohol Tissue Research Resource (MATRR)R24AA019431 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI Mary Lauren Benton, Verginia Carmella Cuzon Carlson · 2010 to 2026
$10.3M
MULTI-DISCIPLINARY TRAINING IN THE BIOLOGY OF ALCOHOLISMT32AA007565 · NIAAA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI BRIAN A MCCOOL · 1994 to 2026
$10.1M
Early Stress & Alcoholism: Neurobiological AnalysisU01AA014106 · NIAAA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI FRIEDMAN, DAVID P · 2003 to 2011
$3.4M
Distinguishing preexistent and induced epigenetic risk for alcohol use disordersR01AA026278 · NIAAA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI CERVERA JUANES, RITA P · 2019 to 2023
$3.2M
Development and Neuroadaptations in Alcohol and Addictions (DNA2)T32AA025606 · NIAAA · STATE UNIVERSITY OF NY,BINGHAMTON · PI J. DAVID JENTSCH · 2017 to 2026
$2.7M
Identifying new targets for the treatment of alcohol dependence and relapse: epigenetic analysis of the abstinent brainR01AA027552 · NIAAA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI CERVERA JUANES, RITA P · 2020 to 2024
$2.6M
Profiling the alcohol-naive primate cortex to understand the functional role of epigenetics in predisposing the brain to risky alcohol useR01AA032162 · NIAAA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Rita P Cervera Juanes, Kip D Zimmerman · 2025 to 2026
$1.3M
Interrogation of Microbial Natural Product MethyltransferasesR00GM129454 · NIGMS · STATE UNIVERSITY OF NY,BINGHAMTON · PI DAVIS, TONY D. · 2021 to 2023
$747k
Neuroimmune mechanisms of adult chronic ethanol consumptionR21AA031101 · NIAAA · STATE UNIVERSITY OF NY,BINGHAMTON · PI VARODAYAN, FLORENCE PRABHA · 2023 to 2023
$405k
NIAAA NIH HHS P50 AA017823NIAAA NIH HHS R01 AA026278NIAAA NIH HHS R01 AA027552NIAAA NIH HHS R01 AA032162NIAAA NIH HHS R21 AA031101NIAAA NIH HHS R24 AA019431NIAAA NIH HHS T32 AA007565NIAAA NIH HHS T32 AA025606NIAAA NIH HHS U01 AA014106NIGMS NIH HHS R00 GM129454
6 · The paper itself

Abstract

Alcohol use disorder (AUD) causes executive dysfunction, leading to reduced treatment adherence, worse clinical outcomes, and relapse. Current medications do not address these symptoms. Targeting the neuroimmune interleukin-1 (IL-1) system has potential, but its mechanistic role in prefrontal cortex (PFC) dysfunction is unclear. Here we investigated how chronic alcohol consumption shifts IL-1 regulation of the rodent and non-human primate PFC. We found that alcohol drinking decreased reference memory and shifted the search strategy in mice of both sexes, and this deficit correlated with altered IL-1 receptor accessory protein (IL-1RAcP) mRNA levels in the medial PFC (mPFC) of male mice. Notably, the IL-1 system triggers either neuroprotective or proinflammatory cascades depending on the IL-1RAcP isoform recruited to the IL-1 receptor 1 complex. Alcohol drinking sex-dependently shifted mPFC IL-1RAcP gene expression (increased neuroprotective IL-1RAcP mRNA in female mice) and IL-1 regulation of mPFC synapses (increased GABA transmission that was specifically prevented by pharmacological blockade of the proinflammatory IL-1RAcP pathway in male mice) to support resilience in females vs. susceptibility in males. Notably, female alcohol-drinking rhesus macaques showed a similar increase in dorsolateral PFC (dlPFC) neuroprotective IL-1RAcP mRNA, with no change in males. Therefore, IL-1RAcP is a key AUD neural substrate that may sex-dependently switch the dl/mPFC from engaging in neuroprotective to proinflammatory synaptic mechanisms. This type of signaling bias is a recent focus of rational drug development and supports development of novel AUD pharmacotherapeutics based on biased IL-1 signaling, particularly for men.

Indexed as

Alcohol DrinkingInterleukin-1Prefrontal CortexAlcoholismAnimalsEthanolFemaleInflammationInterleukin-1 Receptor Accessory ProteinMacaca mulattaMaleMiceMice, Inbred C57BLReceptors, Interleukin-1Sex FactorsSignal TransductionEthanolInterleukin-1Interleukin-1 Receptor Accessory ProteinReceptors, Interleukin-1Cognitive behaviorEthanolGABAinterleukin-1 beta, IL-1βNon-human primateprefrontal cortex, PFCSynaptic transmission

Identifiers

PMID41833757
PMCPMC13322405

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.