Evidence map›Paper›PMID 41421735›Full record

ArticleBrain, behavior, and immunity2026

Chronic alcohol consumption sex-dependently affects IL-6 modulation of GABAergic synapses in the central amygdala of rhesus macaques.

Michal Bajo, Pauravi Gandhi, Suzanne S Fei, Yun Yu, Lina Gao, Rupak Khadka, Madison B Blanton, Ilhem Messaoudi, Anna S Warden, R Dayne Mayfield and 3 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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Astrocyte Reactivity by Alcohol Dependence in the Central Amygdala.bioRxiv : the preprint server for biology · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Michal BajoDepartment of Translational Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Pauravi GandhiDepartment of Translational Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Suzanne S FeiBiostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Bioinformatics & Biostatistics Core, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
Yun YuBiostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Bioinformatics & Biostatistics Core, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
Lina GaoBiostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Bioinformatics & Biostatistics Core, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
Rupak KhadkaDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
Madison B BlantonPharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA.
Ilhem MessaoudiMicrobiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY, USA.
Anna S WardenDepartment of Neuroscience and Waggoner Center for Alcohol and Addiction Research (WCAAR), University of Texas at Austin, Austin, TX, USA.
R Dayne MayfieldDepartment of Neuroscience and Waggoner Center for Alcohol and Addiction Research (WCAAR), University of Texas at Austin, Austin, TX, USA.
Verginia C Cuzon CarlsonDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
Kathleen A GrantDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA. Electronic address: grantka@ohsu.edu.
Marisa RobertoDepartment of Translational Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
Viral Vector CoreP60AA006420 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI AMANDA J ROBERTS · 2003 to 2026
$46.3M
Translational measures of risk for excessive alcohol consumptionP60AA010760 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI TAMARA J. PHILLIPS · 2006 to 2026
$34.5M
Electrophysiology of alcohol in extended amygdelaU01AA013498 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI MARISA ROBERTO · 2001 to 2026
$12.6M
Stress and Ethanol Self-Administration in MonkeysU01AA013510 · NIAAA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI KATHLEEN A GRANT · 2002 to 2026
$11.8M
GENE EXPRESSION IN THE HUMAN ALCOHOLIC BRAINR01AA012404 · NIAAA · UNIVERSITY OF TEXAS AUSTIN · PI MAYFIELD, ROY DAYNE · 2000 to 2025
$10.7M
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
Next Generation Sequencing of Human Alcoholic BrainU01AA020926 · NIAAA · UNIVERSITY OF TEXAS AT AUSTIN · PI Roy DAYNE MAYFIELD · 2011 to 2026
$6.7M
Impact of chronic ethanol consumption on lung functional and immunological landscape and implication for susceptibility to SARSCoV2 infectionR01AA028735 · NIAAA · UNIVERSITY OF KENTUCKY · PI MESSAOUDI, ILHEM, VARLAMOV, OLEG · 2020 to 2025
$4.4M
Gene-environment interaction: the brain CRF system in alcohol preferring msP ratsR37AA017447 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI ROBERTO, MARISA · 2016 to 2025
$3.7M
INIA: Stress, Anxiety and Excessive Alcohol Drinking (Administrative Core)U24AA013641 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI KATHLEEN A GRANT · 2016 to 2026
$3.4M
Neuroimmune mechanisms in stress and alcohol comorbidityR01AA027700 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI ROBERTO, MARISA · 2019 to 2023
$2.4M
NIAAA NIH HHS F31 AA031600NIAAA NIH HHS P60 AA006420NIAAA NIH HHS P60 AA010760NIAAA NIH HHS R01 AA012404NIAAA NIH HHS R01 AA017447NIAAA NIH HHS R01 AA027700NIAAA NIH HHS R01 AA028735NIAAA NIH HHS R01 AA029841NIAAA NIH HHS R24 AA019431NIAAA NIH HHS R37 AA017447NIAAA NIH HHS U01 AA013498NIAAA NIH HHS U01 AA013510NIAAA NIH HHS U01 AA020926NIAAA NIH HHS U24 AA013641NIH HHS P51 OD011092
6 · The paper itself

Abstract

The implications of the neuroimmune system in the pathogenesis of alcohol use disorders (AUD) have been undeniable. Understanding how chronic alcohol dysregulates inflammatory pathways in the brain leading to altered neuronal functions could provide insight into specific mechanisms and neuroadaptations that may contribute to drinking behaviors. For example, the neuroadaptations at inhibitory GABAergic synapses in the central nucleus of the amygdala (CeA) of rodents and macaques involve the recruitment of neuroimmune pathways. This study tested the hypothesis that chronic alcohol consumption dysregulates the pro-inflammatory cytokine, interleukin 6 (IL-6) in the CeA of rhesus macaques. Male and female rhesus macaques were provided continuous choice to drink either 4 % (w/v) ethanol or water for 22 h/day, every day, for more than one year. We assessed the impact of chronic ethanol drinking on the cytokine abundance, including IL-6, in the blood, and adaptive changes in the CeA GABAergic transmission and transcriptome. We observed a main effect of sex on the IL-6 circulating plasma levels at necropsy, with higher IL-6 plasma levels in females, but no main effect of ethanol nor an interaction between sex and ethanol drinking. IL-6 decreased CeA GABA release (sIPSC frequency) in both control and alcohol drinkers, however chronic ethanol drinking significantly potentiated the IL-6 effects in both sexes. While, IL-6 had no effects on the sIPSC amplitudes in the control group, we observed a main effect of ethanol drinking on IL-6-induced decrease of sIPSC amplitude in both male and female drinkers. IL-6 also significantly prolonged the kinetics (decay times) of sIPSCs in male controls and drinkers, but not in the females, regardless of drinking. These data suggest that IL-6 modulation of GABAergic transmission within the CeA via a presynaptic reduction in GABA release independent of sex, whereas postsynaptic GABA receptor mediated functions (sIPSC amplitude and decay time) show sex- and ethanol specific effects. Lastly, transcriptomic analysis of the IL-6-immune-related genes in the CeA between high and low ethanol drinkers identified several DEGs (differentially expressed genes) implicating the neural and glial processes, and extracellular matrix as a generalized inflammatory response to ethanol in the high drinkers.

Indexed as

Alcohol DrinkingCentral Amygdaloid NucleusGABAergic NeuronsInterleukin-6AlcoholismAmygdalaAnimalsEthanolFemalegamma-Aminobutyric AcidMacaca mulattaMaleSex FactorsSynapsesEthanolgamma-Aminobutyric AcidInterleukin-6BrainCytokineElectrophysiologyEthanolGene expressionNon-human primatesRNA-seqSynaptic transmission

Identifiers

PMID41421735
PMCPMC12969976

What Socratic holds

Textmetadata
LicenceTDM
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.