ArticleBrain, behavior, and immunity2019
Toll-like receptor 3 activation increases voluntary alcohol intake in C57BL/6J male mice.
Article in Brain, behavior, and immunity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 60 citations in OpenAlex.
- Alternative Polyadenylation in the Brain is Modulated by Chronic Ethanol Exposure in a Sex- and Cell Type-Specific Manner.Molecular neurobiology · 2026Article
- EFFECTS OF TOLL-LIKE RECEPTOR 3 - DEPENDENT IMMUNE ACTIVATION IN MICE ARE SEX- AND TISSUE- SPECIFIC: IMPLICATIONS FOR ALCOHOL USE DISORDER.bioRxiv : the preprint server for biology · 2026Article
- The need to incorporate polysubstance use in neuropsychopharmacology research: Biological lessons and new opportunities.Addiction neuroscience · 2026Article
- Ethanol exposure and high-fat diet: assessing the neuroimmune and metabolic mechanisms in Alzheimer's disease pathology.Frontiers in neuroscience · 2026Review
- Integrative Genomics Approach Identifies Glial Transcriptomic Dysregulation and Risk in the Cortex of Individuals With Alcohol Use Disorder.Biological psychiatry · 2026Article
- Late-Stage Activation of Toll-like receptor 3 Alleviates Cognitive Impairment and Neuropathology in an Alzheimer's Disease Mouse Model.Molecular neurobiology · 2025Article
- Dampened TLR2-mediated Inflammatory Signaling in Bats.Molecular biology and evolution · 2025Article
- Alcohol Use Disorder and the Gut-Brain Axis: A Narrative Review of the Role of Gut Microbiota and Implications for Treatment.Microorganisms · 2025Review
- Severe alcohol use and COVID-19: implications for physical and mental health.Frontiers in psychiatry · 2025Review
- Neuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats.Translational psychiatry · 2024Article
- Increased white blood cell in young adults with family histories of alcohol and other substance use disorders.Addiction biology · 2024Article
- Adolescent intermittent ethanol (AIE) sensitized fever in male Sprague Dawley rats exposed to poly I:C in adulthood.Brain, behavior, and immunity · 2024Article
- Toll-like receptor 7: A novel neuroimmune target to reduce excessive alcohol consumption.Neurobiology of stress · 2024Article
- From Immunity to Neurogenesis: Toll-like Receptors as Versatile Regulators in the Nervous System.International journal of molecular sciences · 2024Review
- Knockdown of Tlr3 in dorsal striatum reduces ethanol consumption and acute functional tolerance in male mice.Brain, behavior, and immunity · 2024Article
- Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Neuroimmune Activation and Microglia Reactivity in Female Rats Following Alcohol Dependence.International journal of molecular sciences · 2024Article
- Transcriptome changes in the nucleus of the solitary tract induced by repeated stress, alcohol dependence, or stress-induced drinking in dependent mice.Neuropharmacology · 2024Article
- Effects of repeated alcohol abstinence on within-subject prefrontal cortical gene expression in rhesus macaques.Advances in drug and alcohol research · 2024Article
- Sex-dependent factors of alcohol and neuroimmune mechanisms.Neurobiology of stress · 2023Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Many genes differentially expressed in brain tissue from human alcoholics and animals that have consumed large amounts of alcohol are components of the innate immune toll-like receptor (TLR) pathway. TLRs initiate inflammatory responses via two branches: (1) MyD88-dependent or (2) TRIF-dependent. All TLRs signal through MyD88 except TLR3. Prior work demonstrated a direct role for MyD88-dependent signaling in regulation of alcohol consumption. However, the role of TLR3 as a potential regulator of excessive alcohol drinking has not previously been investigated. To test the possibility TLR3 activation regulates alcohol consumption, we injected mice with the TLR3 agonist polyinosinic:polycytidylic acid (poly(I:C)) and tested alcohol consumption in an every-other-day two-bottle choice test. Poly(I:C) produced a persistent increase in alcohol intake that developed over several days. Repeated poly(I:C) and ethanol exposure altered innate immune transcript abundance; increased levels of TRIF-dependent pathway components correlated with increased alcohol consumption. Administration of poly(I:C) before exposure to alcohol did not alter alcohol intake, suggesting that poly(I:C) and ethanol must be present together to change drinking behavior. To determine which branch of TLR signaling mediates poly(I:C)-induced changes in drinking behavior, we tested either mice lacking MyD88 or mice administered a TLR3/dsRNA complex inhibitor. MyD88 null mutants showed poly(I:C)-induced increases in alcohol intake. In contrast, mice pretreated with a TLR3/dsRNA complex inhibitor reduced their alcohol intake, suggesting poly(I:C)-induced escalations in alcohol intake are, at least partially, dependent on TLR3. Together, these results strongly suggest that TLR3-dependent signaling drives excessive alcohol drinking behavior.
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Registered trials
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 OpenQuestion graph.