Evidence map›Paper›PMID 30550931›Full record

ArticleBrain, behavior, and immunity2019

Toll-like receptor 3 activation increases voluntary alcohol intake in C57BL/6J male mice.

Anna S Warden, Moatasem Azzam, Adriana DaCosta, Sonia Mason, Yuri A Blednov, Robert O Messing, R Dayne Mayfield, R Adron Harris

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
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

50 citing papers in PubMed, 60 citations in OpenAlex.

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  7. Dampened TLR2-mediated Inflammatory Signaling in Bats.Molecular biology and evolution · 2025
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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

8 authors at 1 institution in 1 country.

Anna S WardenWaggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA; Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA. Electronic address: wardena@utexas.edu.
Moatasem AzzamWaggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.
Adriana DaCostaWaggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.
Sonia MasonWaggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.
Yuri A BlednovWaggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.
Robert O MessingWaggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA; Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA; Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA.
R Dayne MayfieldWaggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.
R Adron HarrisWaggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA; Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA.
The University of Texas at Austin · US

Funding

GENE EXPRESSION IN THE HUMAN ALCOHOLIC BRAINR01AA012404 · NIAAA · UNIVERSITY OF TEXAS AUSTIN · PI MAYFIELD, ROY DAYNE · 2000 to 2025
$10.7M
INIA: ANIMAL COREU01AA013520 · NIAAA · UNIVERSITY OF TEXAS AUSTIN · PI YURI A BLEDNOV, ROBERT O. MESSING · 2001 to 2026
$9.5M
BRAIN MEMBRANES IN ALCOHOL AND BENZODIAZEPINE DEPENDENCER01AA006399 · NIAAA · UNIVERSITY OF TEXAS AUSTIN · PI HARRIS, ROBERT A · 1985 to 2018
$8.8M
Next Generation Sequencing of Human Alcoholic BrainU01AA020926 · NIAAA · UNIVERSITY OF TEXAS AT AUSTIN · PI Roy DAYNE MAYFIELD · 2011 to 2026
$6.7M
Novel molecular and cellular approaches for alcoholism medication developmentP01AA020683 · NIAAA · UNIVERSITY OF TEXAS AT AUSTIN · PI MIHIC, S JOHN · 2012 to 2016
$3.3M
Molecular investigations of the TRIF-dependent pathway in alcohol abuseF31AA025499 · NIAAA · UNIVERSITY OF TEXAS AT AUSTIN · PI WARDEN, ANNA · 2016 to 2019
$111k
BRAIN MEMBRANES IN ALCOHOL AND BENZODIAZEPINE DEPENDENCER37AA006399 · NIAAA · UNIVERSITY OF TEXAS AUSTIN · PI HARRIS, ROBERT ADRON · 1989 to 1998
–
NIAAA NIH HHS F31 AA025499NIAAA NIH HHS P01 AA020683NIAAA NIH HHS R01 AA006399NIAAA NIH HHS R01 AA012404NIAAA NIH HHS R37 AA006399NIAAA NIH HHS U01 AA013520NIAAA NIH HHS U01 AA020926
6 · The paper itself

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.

Indexed as

Alcohol DrinkingAnimalsCytokinesEthanolMaleMiceMice, Inbred C57BLMyeloid Differentiation Factor 88Poly I-CSignal TransductionToll-Like Receptor 3Toll-Like Receptor 4CytokinesEthanolMyd88 protein, mouseMyeloid Differentiation Factor 88Poly I-CTLR3 protein, mouseTlr4 protein, mouseToll-Like Receptor 3Toll-Like Receptor 4Alcohol use disorderCytokinesDrinkingEthanolNeuroimmunePoly(I:C)Toll-like receptors

Identifiers

PMID30550931
PMCPMC6399060
OpenAlexW2951902842

What OpenQuestion 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 OpenQuestion graph.