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

Alcohol Drinking / genetics Animals Cytokines / metabolism Ethanol / administration & dosage Male Mice Mice, Inbred C57BL Myeloid Differentiation Factor 88 / metabolism Poly I-C / pharmacology Sex Factors Signal Transduction / drug effects Toll-Like Receptor 3 / metabolism Toll-Like Receptor 4 / metabolism
Alcohol use disorder Cytokines Drinking Ethanol Neuroimmune Poly(I:C) Toll-like receptors

Journal

Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478

Informations de publication

Date de publication:
03 2019
Historique:
received: 28 07 2018
revised: 21 11 2018
accepted: 10 12 2018
pubmed: 15 12 2018
medline: 26 2 2020
entrez: 15 12 2018
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.bbi.2018.12.004 PMID: 30550931 PMC: PMC6399060
pubmed: 30550931
pii: S0889-1591(18)30386-6
doi: 10.1016/j.bbi.2018.12.004
pmc: PMC6399060
mid: NIHMS1518473
pii:
doi:

Substances chimiques

Cytokines 0
Myd88 protein, mouse 0
Myeloid Differentiation Factor 88 0
TLR3 protein, mouse 0
Tlr4 protein, mouse 0
Toll-Like Receptor 3 0
Toll-Like Receptor 4 0
Ethanol 3K9958V90M
Poly I-C O84C90HH2L

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

55-65

Subventions

Organisme : NIAAA NIH HHS
ID : P01 AA020683
Pays : United States
Organisme : NIAAA NIH HHS
ID : F31 AA025499
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA020926
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA012404
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA006399
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA013520
Pays : United States

Informations de copyright

Copyright © 2018 Elsevier Inc. All rights reserved.

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Auteurs

Anna S Warden (AS)

Waggoner 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 Azzam (M)

Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.

Adriana DaCosta (A)

Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.

Sonia Mason (S)

Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.

Yuri A Blednov (YA)

Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.

Robert O Messing (RO)

Waggoner 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 Mayfield (RD)

Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.

R Adron Harris (RA)

Waggoner 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.

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Classifications MeSH

questionsmedicales.fr › Comportement et mécanismes comportementaux › Comportement › Comportement dipsique › Consommation d'alcool › Toll-like receptor 3 activation increases...
questionsmedicales.fr › Eucaryotes › Animaux › Toll-like receptor 3 activation increases...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Toll-like receptor 3 activation increases...
questionsmedicales.fr › Composés chimiques organiques › Alcools › Éthanol › Toll-like receptor 3 activation increases...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Toll-like receptor 3 activation increases...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Toll-like receptor 3 activation increases...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Facteur de différenciation myéloïde-88 › Toll-like receptor 3 activation increases...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Polynucléotides › Polyribonucléotides › Poly I › Poly I-C › Toll-like receptor 3 activation increases...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Facteurs épidémiologiques › Facteurs sexuels › Toll-like receptor 3 activation increases...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Toll-like receptor 3 activation increases...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs de reconnaissance de motifs moléculaires › Récepteurs de type Toll › Récepteur de type Toll-3 › Toll-like receptor 3 activation increases...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs de reconnaissance de motifs moléculaires › Récepteurs de type Toll › Récepteur de type Toll-4 › Toll-like receptor 3 activation increases...