Role of toll-like receptor 7 (TLR7) in voluntary alcohol consumption.
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
22
04
2020
revised:
09
07
2020
accepted:
22
07
2020
pubmed:
30
7
2020
medline:
28
4
2021
entrez:
30
7
2020
Statut:
ppublish
Résumé
Overactivation of neuroimmune signaling has been linked to excessive ethanol consumption. Toll-like receptors (TLRs) are a major component of innate immune signaling and initiate anti- and pro-inflammatory responses via intracellular signal transduction cascades. TLR7 is upregulated in post-mortem brain tissue from humans with alcohol use disorder (AUD) and animals with prior exposure to ethanol. Despite this evidence, the role of TLR7 in the regulation of voluntary ethanol consumption has not been studied. We test the hypothesis that TLR7 activation regulates voluntary ethanol drinking behavior by administering a TLR7 agonist (R848) during an intermittent access drinking procedure in mice. Acute activation of TLR7 reduced ethanol intake, preference, and total fluid intake due, at least in part, to an acute sickness response. However, chronic pre-treatment with R848 resulted in tolerance to the adverse effects of the drug and a subsequent increase in ethanol consumption. To determine the molecular machinery that mediates these behavioral changes, we evaluated gene expression after acute and chronic TLR7 activation. We found that acute TLR7 activation produces brain region specific changes in expression of immune pathway genes, whereas chronic TLR7 activation causes downregulation of TLRs and blunted cytokine induction, suggesting molecular tolerance. Our results demonstrate a novel role for TLR7 signaling in regulating voluntary ethanol consumption. Taken together, our findings suggest TLR7 may be a viable target for development of therapies to treat AUD.
Identifiants
pubmed: 32726684
pii: S0889-1591(20)30666-8
doi: 10.1016/j.bbi.2020.07.029
pmc: PMC7572874
mid: NIHMS1620107
pii:
doi:
Substances chimiques
Toll-Like Receptor 7
0
Toll-Like Receptors
0
Ethanol
3K9958V90M
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
423-432Subventions
Organisme : NIAAA NIH HHS
ID : R01 AA012404
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA013520
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA020926
Pays : United States
Organisme : NIAAA NIH HHS
ID : U24 AA025479
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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