Evidence map›Paper›PMID 35470561›Full record

ArticleAddiction biology2022

The Toll-like receptor 7 agonist imiquimod increases ethanol self-administration and induces expression of Toll-like receptor related genes.

Dennis F Lovelock, Wen Liu, Sarah E Langston, Jiaqi Liu, Kalynn Van Voorhies, Kaitlin A Giffin, Ryan P Vetreno, Fulton T Crews, Joyce Besheer

Open access · hybridAbstract read
In one paragraph

Article in Addiction biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

23 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
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  4. Review
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  9. Nutrients · 2025
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Alcohol, HMGB1, and Innate Immune Signaling in the Brain.Alcohol research : current reviews · 2024
    Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. 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

9 authors at 1 institution in 1 country.

Dennis F LovelockBowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Wen LiuBowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Sarah E LangstonBowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Jiaqi LiuBowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Kalynn Van VoorhiesBowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Kaitlin A GiffinBowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Ryan P VetrenoBowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.ORCID 0000-0003-0449-395X
Fulton T CrewsBowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Joyce BesheerBowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.ORCID 0000-0001-6187-8376
University of North Carolina at Chapel Hill · US

Funding

UNC ARC Information/Dissemination CoreP60AA011605 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Clyde W Hodge · 2003 to 2026
$46.3M
Supplement to Molecular and Cellular Studies on Alcohol's ActionsT32AA007573 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FULTON T CREWS, Thomas L. Kash · 1997 to 2026
$9.3M
UNC-CH NADIA Underage Drinking and Adult Brain Morphology in RatsU01AA020023 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CREWS, FULTON T · 2010 to 2024
$7.5M
UNC-CH NADIA Administrative CoreU24AA020024 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CREWS, FULTON T · 2010 to 2024
$6.6M
MOLECULAR AND CELLULAR PATHOGENESIS IN ALCOHOLISMP50AA011605 · NIAAA · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI OVERSTREET, DAVID H · 1998 to 2002
$4.9M
Pregnane X receptor (PRX)-dependent mechanisms of alcoholic liver diseaseU54AA019767 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CREWS, FULTON T · 2010 to 2019
$2.1M
Adolescent Alcohol in 5xFAD Mouse Model Accelerates Neuroinflammation and Alzheimer's Disease Pathology Across AgingR01AG072894 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI VETRENO, RYAN PETER · 2020 to 2024
$1.9M
Long Island University- Brooklyn MBRS- RISE ProgramR25GM089568 · NIGMS · LONG ISLAND UNIVERSITY BROOKLYN CAMPUS · PI DEPASS, ANTHONY LYNDON · 2010 to 2013
$1.3M
HMGB1 and innate immune involvement in adult neuropathology following adolescent alcohol exposureK01AA025713 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI VETRENO, RYAN PETER · 2018 to 2022
$826k
Interoceptive processing and alcohol relapse-like behaviorF32AA029289 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LOVELOCK, DENNIS · 2021 to 2021
$73k
NIAAA NIH HHS F32 AA029289NIAAA NIH HHS K01 AA025713NIAAA NIH HHS P50 AA011605NIAAA NIH HHS P60 AA011605NIAAA NIH HHS T32 AA007573NIAAA NIH HHS U01 AA020023NIAAA NIH HHS U24 AA020024NIAAA NIH HHS U54 AA019767NIA NIH HHS R01 AG072894NIGMS NIH HHS R25 GM089568
6 · The paper itself

Abstract

There is growing evidence that immune signalling may be involved in both the causes and consequences of alcohol abuse. Toll-like receptor (TLR) expression is increased by alcohol consumption and is implicated in AUD, and specifically TLR7 may play an important role in ethanol consumption. We administered the TLR7-specific agonist imiquimod in male and female Long-Evans rats to determine (1) gene expression changes in brain regions involved in alcohol reinforcement, the nucleus accumbens core and anterior insular cortex, in rats with and without an alcohol history, and (2) whether TLR7 activation could modulate operant alcohol self-administration. Interferon regulatory factor 7 (IRF7) was dramatically increased in both sexes at both 2- and 24-h post-injection regardless of alcohol history and TLR3 and 7 gene expression was increased as well. The proinflammatory cytokine TNFα was increased 24-h post-injection in rats with an alcohol self-administration history, but this effect did not persist after four injections, suggesting molecular tolerance. Ethanol consumption was increased 24 h after imiquimod injections but did not occur until the third injection, suggesting adaptation to repeated TLR7 activation is necessary for increased drinking to occur. Notably, imiquimod reliably induced weight loss, indicating that sickness behaviour persisted across repeated injections. These findings show that TLR7 activation can modulate alcohol drinking in an operant self-administration paradigm and suggest that TLR7 and IRF7 signalling pathways may be a viable druggable target for treatment of AUD.

Indexed as

EthanolToll-Like Receptor 7AnimalsConditioning, OperantFemaleImiquimodMaleRatsRats, Long-EvansToll-Like ReceptorsEthanolImiquimodToll-Like Receptor 7Toll-Like ReceptorsalcoholAUDimiquimodIRF7self-administrationTLR7

Identifiers

PMID35470561
PMCPMC9286850
OpenAlexW4224279791

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.