ArticleBritish journal of pharmacology2012
Inhibiting the TLR4-MyD88 signalling cascade by genetic or pharmacological strategies reduces acute alcohol-induced sedation and motor impairment in mice.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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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.
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Who cites it
49 citing papers in PubMed, 76 citations in OpenAlex.
- Thiamine Deficiency and Neuroinflammation Are Important Contributors to Alcohol Use Disorder.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Review
- Low to moderate ethanol exposure reduces astrocyte-induced neuroinflammatory signaling and cognitive decline in presymptomatic APP/PS1 mice.Scientific reports · 2024Article
- Moderate ethanol exposure reduces astrocyte-induced neuroinflammatorysignaling and cognitive decline in presymptomatic APP/PS1 mice.Research square · 2023Article
- Effects of ethanol on mechanical allodynia and dynamic weight bearing in male and female mice with spared nerve injury.Alcohol, clinical & experimental research · 2023Article
- Sodium Butyrate Supplementation Modulates Neuroinflammatory Response Aggravated by Antibiotic Treatment in a Mouse Model of Binge-like Ethanol Drinking.International journal of molecular sciences · 2022Article
- Prenatal and adolescent alcohol exposure programs immunity across the lifespan: CNS-mediated regulation.Pharmacology, biochemistry, and behavior · 2022Review
- Review
- Immune treatments for alcohol use disorder: A translational framework.Brain, behavior, and immunity · 2021Review
- CRISPR Turbo Accelerated KnockOut (CRISPy TAKO) for RapidFrontiers in genome editing · 2020Article
- Toll-Like Receptor 4 Signaling and Drug Addiction.Frontiers in pharmacology · 2020Review
- Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala.Brain sciences · 2019Article
- Minocycline attenuates ethanol-induced cell death and microglial activation in the developing spinal cord.Alcohol (Fayetteville, N.Y.) · 2019Article
- Glial mechanisms underlying substance use disorders.The European journal of neuroscience · 2019Review
- Role of TLR4 in the Modulation of Central Amygdala GABA Transmission by CRF Following Restraint Stress.Alcohol and alcoholism (Oxford, Oxfordshire) · 2018Article
- The GABABrain sciences · 2018Article
- Innately activated TLR4 signal in the nucleus accumbens is sustained by CRF amplification loop and regulates impulsivity.Brain, behavior, and immunity · 2018Article
- Effects of gut-derived endotoxin on anxiety-like and repetitive behaviors in male and female mice.Biology of sex differences · 2018Article
- Peripheral TNFα elevations in abstinent alcoholics are associated with hepatitis C infection.PloS one · 2018Article
- Ethanol and Cytokines in the Central Nervous System.Handbook of experimental pharmacology · 2018Review
- Glial and neuroinflammatory targets for treating substance use disorders.Drug and alcohol dependence · 2017Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
background and purposeEmerging evidence implicates a role for toll-like receptor 4 (TLR4) in the CNS effects of alcohol. The aim of the current study was to determine whether TLR4-MyD88-dependent signalling is involved in the acute behavioural actions of alcohol and if alcohol can activate TLR4-downstream MAPK and NF-κB pathways. EXPERIMENTAL APPROACH: The TLR4 pathway was evaluated using the TLR4 antagonist (+)-naloxone (µ-opioid receptor-inactive isomer) and mice with null mutations in the TLR4 and MyD88 genes. Sedation and motor impairment induced by a single dose of alcohol were assessed by loss of righting reflex (LORR) and rotarod tests, separately. The phosphorylation of JNK, ERK and p38, and levels of IκBα were measured to determine the effects of acute alcohol exposure on MAPK and NF-κB signalling. KEY
resultsAfter a single dose of alcohol, both pharmacological inhibition of TLR4 signalling with (+)-naloxone and genetic deficiency of TLR4 or MyD88 significantly (P < 0.0001) reduced the duration of LORR by 45-78% and significantly decreased motor impairment recovery time to 62-88% of controls. These behavioural actions were not due to changes in the peripheral or central alcohol pharmacokinetics. IκBα levels responded to alcohol by 30 min in mixed hippocampal cell samples, from wild-type mice, but not in cells from TLR4- or MyD88-deficient mice. CONCLUSIONS AND IMPLICATIONS: These data provide new evidence that TLR4-MyD88 signalling is involved in the acute behavioural actions of alcohol in mice.
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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.