ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2017
Genetic and Pharmacologic Manipulation of TLR4 Has Minimal Impact on Ethanol Consumption in Rodents.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 81 citations in OpenAlex.
- Astrocyte reactivity by alcohol dependence in the central amygdala.Brain, behavior, and immunity · 2026Article
- Review
- Astrocyte Reactivity by Alcohol Dependence in the Central Amygdala.bioRxiv : the preprint server for biology · 2026Article
- Chronic alcohol consumption sex-dependently affects IL-6 modulation of GABAergic synapses in the central amygdala of rhesus macaques.Brain, behavior, and immunity · 2026Article
- Cannabidiol mitigates alcohol dependence and withdrawal with neuroprotective effects in the basolateral amygdala and striatum.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Central amygdala neuroimmune signaling in alcohol use disorder.Addiction neuroscience · 2025Article
- The link between early-life adversity and later alcohol use disorder: A role for microglia?Neurobiology of stress · 2025Article
- Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit/Stress Surfeit Disorder.Current topics in behavioral neurosciences · 2025Review
- Neuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats.Translational psychiatry · 2024Article
- Toll-like receptor 7: A novel neuroimmune target to reduce excessive alcohol consumption.Neurobiology of stress · 2024Article
- Sex-dependent factors of alcohol and neuroimmune mechanisms.Neurobiology of stress · 2023Article
- The effects of lipopolysaccharide exposure on social interaction, cytokine expression, and alcohol consumption in male and female mice.Physiology & behavior · 2023Article
- Review
- The neuroimmune system - Where aging and excess alcohol intersect.Alcohol (Fayetteville, N.Y.) · 2023Review
- Animal model for high consumption and preference of ethanol and its interplay with high sugar and butter diet, behavior, and neuroimmune system.Frontiers in nutrition · 2023Article
- Regulation of alcohol drinking by ventral striatum and extended amygdala circuitry.Neuropharmacology · 2022Review
- Circulating corticosterone levels mediate the relationship between acute ethanol intoxication and markers of NF-κB activation in male rats.Neuropharmacology · 2022Article
- The Toll-like receptor 7 agonist imiquimod increases ethanol self-administration and induces expression of Toll-like receptor related genes.Addiction biology · 2022Article
- Prenatal and adolescent alcohol exposure programs immunity across the lifespan: CNS-mediated regulation.Pharmacology, biochemistry, and behavior · 2022Review
- Adolescent neuroimmune function and its interaction with alcohol.International review of neurobiology · 2022Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
Abstract
Toll-like receptor 4 (TLR4) is a critical component of innate immune signaling and has been implicated in alcohol responses in preclinical and clinical models. Members of the Integrative Neuroscience Initiative on Alcoholism (INIA-Neuroimmune) consortium tested the hypothesis that TLR4 mediates excessive ethanol drinking using the following models: (1) Tlr4 knock-out (KO) rats, (2) selective knockdown of Tlr4 mRNA in mouse nucleus accumbens (NAc), and (3) injection of the TLR4 antagonist (+)-naloxone in mice. Lipopolysaccharide (LPS) decreased food/water intake and body weight in ethanol-naive and ethanol-trained wild-type (WT), but not Tlr4 KO rats. There were no consistent genotypic differences in two-bottle choice chronic ethanol intake or operant self-administration in rats before or after dependence. In mice, (+)-naloxone did not decrease drinking-in-the-dark and only modestly inhibited dependence-driven consumption at the highest dose. Tlr4 knockdown in mouse NAc did not decrease drinking in the two-bottle choice continuous or intermittent access tests. However, the latency to ethanol-induced loss of righting reflex increased and the duration decreased in KO versus WT rats. In rat central amygdala neurons, deletion of Tlr4 altered GABA SIGNIFICANCE STATEMENT: Toll-like receptor 4 (TLR4) is a key mediator of innate immune signaling and has been implicated in alcohol responses in animal models and human alcoholics. Members of the Integrative Neuroscience Initiative on Alcoholism (INIA-Neuroimmune) consortium participated in the first comprehensive study across multiple laboratories to test the hypothesis that TLR4 regulates excessive alcohol consumption in different species and different models of chronic, dependence-driven, and binge-like drinking. Although TLR4 was not a critical determinant of excessive drinking, it was important in the acute sedative effects of alcohol. Current research efforts are directed at determining which neuroimmune pathways mediate excessive alcohol drinking and these findings will help to prioritize relevant pathways and potential therapeutic targets.
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