ArticleAlcohol and alcoholism (Oxford, Oxfordshire)2016
Evaluation of TLR4 Inhibitor, T5342126, in Modulation of Ethanol-Drinking Behavior in Alcohol-Dependent Mice.
Article in Alcohol and alcoholism (Oxford, Oxfordshire), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 36 citations in OpenAlex.
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- IL-10 normalizes aberrant amygdala GABA transmission and reverses anxiety-like behavior and dependence-induced escalation of alcohol intake.Progress in neurobiology · 2021Article
- Microglia Control Escalation of Drinking in Alcohol-Dependent Mice: Genomic and Synaptic Drivers.Biological psychiatry · 2020Article
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- Driving the Downward Spiral: Alcohol-Induced Dysregulation of Extended Amygdala Circuits and Negative Affect.Alcoholism, clinical and experimental research · 2019Review
- Systemic Administration of the Cyclin-Dependent Kinase Inhibitor (S)-CR8 Selectively Reduces Escalated Ethanol Intake in Dependent Rats.Alcoholism, clinical and experimental research · 2019Article
- Glial mechanisms underlying substance use disorders.The European journal of neuroscience · 2019Review
- Function and Mechanism of Myelin Regulation in Alcohol Abuse and Alcoholism.BioEssays : news and reviews in molecular, cellular and developmental biology · 2019Review
- Neuroimmune signaling in alcohol use disorder.Pharmacology, biochemistry, and behavior · 2019Review
- IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala.Brain, behavior, and immunity · 2019Article
- Ethanol Exposure Induces Microglia Activation and Neuroinflammation through TLR4 Activation and SENP6 Modulation in the Adolescent Rat Hippocampus.Neural plasticity · 2019Article
- Role of TLR4 in the Modulation of Central Amygdala GABA Transmission by CRF Following Restraint Stress.Alcohol and alcoholism (Oxford, Oxfordshire) · 2018Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
aimsSeveral lines of evidence support a critical role of TLR4 in the neuroimmune responses associated with alcohol disorders and propose inhibitors of TLR4 signaling as potential treatments for alcoholism. In this work, we investigated the effect of T5342126 compound, a selective TLR4 inhibitor, on excessive drinking and microglial activation associated with ethanol dependence.
methodsWe used 2BC-CIE (two-bottle choice-chronic ethanol intermittent vapor exposure) paradigm to induce ethanol dependence in mice. After induction of the ethanol dependence, we injected T5342126 (i.p., 57 mg/kg) for 14 days while monitoring ethanol intake by 2BC (limited access to ethanol) method.
resultsT5342126 decreased ethanol drinking in both ethanol-dependent and non-dependent mice but T5342126 showed also dose-dependent non-specific effects represented by decreased animal locomotor activity, saccharine intake, and body core temperature. Six days after the last ethanol-drinking session, we examined the immunohistochemical staining of Iba-1 (ionized calcium-binding adapter molecule 1), a microglial activation marker, in the central nucleus of the amygdala (CeA) and dentate gyrus (DG) of the hippocampus. Notably, T5342126 reduced Iba-1 density in the CeA of both ethanol-dependent and non-dependent mice injected with T5342126. There were no significant differences in the DG Iba-1 density among the treatment groups.
conclusionsCollectively, our data suggest that T5342126, via blocking TLR4 activation, contributes to the reduction of ethanol drinking and ethanol-induced neuroimmune responses. However, the non-specific effects of T5342126 may play a significant role in the T5342126 effects on ethanol drinking and thus, may limit its therapeutic potential for treatment of alcohol dependence. SHORT SUMMARY: T5342126, an experimental TLR4 inhibitor, is effective in reducing ethanol drinking and inhibiting the activation and proliferation of microglia in both ethanol-dependent and non-dependent mice. However, T5342126's use as a potential candidate for the treatment of alcohol addiction may be limited due to its non-specific effects.
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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.