ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2008
Repeated lipopolysaccharide (LPS) or cytokine treatments sensitize ethanol withdrawal-induced anxiety-like behavior.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 62 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.
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.
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Who cites it
62 citing papers in PubMed, 109 citations in OpenAlex.
- Acute changes in immune biomarkers under low- and moderate-dose alcohol in light and heavy drinkers: A randomized, placebo-controlled trial.Alcohol, clinical & experimental research · 2025Trial
- Effects of ibudilast on central and peripheral markers of inflammation in alcohol use disorder: A randomized clinical trial.Addiction biology · 2022Trial
- Review
- Therapeutic Repurposing of Avanafil Against Lipopolysaccharide-induced Depression and Autoimmune Hepatitis: Gut-brain-liver Axis Orchestration Via Regulation of TLR4/NF-κB/IDO and Nrf2/HO-1 Pathways.Molecular neurobiology · 2026Article
- Microglia Promote Neurodegeneration and Hyperkatifeia during Withdrawal and Abstinence from Binge Alcohol.The American journal of pathology · 2026Article
- Microglia promote neurodegeneration and hyperkatifeia during withdrawal and prolonged abstinence from binge alcohol.bioRxiv : the preprint server for biology · 2025Article
- Age- and cytokine-dependent modulation of GABAergic transmission within the basolateral amygdala of male Sprague Dawley rats.Neuropharmacology · 2025Article
- Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit/Stress Surfeit Disorder.Current topics in behavioral neurosciences · 2025Review
- A reverse translational study of PPAR-α agonist efficacy in human and rodent models relevant to alcohol use disorder.Neurobiology of stress · 2024Article
- Alcohol and stress exposure across the lifespan are key risk factors for Alzheimer's Disease and cognitive decline.Neurobiology of stress · 2024Article
- NLRP3 deficiency decreases alcohol intake controlling anxiety-like behavior via modification of glutamatergic transmission in corticostriatal circuits.Journal of neuroinflammation · 2022Article
- Synaptic effects of IL-1β and CRF in the central amygdala after protracted alcohol abstinence in male rhesus macaques.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Covid-19 interface with drug misuse and substance use disorders.Neuropharmacology · 2021Review
- Immune treatments for alcohol use disorder: A translational framework.Brain, behavior, and immunity · 2021Review
- Increased Toll-like Receptor-MyD88-NFκB-Proinflammatory neuroimmune signaling in the orbitofrontal cortex of humans with alcohol use disorder.Alcoholism, clinical and experimental research · 2021Article
- Similarities in alcohol and opioid withdrawal syndromes suggest common negative reinforcement mechanisms involving the interoceptive antireward pathway.Neuroscience and biobehavioral reviews · 2021Review
- The Significance of Toll-Like Receptors in the Neuroimmunologic Background of Alcohol Dependence.Frontiers in psychiatry · 2021Review
- Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development.Pharmacological reviews · 2021Review
- Tumour Necrosis Factor in Neuroplasticity, Neurogenesis and Alcohol Use Disorder.Brain plasticity (Amsterdam, Netherlands) · 2020Review
- Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Previous investigations demonstrated that repeated stresses before an ethanol exposure sensitize ethanol withdrawal-induced anxiety-like behavior ('anxiety'). In addition to activating the hypothalamic-pituitary-adrenal axis, acute stress also elevates cytokines in brain. Initially, to test possible cytokine involvement in this stress/withdrawal protocol, cytokines were increased in brain with 2 weekly repeated lipopolysaccharide (LPS) administrations (1000 microg/kg) [corrected] (LPS/withdrawal protocol) or with twice weekly intracerebroventricular (i.c.v.) administrations of the cytokines IL-1 beta, CCL2 (MCP-1) or TNFalpha (cytokine/withdrawal protocol) before exposure and withdrawal from a 5-day cycle of chronic ethanol diet. Both protocols sensitized withdrawal-induced anxiety and confirm cytokine involvement in the sensitized anxiety response. Testing of various doses of LPS (16-1000 microg/kg) and TNFalpha (3-100 ng, i.c.v.) demonstrated the dose-related nature of these protocols to sensitize withdrawal-induced anxiety. The sensitized anxiety was not produced by a single 5-day ethanol diet cycle or by repeated LPS or cytokine treatments alone. Likewise, sensitized anxiety in these protocols could not be attributed to differences in ethanol ingestion. When challenged with a subsequent re-exposure to a 5-day ethanol diet cycle 16 days after completion of the LPS/withdrawal or cytokine/withdrawal protocols, an increase in withdrawal-induced anxiety was observed-an indication of induction of an underlying persistent adaptive change. Finally, just as found previously with the stress/withdrawal protocol, administration of the benzodiazepine receptor antagonist flumazenil before the LPS or TNF treatments prevented anxiety sensitization. Together, these findings indicate that increased cytokine activity induces adaptive change that supports sensitization of ethanol withdrawal-induced anxiety that may be linked to GABA(A)-receptor function.
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What OpenQuestion holds
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.