ArticleBrain, behavior, and immunity2023
Chronic ethanol induces a pro-inflammatory switch in interleukin-1β regulation of GABAergic signaling in the medial prefrontal cortex of male mice.
Article in Brain, behavior, and immunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Gut-immune-PVAT axis is involved in ethanol-induced abdominal aortic dysfunction via IL-17RA, TLR4, and FPR1 signaling.Gut microbes · 2026Article
- Major depressive disorder-alcohol use disorder comorbidity: diagnosis, mechanisms and treatment.European archives of psychiatry and clinical neuroscience · 2026Review
- Astrocyte reactivity by alcohol dependence in the central amygdala.Brain, behavior, and immunity · 2026Article
- Alcohol drinking sex-dependently regulates interleukin-1 pro-inflammatory signaling in the prefrontal cortex of mice and rhesus macaques.Brain, behavior, and immunity · 2026Article
- A neuroimmune framework for understanding adolescent stress and risk of alcohol misuse.Brain, behavior, & immunity - health · 2026Review
- Translational evidence for increased central amygdala IL-6 activity in alcohol dependence.Journal of neuroinflammation · 2026Article
- EFFECTS OF TOLL-LIKE RECEPTOR 3 - DEPENDENT IMMUNE ACTIVATION IN MICE ARE SEX- AND TISSUE- SPECIFIC: IMPLICATIONS FOR ALCOHOL USE DISORDER.bioRxiv : the preprint server for biology · 2026Article
- Astrocyte Reactivity by Alcohol Dependence in the Central Amygdala.bioRxiv : the preprint server for biology · 2026Article
- Extensive genetic interactions (epistasis) linked to alcohol use disorder in a high-risk population.Communications biology · 2026Article
- Patch-Clamp Single-Cell Proteomics in Acute Brain Slices: A Framework for Recording, Retrieval, and Interpretation.ACS chemical neuroscience · 2026Article
- P2X7R Signaling and Differential Regulation of Neuroinflammatory and Behavior Responses in Male and Female Mice During Chronic Ethanol Exposure.International journal of molecular sciences · 2026Article
- Engaging Gut-to-Brain Signalling to Treat Alcohol Use Disorder.Addiction 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
- Integrative Genomics Approach Identifies Glial Transcriptomic Dysregulation and Risk in the Cortex of Individuals With Alcohol Use Disorder.Biological psychiatry · 2026Article
- Alcohol dependence-induced astrocyte immune activation in the nucleus accumbens.Neurobiology of disease · 2025Article
- Oxytocin significantly enhances GABAergic transmission in the central amygdala of alcohol-naïve and alcohol-dependent female rats.Neuropharmacology · 2025Article
- Sex differences in noradrenergic regulation of the medial prefrontal cortex in mice.Biology of sex differences · 2025Article
- Patch-Clamp Single-Cell Proteomics in Acute Brain Slices: A Framework for Recording, Retrieval, and Interpretation.bioRxiv : the preprint server for biology · 2025Article
- Article
- Novel neurotherapeutic targets for substance use disorders: Neuroplasticity, neuroinflammation, gasotransmitters and non-canonical organ systems.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
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Authors and funding
12 authors.
Funding
Abstract
Neuroimmune pathways regulate brain function to influence complex behavior and play a role in several neuropsychiatric diseases, including alcohol use disorder (AUD). In particular, the interleukin-1 (IL-1) system has emerged as a key regulator of the brain's response to ethanol (alcohol). Here we investigated the mechanisms underlying ethanol-induced neuroadaptation of IL-1β signaling at GABAergic synapses in the prelimbic region of the medial prefrontal cortex (mPFC), an area responsible for integrating contextual information to mediate conflicting motivational drives. We exposed C57BL/6J male mice to the chronic intermittent ethanol vapor-2 bottle choice paradigm (CIE-2BC) to induce ethanol dependence, and conducted ex vivo electrophysiology and molecular analyses. We found that the IL-1 system regulates basal mPFC function through its actions at inhibitory synapses on prelimbic layer 2/3 pyramidal neurons. IL-1β can selectively recruit either neuroprotective (PI3K/Akt) or pro-inflammatory (MyD88/p38 MAPK) mechanisms to produce opposing synaptic effects. In ethanol naïve conditions, there was a strong PI3K/Akt bias leading to a disinhibition of pyramidal neurons. Ethanol dependence produced opposite IL-1 effects - enhanced local inhibition via a switch in IL-1β signaling to the canonical pro-inflammatory MyD88 pathway. Ethanol dependence also increased cellular IL-1β in the mPFC, while decreasing expression of downstream effectors (Akt, p38 MAPK). Thus, IL-1β may represent a key neural substrate in ethanol-induced cortical dysfunction. As the IL-1 receptor antagonist (kineret) is already FDA-approved for other diseases, this work underscores the high therapeutic potential of IL-1 signaling/neuroimmune-based treatments for AUD.
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