Translational evidence for increased central amygdala IL-6 activity in alcohol dependence

Authors

• Celsey M. St Onge, The Scripps Research Institute, La Jolla, CA
• Chloe Erikson, The Scripps Research Institute, La Jolla, CA
• Bryan Cruz, The Scripps Research Institute, La Jolla, CA
• Vittoria Borgonetti, The Scripps Research Institute, La Jolla, CA
• Joel G. Hashimoto, Oregon Health & Science University, Portland, OR
• Jessica A. Cucinello-Ragland, LSU Health Sciences Center - New Orleans
• Taylor Fitzpatrick-Schmidt, LSU Health Sciences Center - New OrleansFollow
• Larry Rodriguez, The Scripps Research Institute, La Jolla, CA
• Sophia Khom, The Scripps Research Institute, La Jolla, CA
• Michela Palmisano, The Scripps Research Institute, La Jolla, CA
• Roman Vlkolinsky, The Scripps Research Institute, La Jolla, CA
• Christopher S. Oleata, The Scripps Research Institute, La Jolla, CA
• Tali Nadav, The Scripps Research Institute, La Jolla, CA
• Nihal A. Salem, University of Texas at Austin, Austin, TX
• Scott Edwards, LSU Health Sciences Center - New OrleansFollow
• R Dayne Mayfield, University of Texas at Austin, Austin, TX
• Marina Guizzetti, Oregon Health & Science University, Portland, OR
• Amanda J. Roberts, The Scripps Research Institute, La Jolla, CA
• Michal Bajo, The Scripps Research Institute, La Jolla, CA
• Marisa Roberto, The Scripps Research Institute, La Jolla, CA

Document Type

Article

Publication Date

5-22-2026

Publication Title

Journal of Neuroinflammation

Abstract

Alcohol use disorder (AUD) is one of the most prevalent mental health disorders worldwide yet effective therapeutics remain limited. Mounting evidence indicates that dysregulated immune signaling in the brain plays a role in AUD pathophysiology. Activation of pro-inflammatory pathways like the interleukin-6 (IL-6) pathway represents a potential point of convergence between synaptic dysfunction and motivational changes in AUD that remain undiscovered. Thus, using a translational neuroscience approach and well-established model of chronic alcohol intake, we investigated the cell-type specific role of IL-6 signaling in the central amygdala, a critical region in the development and maintenance of alcohol dependence. We demonstrate that chronic alcohol exposure recruits IL-6-related pathways in humans and rodents via astrocytic, neuronal, and microglial mechanisms, and that IL-6 inhibits central amygdala GABAergic transmission. Notably, systemic administration of an IL-6 receptor antibody decreased alcohol drinking in alcohol-dependent female mice. Collectively, our findings support IL-6 inhibition as a novel-neuroimmune-targeted therapeutic strategy to reduce excessive drinking in the context of AUD.

First Page

1

Last Page

23

PubMed ID

42174622

Volume

23

Issue

1

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

St Onge, Celsey M.; Erikson, Chloe; Cruz, Bryan; Borgonetti, Vittoria; Hashimoto, Joel G.; Cucinello-Ragland, Jessica A.; Fitzpatrick-Schmidt, Taylor; Rodriguez, Larry; Khom, Sophia; Palmisano, Michela; Vlkolinsky, Roman; Oleata, Christopher S.; Nadav, Tali; Salem, Nihal A.; Edwards, Scott; Mayfield, R Dayne; Guizzetti, Marina; Roberts, Amanda J.; Bajo, Michal; and Roberto, Marisa, "Translational evidence for increased central amygdala IL-6 activity in alcohol dependence" (2026). School of Medicine Faculty Publications. 4843.
https://digitalscholar.lsuhsc.edu/som_facpubs/4843
10.1186/s12974-026-03868-2