Pro-inflammatory microglia drive escalated alcohol consumption during early abstinence
Abstract
Despite growing evidence that neuroimmune dysfunction contributes to Alcohol Use Disorder (AUD) pathology, the underlying neuroinflammatory mechanisms that may promote alcohol consumption are not as clear. We recently report that specific knockdown of interferon regulatory factor 7 (IRF7) in the anterior insula (aIC) mitigates escalation in ethanol self-administration in rats. In addition, we find pro-inflammatory activation of microglia contributes to other AUD-related behavioral impairments. Here, we sought to determine if pro-inflammatory activation of microglia from ethanol contributes to elevations in IRF7 and ethanol self-administration in rats. Male Wistar rats were trained under our ethanol self-administration paradigm (15% v/v; FR2 vs inactive lever) followed by 1-4 cycles of chronic intermittent ethanol vapor exposure (CIE). To inhibit microglia, rats were treated with minocycline (30mg/kg, i.p.) before and after each ethanol vapor session. Escalation in self-administration and biochemical markers were assessed 72 hours into abstinence. We found CIE increased ethanol self-administration, which was positively correlated with aIC IRF7 levels. Minocycline treatment blunted IRF7 expression and alleviated ethanol self-administration following CIE. LC-MS/MS proteomics of primary microglia from the aIC of rats following CIE with and without minocycline treatment indicate minocycline promotes metabolic and ribosomal re-wiring of microglia during early abstinence. These data suggest a role for microglia in driving both IRF7 levels and escalation in ethanol self-administration in early abstinence.
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BibTeX
@misc{anton2026proinflammatory,
title = {{Pro-inflammatory microglia drive escalated alcohol consumption during early abstinence}},
author = {P. E. Anton and B. M. Materia and D. Lovelock and S. McDonald and S. Lyons and A. Mordant and L. E. Herring and J. Besheer and L. G. Coleman},
howpublished = {bioRxiv},
year = {2026},
month = jul,
doi = {10.64898/2026.07.30.741570},
url = {https://www.biorxiv.org/content/10.64898/2026.07.30.741570v2},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Pro-inflammatory microglia drive escalated alcohol consumption during early abstinence
AU - P. E. Anton
AU - B. M. Materia
AU - D. Lovelock
AU - S. McDonald
AU - S. Lyons
AU - A. Mordant
AU - L. E. Herring
AU - J. Besheer
AU - L. G. Coleman
PY - 2026
DA - 2026/07/30
PB - bioRxiv
DO - 10.64898/2026.07.30.741570
UR - https://www.biorxiv.org/content/10.64898/2026.07.30.741570v2
AB - Despite growing evidence that neuroimmune dysfunction contributes to Alcohol Use Disorder (AUD) pathology, the underlying neuroinflammatory mechanisms that may promote alcohol consumption are not as clear. We recently report that specific knockdown of interferon regulatory factor 7 (IRF7) in the anterior insula (aIC) mitigates escalation in ethanol self-administration in rats. In addition, we find pro-inflammatory activation of microglia contributes to other AUD-related behavioral impairments. Here, we sought to determine if pro-inflammatory activation of microglia from ethanol contributes to elevations in IRF7 and ethanol self-administration in rats. Male Wistar rats were trained under our ethanol self-administration paradigm (15% v/v; FR2 vs inactive lever) followed by 1-4 cycles of chronic intermittent ethanol vapor exposure (CIE). To inhibit microglia, rats were treated with minocycline (30mg/kg, i.p.) before and after each ethanol vapor session. Escalation in self-administration and biochemical markers were assessed 72 hours into abstinence. We found CIE increased ethanol self-administration, which was positively correlated with aIC IRF7 levels. Minocycline treatment blunted IRF7 expression and alleviated ethanol self-administration following CIE. LC-MS/MS proteomics of primary microglia from the aIC of rats following CIE with and without minocycline treatment indicate minocycline promotes metabolic and ribosomal re-wiring of microglia during early abstinence. These data suggest a role for microglia in driving both IRF7 levels and escalation in ethanol self-administration in early abstinence.
ER -