Binge ethanol consumption can be attenuated by systemic administration of minocycline and is associated with enhanced neuroinflammation in the central amygdala.

Autor: Schrank S; Department of Psychology, USA., Sevigny JP; Department of Psychology, USA; Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, IL 60607, USA., Yunus NI; Department of Psychology, USA., Vetter KR; Department of Psychology, USA., Aguilar OD; Department of Psychology, USA., Ily V; Department of Psychology, USA., Valchinova M; Department of Psychology, USA., Keinath AT; Department of Psychology, USA; Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, IL 60607, USA., Sparta DR; Department of Psychology, USA; Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, IL 60607, USA. Electronic address: dsparta@uic.edu.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2025 Jan 01; Vol. 262, pp. 110174. Date of Electronic Publication: 2024 Oct 05.
DOI: 10.1016/j.neuropharm.2024.110174
Abstrakt: Alcohol use disorder (AUD) has a complicated pathophysiology. Binge ethanol intoxication may produce long-lasting changes throughout extended amygdala neurocircuitry including neuroinflammation, often leading to relapse. Therefore, understanding the role of binge drinking induced neuroinflammation on extended amygdala neurocircuitry is critically important for treatment. We sought to understand the role of neuroinflammation in a naturalized form of rodent binge ethanol drinking (Drinking in the Dark (DID)). In a 5-week DID paradigm, we demonstrate that acute intraperitoneal (IP) injection of the anti-inflammatory drug minocycline significantly reduced binge drinking repeatedly in male and female Cx3CR1-GFP and C57BL/6J mice. Importantly, IP administration transiently decreased intermittent access sucrose consumption, was not observed on the second IP injection, but did not significantly alter food or water consumption, suggesting that minocycline may produce initial acute aversive effects and may not alter long-term consumption of natural rewards. Examination of rodent behaviors post ethanol binge drinking reveals no lasting effects of minocycline treatment on locomotion or anxiety-like behavior. To assess neuroinflammation, we developed a novel analysis method using a Matlab image analysis script, which allows for non-biased skeletonization and evaluation of microglia morphology to determine a possible activation state in Cx3CR1-GFP knock-in mice after repeated DID. We observed significant morphological changes of microglia within the CeA, but no differences in the BLA. Taken together, this study demonstrates repeated binge ethanol consumption can produce significant levels of microglia morphology changes within the CeA, and that immunomodulatory therapies may be an intriguing pharmacological candidate for the treatment of AUD.
Competing Interests: Declaration of competing interest none.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
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