Hyperbaric oxygen treatment attenuates naloxone-precipitated opioid withdrawal behaviors and alters microglial activity in male and female mice

Abstract Opioid use disorder poses a complex challenge marked by high relapse rates, which stem from an intricate interplay between physical dependence and psychological vulnerabilities. Previous research has demonstrated that hyperbaric oxygen treatment (HBOT), exposure to 100% oxygen under elevate...

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Main Authors: Meg T. Southard, Giuseppe Giannotti, Amit Thakar, Trinity R. Willsey, Lydia G. Bailey, Frank Salazar, Shane Hentges, Raymond M. Quock, Travis E. Brown
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-07937-z
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author Meg T. Southard
Giuseppe Giannotti
Amit Thakar
Trinity R. Willsey
Lydia G. Bailey
Frank Salazar
Shane Hentges
Raymond M. Quock
Travis E. Brown
author_facet Meg T. Southard
Giuseppe Giannotti
Amit Thakar
Trinity R. Willsey
Lydia G. Bailey
Frank Salazar
Shane Hentges
Raymond M. Quock
Travis E. Brown
author_sort Meg T. Southard
collection DOAJ
description Abstract Opioid use disorder poses a complex challenge marked by high relapse rates, which stem from an intricate interplay between physical dependence and psychological vulnerabilities. Previous research has demonstrated that hyperbaric oxygen treatment (HBOT), exposure to 100% oxygen under elevated pressure, reduced physical withdrawal symptoms in morphine-dependent male mice. However, remaining unknown are the effects of HBOT in female mice, its impact on the rewarding and aversive behaviors associated with morphine exposure, and the underlying mechanisms that may be driving these effects. We confirmed the beneficial effects of HBOT in reducing physical withdrawal signs in male mice and, for the first time, demonstrated that HBOT also alleviates these symptoms in female mice. HBOT had no significant effect on morphine-conditioned place preference or conditioned place aversion, suggesting that our HBOT regimen does not influence motivated behaviors. Finally, we show that HBOT treatment reduces microglial soma volume in morphine-treated male and female mice in the paraventricular thalamus, suggesting a shift towards a “resting” state after HBOT. These findings collectively suggest that HBOT may offer a promising, non-pharmacological approach to mitigating opioid withdrawal symptoms across sexes, potentially through modulation of microglia.
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spelling doaj-art-601c273ed38149f39ccc5dc084a84d562025-08-20T04:01:24ZengNature PortfolioScientific Reports2045-23222025-07-0115111610.1038/s41598-025-07937-zHyperbaric oxygen treatment attenuates naloxone-precipitated opioid withdrawal behaviors and alters microglial activity in male and female miceMeg T. Southard0Giuseppe Giannotti1Amit Thakar2Trinity R. Willsey3Lydia G. Bailey4Frank Salazar5Shane Hentges6Raymond M. Quock7Travis E. Brown8Department of Integrative Physiology and Neuroscience, Washington State UniversityDepartment of Integrative Physiology and Neuroscience, Washington State UniversityDepartment of Integrative Physiology and Neuroscience, Washington State UniversityDepartment of Psychology, Washington State UniversityDepartment of Integrative Physiology and Neuroscience, Washington State UniversityDepartment of Integrative Physiology and Neuroscience, Washington State UniversityDepartment of Integrative Physiology and Neuroscience, Washington State UniversityDepartment of Psychology, Washington State UniversityDepartment of Integrative Physiology and Neuroscience, Washington State UniversityAbstract Opioid use disorder poses a complex challenge marked by high relapse rates, which stem from an intricate interplay between physical dependence and psychological vulnerabilities. Previous research has demonstrated that hyperbaric oxygen treatment (HBOT), exposure to 100% oxygen under elevated pressure, reduced physical withdrawal symptoms in morphine-dependent male mice. However, remaining unknown are the effects of HBOT in female mice, its impact on the rewarding and aversive behaviors associated with morphine exposure, and the underlying mechanisms that may be driving these effects. We confirmed the beneficial effects of HBOT in reducing physical withdrawal signs in male mice and, for the first time, demonstrated that HBOT also alleviates these symptoms in female mice. HBOT had no significant effect on morphine-conditioned place preference or conditioned place aversion, suggesting that our HBOT regimen does not influence motivated behaviors. Finally, we show that HBOT treatment reduces microglial soma volume in morphine-treated male and female mice in the paraventricular thalamus, suggesting a shift towards a “resting” state after HBOT. These findings collectively suggest that HBOT may offer a promising, non-pharmacological approach to mitigating opioid withdrawal symptoms across sexes, potentially through modulation of microglia.https://doi.org/10.1038/s41598-025-07937-z
spellingShingle Meg T. Southard
Giuseppe Giannotti
Amit Thakar
Trinity R. Willsey
Lydia G. Bailey
Frank Salazar
Shane Hentges
Raymond M. Quock
Travis E. Brown
Hyperbaric oxygen treatment attenuates naloxone-precipitated opioid withdrawal behaviors and alters microglial activity in male and female mice
Scientific Reports
title Hyperbaric oxygen treatment attenuates naloxone-precipitated opioid withdrawal behaviors and alters microglial activity in male and female mice
title_full Hyperbaric oxygen treatment attenuates naloxone-precipitated opioid withdrawal behaviors and alters microglial activity in male and female mice
title_fullStr Hyperbaric oxygen treatment attenuates naloxone-precipitated opioid withdrawal behaviors and alters microglial activity in male and female mice
title_full_unstemmed Hyperbaric oxygen treatment attenuates naloxone-precipitated opioid withdrawal behaviors and alters microglial activity in male and female mice
title_short Hyperbaric oxygen treatment attenuates naloxone-precipitated opioid withdrawal behaviors and alters microglial activity in male and female mice
title_sort hyperbaric oxygen treatment attenuates naloxone precipitated opioid withdrawal behaviors and alters microglial activity in male and female mice
url https://doi.org/10.1038/s41598-025-07937-z
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