Southard Meg T, Giannotti Giuseppe, Thakar Amit, Willsey Trinity R, Bailey Lydia G, Salazar Frank, Hentges Shane, Quock Raymond M, Brown Travis E
Department of Integrative Physiology and Neuroscience, Washington State University, 1815 Ferdinand's Lane, Pullman, WA, 99163, USA.
Department of Psychology, Washington State University, 1505 NE Stadium Way, Pullman, WA, 99164, USA.
Sci Rep. 2025 Jul 2;15(1):23677. doi: 10.1038/s41598-025-07937-z.
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.
阿片类药物使用障碍带来了一个复杂的挑战,其特点是复发率高,这源于身体依赖和心理脆弱性之间的复杂相互作用。先前的研究表明,高压氧治疗(HBOT),即在高压下暴露于100%氧气,可减轻吗啡依赖雄性小鼠的身体戒断症状。然而,HBOT对雌性小鼠的影响、其对与吗啡暴露相关的奖赏和厌恶行为的影响,以及可能驱动这些影响的潜在机制仍不清楚。我们证实了HBOT在减轻雄性小鼠身体戒断症状方面的有益作用,并且首次证明HBOT也能减轻雌性小鼠的这些症状。HBOT对吗啡条件性位置偏爱或条件性位置厌恶没有显著影响,这表明我们的HBOT方案不会影响动机行为。最后,我们表明HBOT治疗可减少吗啡处理的雄性和雌性小鼠室旁核中的小胶质体细胞体体积,这表明HBOT后向“静息”状态转变。这些发现共同表明,HBOT可能提供一种有前景且非药物性的方法来减轻两性的阿片类药物戒断症状,可能是通过调节小胶质细胞来实现的。