Chronic Physical and Vicarious Psychosocial Stress Alter Fentanyl Consumption and Nucleus Accumbens Rho GTPases in Male and Female C57BL/6 Mice.

Chronic Physical and Vicarious Psychosocial Stress Alter Fentanyl Consumption and Nucleus Accumbens Rho GTPases in Male and Female C57BL/6 Mice.
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DOI:
10.3389/fnbeh.2022.821080
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发表时间:
2022
影响因子:
3
通讯作者:
Fox ME
Fox ME
中科院分区:
医学3区
文献类型:
--
作者:
Franco D;Wulff AB;Lobo MK;Fox ME

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慢性压力会增加易受伤害个体患药物使用障碍的风险。已经开发了许多模型来探索潜在的神经生物学机制,然而,大多数先前的工作仅限于雄性啮齿动物,仅在大鼠中进行,或者引入可能使阿片类药物研究复杂化的身体损伤。在这里,我们试图确定慢性心理社会压力如何影响雄性和雌性C57 BL/6小鼠的芬太尼消耗。我们使用了慢性社会失败压力(CSDS),或修改的替代慢性证人失败压力(CWDS),并使用社会互动来将小鼠分层为压力敏感或弹性。然后,我们使小鼠在家中笼中接受15天芬太尼饮用范例,该范例包括随着芬太尼浓度的增加而交替的强迫和选择期。对CWDS或CSDS敏感的雄性小鼠相对于未应激的小鼠消耗更多的芬太尼。CWDS敏感的雌性小鼠在强迫期间与无压力的小鼠没有区别,但随着时间的推移,对芬太尼的偏好增加。我们还发现,在应激和芬太尼饮酒后,雄性小鼠的丘脑核Rho GTPases表达减少,但雌性小鼠没有。我们还比较了小鼠的芬太尼饮用行为,这些小鼠可以自由饮用白开水。我们的研究结果表明,压力敏感芬太尼消费依赖于性别和行为结果的压力。
Chronic stress can increase the risk of developing a substance use disorder in vulnerable individuals. Numerous models have been developed to probe the underlying neurobiological mechanisms, however, most prior work has been restricted to male rodents, conducted only in rats, or introduces physical injury that can complicate opioid studies. Here we sought to establish how chronic psychosocial stress influences fentanyl consumption in male and female C57BL/6 mice. We used chronic social defeat stress (CSDS), or the modified vicarious chronic witness defeat stress (CWDS), and used social interaction to stratify mice as stress-susceptible or resilient. We then subjected mice to a 15 days fentanyl drinking paradigm in the home cage that consisted of alternating forced and choice periods with increasing fentanyl concentrations. Male mice susceptible to either CWDS or CSDS consumed more fentanyl relative to unstressed mice. CWDS-susceptible female mice did not differ from unstressed mice during the forced periods, but showed increased preference for fentanyl over time. We also found decreased expression of nucleus accumbens Rho GTPases in male, but not female mice following stress and fentanyl drinking. We also compare fentanyl drinking behavior in mice that had free access to plain water throughout. Our results indicate that stress-sensitized fentanyl consumption is dependent on both sex and behavioral outcomes to stress.
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