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    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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    Author
    Franco, Daniela
    Wulff, Andreas B
    Lobo, Mary Kay
    Fox, Megan E
    Date
    2022-02-10
    Journal
    Frontiers in Behavioral Neuroscience
    Publisher
    Frontiers Media S.A.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3389/fnbeh.2022.821080
    Abstract
    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.
    Rights/Terms
    Copyright © 2022 Franco, Wulff, Lobo and Fox.
    Keyword
    chronic stress
    fentanyl
    nucleus accumbens
    sex differences
    synthetic opioids
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/18131
    ae974a485f413a2113503eed53cd6c53
    10.3389/fnbeh.2022.821080
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