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    Divergent profiles of fentanyl withdrawal and associated pain in mice and rats

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    Author
    Uddin, Olivia
    Jenne, Carleigh cc
    Fox, Megan E
    Arakawa, Keiko
    Keller, Asaf
    Cramer, Nathan
    Date
    2020-12-11
    Journal
    Pharmacology, Biochemistry, and Behavior
    Publisher
    Elsevier Ltd.
    Type
    Article
    
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    https://doi.org/10.1016/j.pbb.2020.173077
    Abstract
    Opioid abuse has devastating effects on patients, their families, and society. Withdrawal symptoms are severely unpleasant, prolonged, and frequently hinder recovery or lead to relapse. The sharp increase in abuse and overdoses arising from the illicit use of potent and rapidly-acting synthetic opioids, such as fentanyl, highlights the urgency of understanding the withdrawal mechanisms related to these drugs. Progress is impeded by inconsistent reports on opioid withdrawal in different preclinical models. Here, using rats and mice of both sexes, we quantified withdrawal behaviors during spontaneous and naloxone-precipitated withdrawal, following two weeks of intermittent fentanyl exposure. We found that both mice and rats lost weight during exposure and showed increased signs of distress during spontaneous and naloxone precipitated withdrawal. However, these species differed in their expression of withdrawal associated pain, a key contributor to relapse in humans. Spontaneous or ongoing pain was preferentially expressed in rats in both withdrawal conditions, while no change was observed in mice. In contrast, withdrawal associated thermal hyperalgesia was found only in mice. These data suggest that rats and mice diverge in how they experience withdrawal and which aspects of the human condition they most accurately model. These differences highlight each species' strengths as model systems and can inform experimental design in studies of opioid withdrawal.
    Rights/Terms
    Copyright © 2020 Elsevier Inc. All rights reserved.
    Keyword
    Fentanyl
    Mice
    Pain
    Rats
    Substance Withdrawal Syndrome
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/14303
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.pbb.2020.173077
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