Modeling spontaneous opioid withdrawal in male and female outbred mice using traditional endpoints and hyperalgesia
Modeling spontaneous opioid withdrawal in male and female outbred mice using traditional endpoints and hyperalgesia
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DOI：
10.1097/fbp.0000000000000714
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发表时间：
2023-04-01
影响因子：
1.6
通讯作者：
Quock, Raymond M.
中科院分区：
文献类型：
--
作者：
Brewer, Abigail L.;Lewis, Christina C.;Quock, Raymond M.
阿片类药物的戒断严重影响药物依赖周期，因为与戒断相关的痛觉过敏往往是继续使用药物的一个原因。成瘾动物模型是研究药物依赖和戒断如何不仅影响正常神经回路，也影响潜在治疗依赖和戒断的有效性的重要工具。我们对雄性和雌性杂交小鼠的自发吗啡戒断的时间进程进行了研究，该研究可以用传统的躯体终点和机械痛觉过敏作为戒断的终点来检验雄性和雌性小鼠的性别差异。瑞士国立卫生研究院(NIH)的雄性和雌性小鼠采用递增给药方案使其对吗啡产生依赖。5天后停止注射。在最后一次注射后106h的时间间隔内评估戒断行为。对前爪颤抖、湿狗抖动、跳跃和其他行为的次数进行了评分，得出了全球得分。爪压读数随后也被用来跟踪随着时间的推移对痛苦刺激的敏感性的变化。雄性和雌性小鼠的戒断严重程度大致相似，根据综合全球评分，在最后一次注射后24小时达到峰值。女性确实比男性表现出更早、更频繁的震颤。虽然男性和女性在戒断过程中表现出类似的痛觉过敏，但女性恢复得更快。在雄性和雌性NIH瑞士小鼠中，自发的阿片类药物戒断在24小时达到高峰。我们还成功地证明了痛觉过敏是一个随戒断过程而变化的终点。
Opioid withdrawal significantly impacts drug dependence cycles as hyperalgesia associated with withdrawal is often a reason for continued drug use. Animal models of addiction are important tools for studying how drug dependence and withdrawal impact not only normal neurocircuitry but also the effectiveness of potential treatments for dependence and withdrawal. We conducted a study of the time course of spontaneous morphine withdrawal in outbred male and female mice that can be used to examine sex differences in male and female mice using both traditional somatic endpoints and mechanical hyperalgesia as an endpoint of withdrawal. Male and female national institute of health (NIH) Swiss mice were made dependent upon morphine using an escalating dosing schedule. Injections were stopped after 5days. Withdrawal behavior was assessed at time intervals up to 106h after the final injection. Numbers of forepaw tremors, wet-dog shakes, jumps and other behaviors were scored to create a global score. Paw pressure readings were then also taken to track changes in sensitivity to a painful stimulus over time. Male and female mice had approximately similar withdrawal severity peaking at 24h after the final injection as measured by composite global scores. Females did exhibit an earlier and greater frequency of tremors than males. Although males and females showed similar hyperalgesia during withdrawal, females recovered faster. Spontaneous opioid withdrawal peaking at 24h was demonstrated in male and female NIH Swiss mice. We also successfully demonstrated that hyperalgesia is an endpoint that varies over the course of withdrawal.