Modeling spontaneous opioid withdrawal in male and female outbred mice using traditional endpoints and hyperalgesia.

IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES
Abigail L Brewer, Christina C Lewis, Liudmyla Eggerman, Alexis Blokker, John A Burkland, Megan Johnsen, Raymond M Quock
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引用次数: 3

Abstract

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 5 days. Withdrawal behavior was assessed at time intervals up to 106 h 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 24 h 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 24 h 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.

使用传统终点和痛觉过敏方法对雄性和雌性远交种小鼠的自发性阿片类药物戒断进行建模。
阿片类药物戒断会显著影响药物依赖周期,因为与戒断相关的痛觉过敏往往是继续使用药物的原因。成瘾动物模型是研究药物依赖和戒断如何影响正常神经回路以及潜在治疗药物依赖和戒断的有效性的重要工具。我们在近亲繁殖的雄性和雌性小鼠中进行了一项自发吗啡戒断的时间过程研究,该研究可以用来检查雄性和雌性小鼠的性别差异,使用传统的躯体终点和机械痛觉过敏作为戒断终点。瑞士国立卫生研究院(NIH)的雄性和雌性小鼠使用逐步增加的剂量计划依赖吗啡。5天后停止注射。在最后一次注射后106小时的时间间隔内评估戒断行为。前爪震颤、湿狗抖动、跳跃和其他行为的数量被评分,以创建一个全局得分。随后,研究人员还通过脚掌压力读数来追踪疼痛刺激敏感性随时间的变化。根据综合整体评分,雄性和雌性小鼠在最后一次注射后24小时的戒断严重程度达到顶峰。女性确实比男性表现出更早、更频繁的震颤。虽然雄性和雌性在停药期间表现出相似的痛觉过敏,但雌性恢复得更快。在雄性和雌性NIH瑞士小鼠中,24小时出现自发性阿片类药物戒断高峰。我们也成功地证明痛觉过敏是一个终点,在撤药过程中变化。
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来源期刊
Behavioural Pharmacology
Behavioural Pharmacology 医学-行为科学
CiteScore
3.40
自引率
0.00%
发文量
84
审稿时长
6-12 weeks
期刊介绍: Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.
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