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Automated quantification of opioid withdrawal in neonatal rat pups using Ethovision® XT software
Neurotoxicology and Teratology ( IF 2.6 ) Pub Date : 2021-01-30 , DOI: 10.1016/j.ntt.2021.106959
Hanna J Kulbeth 1 , Saki Fukuda 2 , Lisa K Brents 2
Affiliation  

Chronic prenatal exposure to opioids often causes fetal opioid dependence that leads to neonatal opioid withdrawal syndrome (NOWS) shortly after delivery. Rat models of NOWS often require quantifying neonatal withdrawal behaviors using time-consuming, labor-intensive manual scoring methods. The goal of this study was to automate quantification of opioid withdrawal in neonatal rat pups. Accordingly, we used the animal behavior software Ethovision® XT to analyze archived videos of rat pups subjected to precipitated opioid withdrawal testing on postnatal day 0. We compared results obtained from Ethovision® XT with those previously obtained from manual scoring. Two endpoints reported by Ethovision® XT, Distance Moved (cm) and Movement Duration (s), had strong positive linear relationships with manually derived global withdrawal scores (GWS; R2 > 0.73). Sensitivity and specificity of each endpoint to discriminate presence and absence of low-grade withdrawal were assessed by receiver operator characteristic curve analysis, which indicated that Distance Moved and Movement Duration had excellent accuracy (AUC > 0.90). Finally, we analyzed main and interaction effects of prenatal treatment (with vehicle or mu opioid receptor full agonists) and postnatal challenge (with saline or an opioid receptor antagonist) on each endpoint and determined they were similar for the manual and automated methods. These results show that Ethovision® XT software can reliably quantify opioid withdrawal in neonatal rat pups with non-inferiority to manual scoring even in videos that were not originally purposed and optimized for Ethovision® XT analysis. This faster and less labor-intensive method of analysis is expected to accelerate progress in preclinical studies of NOWS.



中文翻译:

使用 Ethovision® XT 软件自动量化新生幼鼠的阿片类药物戒断

产前长期接触阿片类药物通常会导致胎儿阿片类药物依赖,从而导致新生儿在分娩后不久出现阿片类药物戒断综合征 (NOWS)。NOWS 的大鼠模型通常需要使用耗时、劳动密集型的手动评分方法来量化新生儿戒断行为。本研究的目的是对新生大鼠幼鼠的阿片类药物戒断进行自动量化。因此,我们使用动物行为软件 Ethovision® XT 来分析在出生后第 0 天接受阿片类药物戒断试验的大鼠幼崽的存档视频。我们将 Ethovision® XT 获得的结果与之前通过手动评分获得的结果进行了比较。Ethovision® XT 报告的两个端点,即移动距离 (cm) 和运动持续时间 (s),与手动得出的全局退出分数 (GWS; R) 具有很强的正线性关系2个 > 0.73)。通过接受者操作员特征曲线分析评估每个端点区分存在和不存在低度戒断的敏感性和特异性,这表明移动距离和运动持续时间具有出色的准确性(AUC > 0.90)。最后,我们分析了产前治疗(使用载体或 μ 阿片受体完全激动剂)和产后治疗(使用生理盐水或阿片受体拮抗剂)对每个终点的主要影响和相互作用,并确定它们对于手动和自动方法是相似的。这些结果表明,Ethovision® XT 软件可以可靠地量化新生幼鼠的阿片类药物戒断情况,即使在最初并非针对 Ethovision® XT 分析而优化的视频中也不逊色于手动评分。

更新日期:2021-02-03
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