Department of Experimental Medicine. Section of Research and Education. Faculty of Health and Medical Sciences. University of Copenhagen. Blegdamsvej 3, Building 16.1, 2200 Copenhagen N, Denmark.
Department of Experimental Medicine. Section of Research and Education. Faculty of Health and Medical Sciences. University of Copenhagen. Blegdamsvej 3, Building 16.1, 2200 Copenhagen N, Denmark.
J Neurosci Methods. 2023 Jul 15;395:109910. doi: 10.1016/j.jneumeth.2023.109910. Epub 2023 Jun 30.
Exposing rats to repeated unpredictable stressors is a popular method for modelling depression. The sucrose preference test is used to assess the validity of this method, as it measures a rat´s preference for a sweet solution as an indicator of its ability to experience pleasure. Typically, if stressed rats show a lower preference compared to unstressed rats, it is concluded they are experiencing stress-induced anhedonia.
While conducting a systematic review, we identified 18 studies that used thresholds to define anhedonia and to distinguish "susceptible" from "resilient" individuals. Based on their definitions, researchers either excluded "resilient" animals from further analyses or treated them as a separate cohort. We performed a descriptive analysis to understand the rationale behind these criteria.
we found that the methods used for characterizing the stressed rats were largely unsupported. Many authors failed to justify their choices or relied exclusively on referencing previous studies. When tracing back the method to its origins, we converged on a pioneering article that, although employed as a universal evidence-based justification, cannot be regarded as such. What is more, through a simulation study, we provided evidence that removing or splitting data, based on an arbitrary threshold, introduces statistical bias by overestimating the effect of stress.
Caution must be exercised when implementing a predefined cut-off for anhedonia. Researchers should be aware of potential biases introduced by their data treatment strategies and strive for transparent reporting of methodological decisions.
反复暴露于不可预测的应激源是一种模拟抑郁的常用方法。蔗糖偏好测试用于评估这种方法的有效性，因为它可以测量大鼠对甜味溶液的偏好，作为其体验愉悦能力的指标。通常，如果应激大鼠与未应激大鼠相比表现出较低的偏好，就可以得出它们正在经历应激诱导的快感缺失的结论。
在进行系统评价时，我们确定了 18 项使用阈值来定义快感缺失并区分“易感”和“弹性”个体的研究。根据他们的定义，研究人员要么将“弹性”动物排除在进一步分析之外，要么将它们视为一个单独的队列。我们进行了描述性分析，以了解这些标准背后的原理。
我们发现，用于描述应激大鼠的方法在很大程度上没有得到支持。许多作者未能证明他们的选择是合理的，或者只是依赖于引用以前的研究。当追溯到方法的起源时，我们发现了一篇开创性的文章，尽管它被用作普遍的循证依据，但不能被视为这样的依据。更重要的是，通过一项模拟研究，我们提供了证据表明，基于任意阈值去除或拆分数据会通过高估应激的影响而引入统计偏差。
在实施快感缺失的预设截止值时必须谨慎。研究人员应该意识到其数据处理策略引入的潜在偏差，并努力透明地报告方法决策。
