Animal models in psychiatric research are indispensable for insights into mechanisms of behaviour and mental disorders. Distress is an important aetiological factor in psychiatric diseases, especially depression, and is often used to mimic the human condition. Modern bioethics requires balancing scientific progress with animal welfare concerns. Therefore, scientifically based severity assessment of procedures is a prerequisite for choosing the least compromising paradigm according to the 3Rs principle. Evidence-based severity assessment in psychiatric animal models is scarce, particularly in depression research. Here, we assessed severity in a cognitive depression model by analysing indicators of stress and well-being, including physiological (body weight and corticosterone metabolite concentrations) and behavioural (nesting and burrowing behaviour) parameters. Additionally, a novel approach for objective individualised severity grading was employed using clustering of voluntary wheel running (VWR) behaviour. Exposure to the paradigm evoked a transient elevation of corticosterone, but neither affected body weight, nesting or burrowing behaviour. However, the performance in VWR was impaired after recurrent stress exposure, and the individual severity level increased, indicating that this method is more sensitive in detecting compromised welfare. Interestingly, the direct comparison to a somatic, chemically induced colitis model indicates less distress in the depression model. Further objective severity assessment studies are needed to classify the severity of psychiatric animal models in order to balance validity and welfare, reduce the stress load and thus promote refinement.

中文翻译：

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在广泛使用的小鼠认知抑郁模型中对严重性进行系统分析。

精神病学研究中的动物模型对于洞察行为和精神障碍的机制是必不可少的。困扰是精神疾病尤其是抑郁症的重要病因，通常被用来模仿人类的状况。现代生物伦理学要求在科学进步与动物福利问题之间取得平衡。因此，基于科学的程序严重性评估是根据3Rs原则选择影响最小的范例的前提。精神病动物模型中缺乏基于证据的严重性评估，尤其是在抑郁症研究中。在这里，我们通过分析压力和幸福感的指标来评估认知抑郁模型中的严重程度，包括生理参数（体重和皮质酮代谢物浓度）和行为参数（嵌套和穴居行为）。此外，采用了一种自愿车轮行驶（VWR）行为聚类的客观个性化严重程度分级的新方法。暴露于该范式会引起皮质酮的短暂升高，但不会影响体重，筑巢或穴居行为。但是，反复暴露于压力下后，VWR的性能受损，个体严重程度升高，表明该方法在检测受损的福利方面更为敏感。有趣的是，与体细胞化学诱导的结肠炎模型的直接比较表明，抑郁模型的困扰较小。