de Oliveira-Júnior Benedito Alves, Marques Danilo Benette, Rossignoli Matheus Teixeira, Prizon Tamiris, Leite João Pereira, Ruggiero Rafael Naime
Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Sci Rep. 2024 Apr 27;14(1):9699. doi: 10.1038/s41598-024-59984-7.
Clinical depression is characterized by multiple concurrent symptoms, manifesting as a complex heterogeneous condition. Although some well-established classical behavioral assessments are widespread in rodent models, it remains uncertain whether rats also display stress-induced depression-related phenotypes in a multidimensional manner, i.e., simultaneous alterations in multiple behavioral tests. Here, we investigated multivariate patterns and profiles of depression-related behavioral traits in male Wistar rats subjected to inescapable footshocks (IS) or no-shocks (NS), followed by a comprehensive battery of behavioral tests and ethological characterization. We observed generalized stronger intra-test but weaker inter-test correlations. However, feature clustering of behavioral measures successfully delineated variables linked to resilience and susceptibility to stress. Accordingly, a noteworthy covariation pattern emerged, characterized by increased open field locomotion, reduced time in the elevated plus maze open arms, lower sucrose preference, and increased shuttle box escape failures that consistently differentiated IS from NS. Surprisingly there is little contribution from forced swim. In addition, individual clustering revealed a diversity of behavioral profiles, naturally separating NS and IS, including subpopulations entirely characterized by resilience or susceptibility. In conclusion, our study elucidates intricate relationships among classical depression-related behavioral measures, highlighting multidimensional individual variability. Our work emphasizes the importance of a multivariate framework for behavioral assessment in animal models to understand stress-related neuropsychiatric disorders.
临床抑郁症的特征是多种并发症状，表现为一种复杂的异质性疾病。尽管一些成熟的经典行为评估方法在啮齿动物模型中广泛应用，但大鼠是否也以多维方式表现出应激诱导的抑郁相关表型，即在多个行为测试中同时发生改变，仍不确定。在此，我们研究了遭受不可逃避电击（IS）或未电击（NS）的雄性Wistar大鼠抑郁相关行为特征的多变量模式和概况，随后进行了一系列全面的行为测试和行为学特征分析。我们观察到测试内相关性普遍更强，但测试间相关性较弱。然而，行为测量的特征聚类成功地描绘了与恢复力和应激易感性相关的变量。因此，出现了一种值得注意的协变模式，其特征是旷场运动增加、高架十字迷宫开放臂停留时间减少、蔗糖偏好降低以及穿梭箱逃避失败增加，这些一致地区分了IS组和NS组。令人惊讶的是，强迫游泳的贡献很小。此外，个体聚类揭示了多种行为概况，自然地将NS组和IS组分开，包括完全以恢复力或易感性为特征的亚群。总之，我们的研究阐明了经典抑郁相关行为测量之间的复杂关系，突出了多维个体变异性。我们的工作强调了多变量框架在动物模型行为评估中的重要性，以理解与应激相关的神经精神疾病。
