Multidimensional behavioral profiles associated with resilience and susceptibility after inescapable stress

Abstract

ABSTRACTStress-related neuropsychiatric disorders are complex conditions that are difficult to diagnose and treat due to the variety of symptoms they present with. While animal models have been instrumental in understanding their underlying mechanisms, there is an ongoing debate about the validity of behavioral measures to address specific disorders. Here, we conducted an extensive ethological characterization of behavioral variables associated with anxiety and depression and employed a multidimensional approach to investigate stress susceptibility in male Wistar rats. The rats underwent inescapable footshocks (IS) or no-shocks (NS), followed by a comprehensive battery of behavioral tests over several days. Our study identified phenotypically distinct clusters, including fully characterized stress-susceptible and stress-resilient subpopulations, along with intermediate phenotypes. Reduced time in elevated plus maze open arms, diminished sucrose preference and increased escape failures consistently differentiated susceptible from resilient rats. Behavior in the forced swim test was unrelated to stress susceptibility. In conclusion, our study sheds light on the relationships between classical behavioral measures in animal models of depression, highlighting distinct patterns that differentiate susceptibility from resilience. It emphasizes the importance of a multidimensional assessment of behavioral responses in animal models for a better understanding of stress-related neuropsychiatric disorders.HIGHLIGHTSClustering of features reveals a correlation pattern that separates behavioral variables associated with susceptibility from those associated with resilience to stressMultidimensional patterns of covariation among behavioral measures distinguish helpless from non-helpless individuals and indicate independence from forced swim test behavior.Clustering of individuals discriminates stressed subjects and reveals multidimensional behavioral phenotypes of resilience and susceptibility, indicating different stress-coping strategies.