Abstract
Stress-related illnesses such as major depressive and anxiety disorders are characterized by maladaptive physiological or behavioral responses to stressful life event. Chronic stress-based animal models have provided critical insight to a better understanding of these responses. However, currently available behavioral assays measuring chronic stress-induced phenotype in mice are limited in their design (short, not repeatable, subject to experimenter-bias) and are often inconsistent. Using the Noldus PhenoTyper apparatus, we developed a new tool to repeatedly assess behavioral changes induced by chronic stress exposure in two mouse models i.e. chronic restraint stress (CRS) and chronic unpredictable mild stress (UCMS). The PhenoTyper test consists on monitoring in home-cage setting the overnight animals’ behavior before, during and after a 1hr light challenge is applied over the food zone. After, characterization of the test, we compared the reproducibility and reliability of the PhenoTyper test in assessing the effects of chronic stress exposure, with commonly-used tests such as the elevated plus maze, open-field, novelty suppressed feeding and novelty-induced hypophagia. We found that while stress mice display heterogeneous profiles in these tests, CRS- and UCMS-exposed mice showed a very consistent response in the PhenoTyper test. Indeed, CRS and UCMS mice continue avoiding the lit zone in favor of the shelter zone. This behavior, or residual avoidance after the light challenge, lasted for hours beyond termination of the challenge, was not observed after acute stress and was consistently found throughout the chronic stress exposure in both models. Chronic stress-induced residual avoidance in the shelter was alleviated by chronic imipramine treatment but not acute diazepam administration. This new tool should be instrumental in design of longitudinal studies aiming to better understanding the trajectory of chronic stress-induced deficits in animal models and potentially screen novel anxiolytic and antidepressant treatments.