Computational Analysis of Multidimensional Behavioral Alterations After Chronic Social Defeat Stress

Abstract

BackgroundThe study of depression in humans depends on animal models that attempt to mimic specific features of the human syndrome. Most studies focus on one or a few behavioral domains, with time and practical considerations prohibiting a comprehensive evaluation. Although machine learning has enabled unbiased analysis of behavior in animals, this has not yet been applied to animal models of psychiatric disease. MethodsWe performed chronic social defeat stress (CSDS) in mice and evaluated behavior with PsychoGenics’ SmartCube, a high-throughput unbiased automated phenotyping platform that collects >2000 behavioral features based on machine learning. We evaluated group differences at several times post-CSDS and after administration of the antidepressant medication imipramine. ResultsSmartCube analysis after CSDS successfully separated control and defeated-susceptible mice, and defeated-resilient mice more resembled control mice. We observed a potentiation of CSDS effects over time. Treatment of susceptible mice with imipramine induced a 40.2% recovery of the defeated-susceptible phenotype as assessed by SmartCube. ConclusionsHigh-throughput analysis can simultaneously evaluate multiple behavioral alterations in an animal model for the study of depression, which provides a more unbiased and holistic approach to evaluating group differences after CSDS and perhaps can be applied to other mouse models of psychiatric disease.