Phenotyping a depression-like mouse model by behaviorally induced chronic mild stress

Fabrizio Musacchio1, Sophie Crux1, Felix Nebeling1, Andrea Baral1, Julia Steffen1, Igor Branchi2, Martin Fuhrmann1

1 DZNE Bonn, Germany
2 Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy

Major depressive disorder (MDD) is a common disease of the central nervous system that leads to high socio-economic and clinical challenges. Chronic stress is suggested to be a major risk factor for the disease but little is known about the underlying mechanisms. Here, we use the automated IntelliCage behavioral system that allows standardized and reproducible behavioral experiments, individual animal tracking and analysis. Due to the automatization of the system, human interaction and, therefore, unwanted stress imposed by handling the animals is minimized. In the present approach, we monitor the behavioral parameters, such as the choice between sweetened and unsweetended water or the circadian rhythm. By a standardized IntelliCage protocol, we generate a depression-like phenotype in social groups of adult male mice by behaviorally inducing chronic mild stress. When exposed to different unpredictable stressful stimuli the animals reduce the preference of sweetended water over plain water resulting in an anhedonic phenotype, similar to symptoms of patients suffering MDD. Additionally, we run a behavioral remission protocol for the assessment of the effect of enriched environment on stress.

Our approach is a reliable and reproducible tool for a mouse model of depression. The animals are further investigated by a multimodal approach to better understand the underlying cellular and molecular mechanisms of MDD and, thus, provide new starting points for the development of new therapies for depression.