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I. MORGANSTERN, S. DAVIS, K. HOMA, E. SABATH, T. HANANIA

The Chronic Social Defeat Stress (CSDS) mouse model has received much interest recently as it closely mimics the dynamic range of individual responses to stressors such as the development of a major depressive disorder, anxiety, post-traumatic stress disorder or resil¬iency to these disease states. Such individual responses to social stressors are particularly useful in modeling aspects of depression- and anxiety-like behavior with high construct, face, discriminative and predictive validity. The CSDS mouse model employed here for testing was based on previous published work by Golden et al., 2011, as well as several others. Our goal in using this multifaceted model was two-fold 1) to confirm and further characterize the distinct behavioral traits in animals most susceptible to social stress after going through the 10-day social defeat paradigm compared to undefeated control animals; 2) to provide pharmacological validation for this model using standard antidepressant medications such as fluoxetine and imipramine.

Our findings first confirmed previous work with this model in demonstrating that compared to undefeated control animals, mice most susceptible to social defeat stress demonstrated a number of abnormalities in social avoidance, depression and anxiety as measured by routine test procedures. Most interesting are the findings with our proprietary algorithm-based behavioral SmartCube ® system, which measures whole animal behavior. These analyses demonstrated very unique and specific features of the susceptible versus control mice, which include a hypoactive and anxious phenotype with reduced mobility, rearing, digging and sniffing as well as increased freezing and exploratory stretching behavior. This phenotype of susceptible mice showed very high discrimination from control undefeated animals, which was evident as long as 6 weeks after the social defeat stress. Our data also demonstrated that chronic treatment with standard antidepressant medications, fluoxetine and imipramine was able to attenuate the distinct phenotype of stress-susceptible mice.

In summary, by using this platform of routine depression and anxiety tests in conjunction with more sophisticated computer vision systems such as SmartCube ®, we hope to optimize drug screening using this CSDS model, which captures several important aspects of affect including depression, anxiety and also post-traumatic stress.