Can I Get a Witness? Using Vicarious Defeat Stress to Study Mood-Related Illnesses in Traditionally Understudied Populations

Abstract

The chronic social defeat stress model has been instrumental in shaping our understanding of neurobiology relevant to affect-related illnesses, including major depressive disorder. However, the classic chronic social defeat stress procedure is limited by its exclusive application to adult male rodents. We have recently developed a novel vicarious social defeat stress procedure wherein one mouse witnesses the physical defeat bout of a conspecific from the safety of an adjacent compartment. This witness mouse develops a similar behavioral phenotype to that of the mouse that physically experiences social defeat stress, modeling multiple aspects of major depressive disorder. Importantly, this new procedure allows researchers to perform vicarious social defeat stress in males or females and in juvenile mice, which typically are excluded from classic social defeat experiments. Here we discuss several recent advances made using this procedure and how its application provides a new preclinical approach to study the neurobiology of psychological stress-induced phenotypes.

Keywords: Adolescent; Animal model; Anxiety; Depression; Female; Psychological stress; Social defeat; Witness defeat.

Figure 1:. Vicarious Social Defeat Stress Procedure.

The adult male C57BL/6 physical target intruder mouse (P) is placed into the divided cage with a resident adult male retired breeder CD1 aggressor mouse (A1), while the witness intruder mouse (W) is placed across the divider. Critically, the witness mouse can be either sex and adolescent or adult. After a 10-minute stress interaction involving physical aggression of the resident (A1) against the physical target (P), the witness mouse (W) is moved to a new cage, where it is housed across a divider from a different resident male retired breeder CD1 aggressor mouse (A2), while the physical target intruder mouse (P) is placed across the divider from the original aggressor mouse (A1), and the mice are co-housed for 24-hours. This process then repeats for a total of 10 consecutive days.