Individual baseline behavioral traits predict the resilience phenotype after chronic social defeat

Chronic social defeat (CSD) has been widely used as a psychosocial stress model in mice, with the magnitude of CSD-induced social avoidance as the major behavioral hallmark of the resilient and susceptible groups. Despite significant progress in the study of the neurobiology of resilient and susceptible mice, the nature and ethological relevance of CSD-induced social avoidance and social approach, particularly measured using a CD1 mouse, needs conceptual clarification. Based on the findings of a recent study revealing substantial individuality in genetically homogeneous inbred mice, we investigated whether certain baseline individual characteristics of male C57BL/6J mice predict the resilient outcome after CSD. We focused on two well-studied individual traits that seem to have heritable underpinnings-approach to novelty and avoidance of harm, which are essential for the expression of the exploratory drive. Our results showed that the exploration levels and the approach to novelty and harm were different before and after CSD in resilient and susceptible mice. Before the stress, resilient mice had higher horizontal activity in a novel environment, shorter approach latencies, and higher exploration times for social and non-social targets than susceptible mice. However, susceptible mice performed better in the passive avoidance task than resilient mice as they were more successful in learning to avoid potential adversity by suppressing the spontaneous exploratory drive. Our findings challenge the validity of the current selection criteria for the susceptible and resilient groups and encourage comprehensive assessment of both baseline and stress-induced individual behavioral signatures of mice.