FROM EARLY LIFE STRESS TO ADULT OUTCOMES: A JUVENILE SOCIAL DEFEAT MODEL IN MICE

Early life adversity, including child maltreatment, has devastating and long lasting consequences on brain development, leading to social, emotional and cognitive deficits^​. It is one of the strongest predictors of psychiatric pathologies such as depression and suicide^​. However, some individuals resist it, demonstrating adaptive capacity known as resilience^​. Understanding the mechanisms behavioural and biological underlying resilience, enabling emotional and cognitive balance to be maintained into adulthood, is essential to identify new therapeutic targets. The objective of this study was to develop a mice model of early life adversity using a social defeat stress paradigm applied to juvenile C57BL/6J males and females at postnatal days 21. Although similar models have been extensively used in adults and adolescents^​, their application earlier developmental stages remains insufficiently explored. In the proposed protocol, juvenile mice were exposed to an aggressive CD1 mouse 3 to 5 minutes per day over a minimum of 6 consecutive days. Body weight gain was measured weekly andserum corticosterone levels at baseline and after one or six of defeat to assess physiological stress response. Social interaction was evaluated 24 hours after the last defeat session to segregate animals into susceptible and resilient phenotypes. In adulthood, a second interaction test was conducted to identify how these phenotypes evolve during development. Anxiety and depression-like behaviors were further assessed using a battery of validated behavioural assays, including the elevated plus maze, forced swim test, marble burying test, novelty suppressed feeding test, and sucrose preference test.