Kim, J.; Kim, C. S.

Background Chronic social defeat stress (CSDS) leads to persistent behavioral deficits, such as social avoidance and abnormal stress responses, including freezing. Despite these fear-based responses observed during and after social defeat, the effects of prolonged exposure (PE) treatment, a well-established therapy for post-traumatic stress disorder (PTSD), have not been thoroughly investigated in this context. Methods Socially defeated male mice were subjected to 12 days of PE treatment. We determined the efficacy of PE treatment in physically defeated mice by measuring stress responses, including freezing, jump escape, and social interaction, before and after the intervention. Results After 12 days of PE treatment, male mice that had been physically defeated showed a marked decrease in freezing behavior. Furthermore, PE treatment changed the phenotype of mice from susceptible to resilient by reducing social avoidance during the social interaction test. Conclusions These results provide a new preclinical method for investigating behavioral recovery and adaptation by showing that PE treatment can reverse significant behavioral deficits caused by social defeat stress. A new framework for examining individual variability in therapeutic outcomes after chronic stress exposure is provided by the emergence of both treatment-responsive and treatment-resistant phenotypes.