From Trauma to PTSD: Dissecting Vulnerability and Resilience in a Rat Model

Background. After a traumatic event, dysfunctional stress coping can lead to psychiatric disorders such as post-traumatic stress disorder (PTSD). However, only a subset of trauma-exposed individual develops PTSD, and the factors driving vulnerability or resilience remain largely unknown. Methods. We have previously developed a rat model that allows early post-trauma behavioral differentiation between susceptible (SUS) and resilient (RES) PTSD-like phenotypes in both sexes [1,2], and through selective breeding, we have established two distinct SUS and RES PTSD-like rat lines. Here, we assessed the behavioral profiles of these SUS and RES rats, and performed bulk RNA sequencing in PTSD-related brain regions under basal condition to identify markers of susceptibility and resilience. Results. Our results showed a clear phenotypic distinction, with SUS rats exhibiting fear memory deficits (i.e., enhanced traumatic memory consolidation, recall, and impaired extinction) and socio-emotional alterations compared to RES rats. Transcriptomic profiling revealed marked baseline differences between the two phenotypes, with a greater number of differentially expressed genes in females. Gene ontology enrichment analysis highlighted sex- and brain region- specific alterations in pathways related to stress and memory. Conclusions. These findings provide novel insights into the molecular basis of PTSD vulnerability/resilience and support the use of these SUS/RES rat lines as a translational model for identifying preventive or therapeutic targets for trauma-related disorders. References: [1] Colucci et al., 2020. Transl Psychiatry. 10(1):243 [2] Chiacchierini et al., 2025. J Neurosci Methods. 416:110380