Vulnerability and resilience toward post-traumatic stress disorder (PTSD): behavioral and transcriptomic characterization of two unique PTSD rat lines

Background: After experiencing a traumatic event, stress coping mechanisms may become dysfunctional leading to the development of psychiatric disorders, such as post-traumatic stress disorder (PTSD). Interestingly, only a subset of subjects develops PTSD (susceptible), whilst most of the trauma victims fully recovers after the first acute physiological response (resilient). However, the etiopathogenesis of PTSD and the neurobiological mechanisms underlying the emergence of susceptible and resilient PTSD phenotypes remain largely unknown. Therefore, the aim of this study was to identify molecular mechanisms underlying PTSD vulnerability and resilience. Methods: By selective breeding of Sprague-Dawley rats, screened based on post-trauma behavioral indicators of PTSD-like vulnerability (or resilience) (Colucci et al. 2020 Transl Psychiatry 10:243), we generated two distinct lines of PTSD-like susceptible (SUS) and resilient (RES) rats. Results: Data collected so far, on the 11th generations (F11), indicated a marked distinction between the two phenotypes in terms of behavioral indices of traumatic memory (i.e., increased traumatic memory consolidation and recall, and reduced extinction in SUS vs RES) and post-trauma sociability (i.e., reduced sociability in SUS vs RES) in males and females. Furthermore, transcriptome analysis (RNA sequencing) within the amygdala showed differentially expressed genes between naïve SUS and RES rats of both sexes never exposed to a traumatic experience. Conclusion: The availability of such SUS and RES lines of rats represents an unprecedented tool to determine mechanisms of PTSD vulnerability or resilience and identify new targets for prophylactic and/or therapeutic interventions for the treatment of trauma-related disorders.