Post-traumatic stress disorder (PTSD) is a psychiatric disorder whose pathogenesis relies on a maladaptive expression of the memory for a life-threatening experience, characterized by over-consolidation, generalization and impaired extinction, which in turn are responsible of dramatic changes in arousal, mood, anxiety and social behavior. Even if human subjects experiencing a traumatic event during lifetime all show an acute response to the trauma, only a subset (susceptible) of them ultimately develops PTSD, meanwhile the others (resilient) fully recover after the first acute response. The majority of the available animal models of PTSD lack of a dynamic dissection to better understand how this acute response can turn into PTSD-related maladaptive changes. Thus, the present project aims at developing an animal model predictive of susceptibility and resilience towards PTSD development. To this aim we will implement our previously validated PTSD animal model in order to differentiate between "low-responders" (LR) and "high-responder" (HR) rats in term of over-consolidation, impaired extinction, enhanced anxiety and social impairment long after trauma exposure.
The majority of animal studies on PTSD does not take into account the susceptibility and the chronicity feature of the human pathology, thus, lacking of translational value. The entire population of animals exposed to a trauma is indeed often considered as "PTSD-like" and only the acute reaction to the trauma is studied. Therefore, the originality of this project relies on the screening and testing of 2 different rat populations: susceptible (HR) and resilient (LR) animals in term of behavioral response to trauma. This will allow us to overcome another main limit of PTSD animal models related to the study of the entire population experiencing a traumatic experiencing without focusing on the fact that only a subset of individuals will develop long lasting behavioral alterations. This project open the way to further studies in which HR and LR rats in such way screened, can be differently manipulated to a better understanding of the neurobiological underpinnings of susceptibility and resilience to PTSD, leading to greater and phenotype-specific therapeutic interventions in humans.