Abstract
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 are responsible of dramatic changes in arousal, mood, anxiety, and social behavior. Even if subjects experiencing a traumatic event during lifetime all show an acute response to the trauma, only a subset of them (susceptible) ultimately develops PTSD, meanwhile the others (resilient) fully recover after the first acute response. However, the dynamic relationships between the interacting brain circuits that might potentially link trauma-related experiences to the emergence of susceptible and resilient PTSD phenotypes in individuals is not well understood. Toward the first step to reach this goal, we have implemented our experimental PTSD model previously developed, making it suitable to differentiate between susceptible (high responders, HR) and resilient (low responders, LR) rats in terms of over-consolidation, impaired extinction, and social impairment long after trauma. Rats were exposed to five footshocks paired with social isolation. One week after trauma but before extinction, animals were tested in the Open Field and Social Interaction tasks for the identification of a predictive variable to identify susceptible and resilient animals before the possible appearance of a PTSD-like phenotype. Our findings show that exploratory activity after trauma in a novel environment is a very robust variable to predict susceptibility towards a PTSD-like phenotype. This experimental model is thus able to screen and differentiate, before extinction learning and potential therapeutic intervention, susceptible and resilient PTSD-like rats.
Highlights
Post-traumatic stress disorder (PTSD) is a pathology with high prevalence and morbidity, the abnormal adaptation to a traumatic experience represents its specific pathogenic starting point[1,2,3]
To this aim we performed a correlation analysis between potentially predictive variables and other behavioral outcomes associated with PTSD
We found a significant negative correlation between the total distance traveled, which is an index of the exploratory activity, in the Open Field test performed 5 days after trauma exposure and the freezing behavior shown by rats during the first extinction session (R = −0.491, P < 0.0001) (Fig. 2a), index of the over-consolidation of the trauma experience in the PTSD model, and the freezing behavior shown by rats during the extinction retention test (R = −0.532, P < 0.0001) (Fig. 2b), index of the impaired extinction of the trauma experience in the PTSD model
Summary
Post-traumatic stress disorder (PTSD) is a pathology with high prevalence and morbidity, the abnormal adaptation to a traumatic experience represents its specific pathogenic starting point[1,2,3]. The formation, consolidation, retrieval, and extinction of fear memories associated to a traumatic situation are orchestrated by multiple brain regions that act in a coordinate manner to elaborate the acute response to trauma[4,5,6]. After this normal acute response, most subjects fully recover. After development and consecutive symptoms (e.g., dramatic changes in arousal, mood, and social behavior)[1,3]. An important question arises on why some people do develop
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