In the behavioral profiling of vulnerability and resilience in animal models of Post-Traumatic Stress Disorder (PTSD), the focus has been on the effects that the stress protocol generates in the exposed animals. Although this post-stress classification is more sensitive than a traditional comparison, it is insufficient to account for intra-subject variation. This is possible if a pre-stress measurement is available, which allows a more accurate characterization of the effects of the stress protocol and an investigation of susceptibility.
To evaluate this, we conducted experiments with adult male C57BL6 mice in which the Single Prolonged Stress (SPS) protocol was preceded by an assessment of anxiety-like behavior with the open field test (OFT). One week after the SPS, we conducted a test in the Elevated Plus Maze and a second OFT. After this, contextual fear conditioning was performed on a subset of animals to assess its retrieval, generalization and extinction. The pre-stress measurement prevents us from attributing post-stress “effects” to the independent variable when these were better explained by their basal anxiety-like behavior. At the same time, it shows that a considerable proportion of the most affected SPS-mice were susceptible, suggesting that it is a risk factor that should be considered as an outcome by itself and a relevant variable to be controlled in PTSD models.