The impact of prior exposure to severe stressors on fear learning: The critical contribution of the type of stressor and the rat strain

The appearance of long-lasting behavioral alterations is considered critical for the characterization of acute stressors as putative animal models of PTSD. However, the traumatic nature of the different stressors used is objectively difficult to demonstrate and literature is plagued by inconsistent results. In the present study we wanted to demonstrate the relevance of qualitative aspects of stressors not linked to their severity (as evaluated by classical biological markers) and how the use of different mouse or rat strains can contribute to the inconsistencies. We then exposed Sprague-Dawley (SD) and Long-Evans (LE) rats to two different severe stressors of roughly similar intensity, immobilization on boards (IMO) and inescapable foot-shocks (IS), and studied their impact on contextual fear conditioning, generalization, extinction and extinction recall. The results confirmed that the two stressors are of similar severity (IMO a little bit more severe) in terms of biological markers of stress, but their impact of fear conditioning was strongly dependent on the stressor and the strain, with a strong impact of IS in LE rats, a modest impact of IMO in the latter strain and almost null impact of the two stressors in SD rats. We thus confirm the relevance of both qualitative aspects of stressors and the strain used in order to characterize appropriate models of PTSD. Deciphering the processes underlying the contribution of the two factors is fundamental and requires comparison of stressors and strains at different neurobiological levels.