A mouse model of posttraumatic stress disorder that distinguishes between conditioned and sensitised fear

The pathomechanisms of posttraumatic stress disorder (PTSD) are still unknown, but both fear conditioning and stress sensitisation are supposed to play a crucial role. Hence, valid animal models that model both associative and non-associative components of fear will facilitate elucidation of the biological substrates of the illness, and to develop novel and specific approaches for its prevention and therapy. Here we applied a single electric footshock to C57BL/6N (B6N) and C57BL/6JOla (B6JOla) mice and recorded the conditioned response to contextual trauma reminders (associative fear), the sensitised reaction to a neutral tone in a novel environment (non-associative fear, hyperarousal), social interaction and various emotional behaviours using Modified Holeboard, Test for Novelty-Induced Suppression of Feeding and Forced Swimming Test, after different incubation times (1, 14, 28 days). Freezing generally increased as a function of shock intensity. In B6N mice, sensitised fear was maximal 28 days after trauma and was accompanied by signs of emotional blunting and social withdrawal. B6JOla mice, in contrast, were less susceptible to develop PTSD-like symptoms. The phenotype of B6N exhibited high behavioural variance, allowing distinction between vulnerable and resilient individuals. Only in vulnerable B6N mice, chronic fluoxetine treatment – initiated after an incubation period of 28 days – ameliorated sensitised fear. This new mouse model fulfils common criteria for face and predictive validity and can be used to investigate the biological correlates of individual fear susceptibility, as well as the impact and interrelationship of associative and non-associative fear components in the development and maintenance of PTSD.