Psychosocial predator-based animal model of PTSD produces physiological and behavioral sequelae and a traumatic memory four months following stress onset

- PTSD-like sequelae induced by psychosocial stress persisted for at least 4 months.
- Predator exposure generated a persistent fear-conditioned “traumatic” memory.
- Psychosocial stress resulted in a long-term increase in anxiety and impaired cognition.
- Predator-based psychosocial stress resulted in persistent physiological changes comparable to PTSD-like symptoms.

We have a well-established animal model of PTSD composed of predator exposure administered in conjunction with social instability that produces PTSD-like behavioral and physiological abnormalities one month after stress initiation. Here, we assessed whether the PTSD-like effects would persist for at least 4 months after the initiation of the psychosocial stress regimen. Adult male Sprague-Dawley rats were exposed to either 2 or 3 predator-based fear conditioning sessions. During each session, rats were placed in a chamber for a 3-min period that terminated with a 30-s tone, followed by 1 h of immobilization of the rats during cat exposure (Day 1). All rats in the stress groups received a second fear conditioning session 10 days later (Day 11). Half of the stress rats received a third fear conditioning session 3 weeks later (Day 32). The two cat-exposed groups were also exposed to daily unstable housing conditions for the entire duration of the psychosocial stress regimen. The control group received stable (conventional) housing conditions and an equivalent amount of chamber exposure on Days 1, 11 and 32, without cat exposure. Behavioral testing commenced for all groups on Day 116. The stress groups demonstrated increased anxiety on the elevated plus maze, impaired object recognition memory and robust contextual and cued fear conditioned memory 3 months after the last conditioning session. Combined data from the two stress groups revealed lower post-stress corticosterone levels and greater diastolic blood pressure relative to the control group. These findings indicate that predator-based psychosocial stress produces persistent PTSD-like physiological and behavioral abnormalities that may provide insight into the neurobiological and endocrine sequelae in traumatized people with PTSD.