A. M. CHOO1, S DAVIS1, M LANG1, A BARBOZA1, M OSBORNE1, Q CHANG1, T HANANIA1
1PsychoGenics Inc., Tarrytown, NY, USA
Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are often associated with each other. Comorbidity of TBI and PTSD are often seen in military populations. It is estimated that 35% of returning veterans suffer from both PTSD and TBI. Currently, there is no standardized preclinical model of PTSD with traumatic brain injury. We studied the development of PTSD behavioral phenotypes by combining two widely used preclinical models of PTSD and TBI: immobilization stress and controlled cortical impact in rats. Following 1 week of incubation after immobilization, stressed animals exhibited a significant increase in open arm entries and spent more time in the open arms of the elevated plus maze which was suggestive of an increase in risk-taking behavior. This risk-taking phenotype was observed to subside to similar levels as non-stressed controls by 2 weeks after immobilization. If instead, animals received TBI after immobilization stress, the risk-taking phenotype remained significantly elevated at this 2 week time point. In fear conditioning test, animals that received TBI-only showed similar freezing to non-stressed navie animals during tone and shock exposure. In contrast, animals that received only immobilization stress exhibited potentiated freezing during training while animals that received both immobilization stress and TBI exhibited less freezing. In the tone cue test, the group that received both immobilization stress and TBI again showed the lowest levels of freezing. These results suggest that the predominant phenotype of combined immobilization stress with controlled cortical impact brain injury is heightened activity and risk-seeking behavior during the sub-acute period following stress and TBI. This model may be useful for studying the evolution of preclinical stress-TBI phenotypes over time.