PS253. Establishing a fear extinction-impaired animal model of post-traumatic stress disorder

Abstract

Abstract Post-traumatic stress disorder (PTSD), a common anxiety disorder, occurs less than 10 % of individuals after experiencing one or more terrifying accidents. One of key symptoms reported in PTSD patients is repeatedly and persistently re-experiencing the traumatic event due to the recurrent visits of fearful memory. The estimated lifetime prevalence of PTSD among adult Americans is 7.8 % while ∼60 % of adults reported to have experienced at least one traumatic event. Currently available animal models include physical and social stress models, however stressor models cannot distinguish general trauma coping responses from persistent and selective PTSD symptoms. Therefore, we took advantage of a genetic strain of mouse, 129S1/SvImJ (129S1) to establish a convincing animal model for PTSD. 129S1 has been reported to have a trouble with fear memory forgetting or fear extinction after fear conditioning. Here, we evaluated 129S1 as a bona-fide, fear extinction-impaired animal model for PTSD at cellular, synaptic and behavioral levels. 129S1 shows reduced immediate early gene, c-Fos expression in infralimbic cortex of medial prefrontal cortex and basolateral amygdala compared to C57BL/6, both of which are parts of fear extinction circuitry. We found that 129S1 had no problem in fear memory formation while having impaired fear extinction in both auditory and contextual fear conditioning protocols. 129S1 exhibited comparable hippocampal dependent spatial memory in Morris water maze following contextual fear conditioning compared to C57BL/6, suggesting that fear memory impairment is only selective to fear extinction in 129S1. Therefore we propose that 129S1 could serve as a useful animal model for PTSD to study the etiology and pathophysiology underlying PTSD.