Studying neural mechanisms of stress resilience in a novel animal model of PTSD

In a PTSD rat model we have developed, we utilize a novel behavioral profiling approach that allows the classification of affected and unaffected individuals in a trauma-exposed population. Other aspects of the model that increase its ecological validity to PTSD include:

a. Employing a brief, acute and intense, ecologically relevant trauma, relevant to the military context.

b. Examining the effects one month after trauma exposure, as in the diagnosis of PTSD.

c. Effects intensified by presentation of a reminder of the original trauma, as in human patients.

d. The inclusion of risk factors that contribute to developing PTSD, as in human subjects.

Rats were exposed to underwater trauma (UWT) and four weeks later their individual performances in the open field and elevated plus maze were compared to those of the control group, allowing the identification of affected and resilient UWT-exposed rats. Behavioral profiling revealed that only a subset of the UWT-exposed rats developed long-lasting behavioral symptoms. The proportion of affected rats was further enhanced by pre-exposure to childhood stress, a well described risk factor of PTSD.

Many studies suggest that alterations in GABA functioning are associated with stress and trauma. For a biochemical proof of concept of the behavioral profiling approach we have developed we analyzed the expression levels of the GABAA receptor subunits α1 and α2 in the ventral, dorsal hippocampus and baso-lateral amygdala. Increased expression, mainly of α1, was observed in ventral but not dorsal hippocampus of exposed animals, which would traditionally be interpreted as being associated with the exposure-resultant psychopathology.

However, behavioral profiling revealed that this increased expression was confined to exposed-unaffected individuals, suggesting a resilience-associated expression regulation. The results provide evidence for the importance of employing behavioral profiling in animal models of PTSD, in order to better understand the neural basis of stress vulnerability and stress resilience.

_{Supported by: A DOD USAMRMC Award Number W81XWH-11-2-0111 to GRL.}