Psychosocial Stress in Rats: Animal Model of PTSD Based on Clinically Relevant Risk Factors

Abstract

A primary goal of research on the neurobiological basis of post-traumatic stress disorder (PTSD) is to understand how emotional trauma can produce persistent detrimental effects on behavior and brain functioning. The goals of this area of research are to provide insight into biomarkers of emotional trauma and to develop more effective pharmacotherapy for PTSD. To accomplish these goals, the design of translational research needs to link animal models of PTSD to clinically relevant risk factors which address one's resilience, as well as susceptibility, to develop persistent psychopathology in response to trauma. In the current review, we have discussed neurobiological and neuroendocrine aspects of PTSD and then briefly review the broad range of animal models of PTSD. We then discuss our psychosocial stress model of PTSD which is based on well-described PTSD-inducing risk factors, including a life-threatening experience, a sense of horror and uncontrollability, and an absence of social support and stability. Specifically, our psychosocial stress model integrates acute episodes of inescapable exposure of immobilized rats to a predator with chronic daily social instability. This stress regimen produces PTSD-like effects in rats at behavioral, cognitive, physiological, pharmacological, and genetic levels of analysis. Moreover, we also review our recent work that demonstrates greater evidence of neuroinflammation in rats exposed to the combination of psychological stress and physical (concussive) trauma. Overall, this translational approach has helped to bridge the gap between human and animal PTSD research and to create a framework for discovery of biomarkers of emotional trauma in clinical populations and toward the development of novel therapeutics for psychopathology.