Single-Prolonged Stress: A Review of Two Decades of Progress in a Rodent Model of Post-traumatic Stress Disorder

Michael J. Lisieski, Andrew L. Eagle, Alana C. Conti, Israel Liberzon, Shane A. Perrine

Post-traumatic stress disorder (PTSD) is a common, costly, and often debilitating psychiatric condition. However, the biological mechanisms underlying this disease are still largely unknown or poorly understood. Considerable evidence indicates that PTSD results from dysfunction in highly-conserved brain systems involved in stress, anxiety, fear, and reward. Pre-clinical models of traumatic stress exposure are critical in defining the neurobiological mechanisms of PTSD, which will ultimately aid in the development of new treatments for PTSD. Single prolonged stress (SPS) is a pre-clinical model that displays behavioral, molecular, and physiological alterations that recapitulate many of the same alterations observed in PTSD, illustrating its validity and giving it utility as a model for investigating post-traumatic adaptations and pre-trauma risk and protective factors. In this manuscript, we review the present state of research using the SPS model, with the goals of (1) describing the utility of the SPS model as a tool for investigating post-trauma adaptations, (2) relating findings using the SPS model to findings in patients with PTSD, and (3) indicating research gaps and strategies to address them in order to improve our understanding of the pathophysiology of PTSD.