Using the Single Prolonged Stress Model to Examine the Pathophysiology of PTSD

Abstract

The endurance of memories of emotionally arousing events serves the adaptive role of minimizing future exposure to danger and reinforcing rewarding behaviors. However, following a traumatic event, a subset of individuals suffers from persistent pathological symptoms such as those seen in posttraumatic stress disorder (PTSD). Despite the availability of pharmacological treatments and evidence-based cognitive behavioral therapy, a considerable number of PTSD patients do not respond to the treatment, or show partial remission and relapse of the symptoms. In controlled laboratory studies, PTSD patients show deficient ability to extinguish conditioned fear. Failure to extinguish learned fear could be responsible for the persistence of PTSD symptoms such as elevated anxiety, arousal, and avoidance. It may also explain the high non-response and dropout rates seen during treatment. Animal models are useful for understanding the pathophysiology of the disorder and the development of new treatments. This review examines studies in a rodent model of PTSD with the goal of identifying behavioral and physiological factors that predispose individuals to PTSD symptoms. Single prolonged stress (SPS) is a frequently used rat model of PTSD that involves exposure to several successive stressors. SPS rats show PTSD-like symptoms, including impaired extinction of conditioned fear. Since its development by the Liberzon lab in 1997, the SPS model has been referred to by more than 200 published papers. Here we consider the findings of these studies and unresolved questions that may be investigated using the model.

Emotional remodeling with oxytocin durably rescues trauma-induced behavioral and neuro-morphological changes in rats: a promising treatment for PTSD

“…Regarding fear symptoms, vulnerable rats showed intense freezing when exposed to SPS-related cues during a period extending from 29 to 54 days post-trauma. The robustness and persistence of these symptoms confirm the validity of SPS as a PTSD model 36,37 .…”

Combined brain‐derived neurotrophic factor with extinction training alleviate impaired fear extinction in an animal model of post‐traumatic stress disorder

“…20,21 For instance, SPS rats exhibit enhanced glucocorticoid negative feedback, 22 sleep abnormalities, 23 enhanced anxiety, 24-26 hyperarousal 27 and enhanced contextual freezing 28 as well as the expected therapeutic response to long-term treatment with paroxetine on enhanced fear memory. SPS mimics many aspects of the pathophysiological abnormalities associated with PTSD, and also some aspects of the behavioral characteristics.…”

“…SPS mimics many aspects of the pathophysiological abnormalities associated with PTSD, and also some aspects of the behavioral characteristics. 20,21 For instance, SPS rats exhibit enhanced glucocorticoid negative feedback, 22 sleep abnormalities, 23 enhanced anxiety, [24][25][26] hyperarousal 27 and enhanced contextual freezing 28 as well as the expected therapeutic response to long-term treatment with paroxetine on enhanced fear memory. 29 Several studies have showed impaired fear extinction in SPS rats, 30,31 which is alleviated by repeated administration of D-cycloserine 32 or by single administration of vorinostat, a histone deacetylase inhibitor.…”

Gait and Conditioned Fear Impairments in a Mouse Model of Comorbid TBI and PTSD

“…Each SPS cohort began at 0800 h and ended with individual housing at 1300 h. Mice that were not randomized to SPS remained group housed for the duration of seven days that their counterparts underwent social isolation. Social isolation is a key component of SPS, and it has been shown to be a necessary incubation period for this trauma model [ 14 , 17 ].…”