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

Abstract

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.

Elevated dopamine signaling from ventral tegmental area to prefrontal cortical parvalbumin neurons drives conditioned inhibition

“…In a single prolonged stress (SPS) model of PTSD (Fig. 7A) (40), we found a significant increase in freezing level during CS− (Fig. 7B) and a low discrimination index (Fig.…”

“…Deficits in SL/fear discriminating have been found in certain psychiatric disorders, especially anxiety disorders, and has been proposed as a biomarker (11,53,54). Defective DA signaling has been implicated in PTSD, including deficits in the reward and reinforcement circuits, decreased reward anticipation and reduced hedonic responses, reduced DA metabolites in cerebral spinal fluid following traumatic reminders, altered expression of striatal DA transporter, and polymorphisms in genes encoding DAT and DA receptors in PTSD patients (40). A reduced basal spiking rate of VTA DA neurons (55) and altered DA level (56) were reported in PTSD models.…”

Silymarin Prevents Memory Impairments, Anxiety, and Depressive-Like Symptoms in a Rat Model of Post-Traumatic Stress Disorder

“…Future direction to build on this study would be to explore the beneficial effects of silymarin in female rats. Notably, the induction of PTSD like behavior in animals has been a challenge [35]. PTSD is a complex disorder to be apprehended in a well-val-idated rat model.…”

New neurons restore structural and behavioral abnormalities in a rat model of PTSD

“…A single-prolonged stress (SPS) protocol using three different stressors in the course of one day mimics neurochemical and behavioral effects of PTSD in rodents (Liberzon, Krstov, & Young, 1997;Lisieski, Eagle, Conti, Liberzon, & Perrine, 2018;Richter-Levin, Stork, & Schmidt, 2018). SPS causes abnormalities in glucocorticoid receptor expression, activation of the HPA axis, and excitatory and inhibitory neurotransmitter levels in the hippocampus after an incubation period of 1 week following stress (Liberzon et al, 1997;Yamamoto et al, 2009).…”