Use of Single Prolonged Stress to Model Post-traumatic Stress Disorder inRodents: What We Found and Where to Next?

Abstract: Post-traumatic stress disorder (PTSD) represents a grave and expansive mental illness, caused by experiencing or witnessing traumatic events that invoke profound feelings of helplessness, fear and anxiety. Reflecting the clinical features of PTSD, the single prolonged stress (SPS) model in rodents was developed to elucidate the pathogenesis and identify potential therapeutic interventions. This review aimed to deepen our understanding of the mechanisms and therapeutic methods for PTSD. We conducted a comprehensive literature search on PubMed and Web of Science using keywords such as "SPS", "PTSD", and "mechanisms". Clinical and animal research, especially the exploration of the mechanisms and treatments, were included in this review. We identified a total of 327 articles. After removing duplicates and screening the full texts, we selected only 137 articles. Based on the literature, we examined the parallels and divergences between PTSD and the SPS model regarding symptomatic manifestations, affected brain regions, and molecular markers, demonstrating that the SPS model can effectively replicate PTSD-like behaviors in rodents. Guided by clinical research findings, we further synthesized the mechanisms by which SPS induces PTSD, focusing on the modulation of relevant signaling pathways and neural circuits. Additionally, we reviewed potential intervention strategies for PTSD using this model, encompassing both pharmacological and nonpharmacological therapies. This review offers significant implications for basic research rooted in the clinical characteristics of PTSD, suggesting that studies utilizing the SPS model could enhance our understanding of PTSD and aid in the identification of effective treatment strategies.