Spinosin ameliorates post-traumatic stress disorder-like behaviors via 5-HT_1A receptor in mice

Post-traumatic stress disorder (PTSD) is a severe mental illness characterized by increased arousal, intrusion, avoidance, and negative cognitive alterations following exposure to fatal stresses or psychological trauma. In this study, we explored the ameliorating effects of spinosin on PTSD-like behaviors in PTSD model mice induced by single prolonged stress (SPS). A single dose of spinosin (3 mg/kg, p.o.) ameliorated PTSD-like behaviors as assessed using the elevated plus-maze test, marble burying test, Y-maze test, tail suspension test, and fear extinction test. Furthermore, we discovered that spinosin promotes fear extinction through 5-HT_1A receptor activation. We also verified that spinosin normalizes the increased phosphorylation levels of PKA and CREB, which are downstream signaling pathways of the 5-HT_1A receptor, in the amygdala of mice modeling PTSD. Our findings suggest that spinosin could be an effective treatment for PTSD via 5-HT_1A receptor activation, addressing the limitations of current PTSD medications.