Effects of Moderate Treadmill Exercise and Fluoxetine on Spatial Memory, Anxiety, and Positive Tunnel Cells in the Hippocampus in a Rat Model of PTSD

 Background and purpose: Post-traumatic stress disorder (PTSD) is a condition that develops after experiencing major trauma. Selective serotonin reuptake inhibitors (SSRIs) are first-line treatment for PTSD. This study aimed at investigating the effects of moderate treadmill exercise and fluoxetine on anxiety, spatial memory, and positive tunnel cells in the hippocampus in a rat model of PTSD. Materials and methods: We used single prolonged stress (SPS) model as an animal model for PTSD. Male and female rats were divided into two groups: Sham and SPS. After Two weeks, interventions, including treadmill exercise (4 weeks, 5 days per week), fluoxetine (10 mg/kg/day), and combined treatment were performed. Then, anxiety and memory test and tunnel assessments were done. Results: SPS rats exhibited increased anxiety levels in light/dark box and enhanced hippocampal apoptotic cells. Male SPS rats showed impaired spatial memory in object-location memory task. Treadmill exercise, fluoxetine, and combined treatment reduced anxiety levels, improved spatial memory, and decreased positive tunnel cells in the hippocampus. Furthermore, combined treatment with fluoxetine and treadmill exercise was found to be more effective than fluoxetine alone. Female rats had more resilience than male rats. Conclusion: Combined intervention with moderate exercise and fluoxetine is more useful in treatment of behavioral and cellular injuries in PTSD patients.