Effects of Exercise Type and Sertraline on Anxiety and Social Behavior in a Female Rat Model of PTSD

Post-traumatic stress disorder (PTSD) often co-occurs with anxiety and social interaction difficulties, particularly in females. This study examined the effects of voluntary and involuntary exercise, combined with sertraline, on PTSD-like symptoms, anxiety, and social behavior in female rats.

PTSD-like symptoms were induced using the Single Prolonged Stress (SPS) model, which involved sequential exposure to restraint stress (2 h), forced swimming (20 min), and ether anesthesia (2-3 min), followed by a 7-day incubation period. A 10-min restraint was then applied as an additional stress event. Afterward, the rats underwent voluntary wheel running or treadmill exercise (5 days per week), with or without sertraline treatment (10 mg/kg/day) for 4 weeks. Behavioral assessments were conducted using the Elevated Plus Maze (EPM) and the Three-Chamber Social Test (3-CST). One day after behavioral testing, estrous cycles were evaluated using vaginal smears, followed by corticosterone analysis in blood samples the next day.

Involuntary exercise and sertraline significantly reduced anxiety-like behavior, with involuntary exercise showing a stronger effect than voluntary exercise. Involuntary exercise also improved sociability and social novelty, while sertraline enhanced social novelty. Notably, sertraline reduced corticosterone levels, with the greatest effect observed when combined with involuntary exercise.

These findings suggest that combining involuntary exercise with pharmacological treatment may provide synergistic benefits for alleviating anxiety-like behaviors and stress responses in a PTSD-like rat model.