Objective: The present study aimed to compare the effects of voluntary and forced exercise with caffeine supplementation on anxiety behaviors and oxytocin hormone levels in the brains of chronically stressed mice.
Materials and Methods: In this study, 35 male C57/BL-6 mice were randomly divided into five groups: control, stress, stress+caffeine, stress+caffeine+voluntary exercise, stress+caffeine+forced exercise. Chronic stress was induced for four weeks using the UCMS protocol. Voluntary or forced exercise was performed using a running wheel, and caffeine was injected intraperitoneally at a dose of 3 mg/kg. Intervention was performed four weeks before stress induction and four weeks after stress induction. The dark-light test was used to measure anxiety, and the ELISA kit was used to measure oxytocin levels. Data were analyzed using ANOVA and Tukey's post hoc test.
Findings: According to the results, chronic stress led to a significant increase in anxiety and a decrease in oxytocin levels in the brain(P=0.001). Caffeine consumption alone or combined with forced exercise had no significant effect on the number of entries into the light box and oxytocin levels(p>0.05). In contrast, caffeine consumption combined with voluntary exercise significantly reduced anxiety-related behaviors and increased brain oxytocin levels compared to other groups(p=0.001).
Conclusion: According to the results, voluntary exercise combined with caffeine consumption can be considered as an effective non-pharmacological intervention for reducing anxiety-related behaviors and increasing oxytocin levels in conditions of chronic stress. The choice of exercise type(voluntary or forced) plays a key role in the psychosocial and neurochemical effectiveness of interventions.