Voluntary versus forced exercise modulates anxiety‑like behaviors and hippocampal inflammation gene expression following traumatic stress in rats

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Background: Post-traumatic stress disorder (PTSD) arises after traumatic or life-threatening events and involves persistent anxiety and altered stress responses. Physical exercise is a proposed non-pharmacological intervention, yet evidence comparing voluntary and forced exercise regarding their behavioral and biochemical effects in experimental PTSD models is still limited. Methods: In this experimental study, adult male rats were subjected to a single prolonged stress (SPS) protocol to induce a PTSD-like phenotype and were subsequently assigned to voluntary exercise, forced exercise, or control conditions. Anxiety-like behaviors were evaluated using behavioral tests, including the open field test, elevated plus maze, and light-dark box. The hippocampal mRNA expression levels of inflammatory cytokines, including IL-1β, IL‑10, and TNF‑α, were quantified by reverse transcription polymerase chain reaction. Results: Exposure to SPS induced a marked anxiety‑like behavioral phenotype, as evidenced by reduced exploration of anxiogenic zones across all behavioral paradigms, without significantly affecting general locomotor activity. SPS exposure was also associated with increased hippocampal expression of the pro‑inflammatory cytokines IL‑1β and TNF‑α, accompanied by reduced expression of the anti‑inflammatory cytokine IL‑10. Both voluntary and forced exercise attenuated SPS-induced anxiety-like behaviors and significantly improved hippocampal inflammatory gene expression. Voluntary exercise produced greater improvement across several behavioral measures. At the molecular level, both exercise modalities attenuated SPS-induced pro-inflammatory alterations, whereas voluntary exercise alone significantly restored the anti-inflammatory cytokine IL-10. Conclusion: Both voluntary and forced exercise effectively attenuated SPS-induced anxiety-like behavior and hippocampal inflammatory dysregulation. Voluntary exercise demonstrated greater behavioral improvement across anxiety-related paradigms. Although only the VolExc group reached statistical significance relative to the SPS group for IL-10, direct comparison between VolExc and ForExc did not reveal a significant difference, indicating that molecular outcomes were broadly comparable between the two exercise modalities. These findings suggest that voluntary exercise may provide behavioral advantages following traumatic stress, although the two modalities were not statistically distinguishable from one another at the molecular level.

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