Comparative effects of voluntary and forced exercise on cognitive performance, thyroid function, and hippocampal integrity in a rat model of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is associated with cognitive impairments, neuroendocrine dysregulation, and hippocampal neuronal loss. Although exercise has shown therapeutic potential in stress-related conditions, comparative evidence on voluntary versus forced exercise modalities in animal models of PTSD remains limited. This study evaluated the effects of voluntary (running wheel, RW) and forced (treadmill running, TR) exercise on cognitive performance, thyroid function, and hippocampal integrity in a rat model of PTSD induced by single prolonged stress (SPS). Male Wistar rats were randomly assigned to non-stressed or SPS-exposed groups, each further subdivided into sedentary, voluntary exercise, or forced exercise subgroups (n = 7 per group). Cognitive performance was assessed using the Object Location Memory Test and Object Recognition Memory Test. Serum levels of T3, T4 and TSH were measured using ELISA kits. Hippocampal neuronal density was evaluated via hematoxylin and eosin staining. SPS exposure significantly impaired spatial and recognition memory, disrupted thyroid hormone profiles (decreased T3 and T4, increased TSH), and reduced hippocampal neuronal density in sedentary rats. Both RW and TR interventions improved cognitive function, normalized thyroid hormone levels, and preserved hippocampal structure. Notably, voluntary exercise produced greater improvements in memory performance and endocrine recovery compared to forced exercise. Both voluntary and forced exercise alleviate cognitive, hormonal, and structural impairments in a rat model of PTSD, with voluntary exercise demonstrating superior therapeutic efficacy. These findings highlight the potential of physical activity, particularly self-directed, voluntary modalities, as a promising non-pharmacological strategy for mitigating the neurobiological consequences of traumatic stress.