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Regular exercise is acknowledged for its wide-ranging benefits to brain health, including mood improvement and protection against age-related cognitive decline and neurodegenerative diseases. As for long-term exercise training, a growing body of research also suggests a significant influence of a single bout of exercise, termed “acute exercise”, on brain function, including enhancement of emotional states and stress coping. In the context of exercise, the most widely studied brain region is arguably the hippocampus, but running wheel exercise in rodents coincides with neuronal activity in a long list of brain regions, including the hypothalamus, several striatal regions, the somatosensory cortex, the medial prefrontal cortex, and the motor-coordinating red nucleus of the midbrain. Thus, not surprisingly, endurance exercise in rodents has been linked to pleiotropic central effects including effects on appetite, reward, pain, locomotion, and proprioception. Insights into the impact of exercise on the brain have largely been derived from studies conducted on rats or mice, utilizing two commonly employed exercise paradigms: forced treadmill running and voluntary wheel running. While forced treadmill running offers control over exercise intensity and duration, it has been implied to be a stressful paradigm. Both male and female rats exhibit increased plasma corticosterone levels in response to treadmill running. Accordingly, phenotypic changes resulting from forced treadmill running may be attributed not only to exercise itself but also to the added stress. Running wheels, in contrast, are often viewed as an environmental enrichment and rodents voluntarily engage with running wheels to run distances of 4–8 km each night, depending on strain and sex. This underscores that running wheels provide an opportunity for mice and rats to engage in regular exercise, and that this activity is remarkably rewarding for the animals. Despite the substantial differences between these two endurance exercise interventions, they are often interchangeably utilized in the literature. This is potentially problematic, and the stressful aspects of forced treadmill running might limit the predictable value of this intervention for mimicking human exercise.

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