The glucocorticoid system is required for the voluntary exercise-induced enhancement of learning and memory in rats.

Although it is well established that voluntary exercise can improve cognitive functions, the underlying mechanisms are largely unknown. Glucocorticoids play an important role in learning and memory functions. This study addressed whether the glucocorticoid system would play a role in the exercise-induced enhancement of learning and memory. Intact rats or those that were either adrenalectomized or daily given the corticosterone-synthesis inhibitor metyrapone were allowed to freely exercise in a running wheel for 10 days. Control animals were kept sedentary for this period. After this period, they were trained and tested on a water-maze spatial task using three-trial per day for 5 consecutive days, succeeded by a probe trial two days later. Exercise increased plasma corticosterone levels, as assessed after this 10-day period. Both adrenalectomy and metyrapone slightly reduced running-wheel activity. Adrenalectomy reduced the plasma corticosterone levels to almost zero whereas metyrapone selectively blocked the exercise-induced increase in corticosterone levels. Exercise significantly improved performance during both training and retention of the water-maze task whereas this effect was absent in both adrenalectomized and metyrapone-treated rats. These findings indicate that the glucocorticoid system play a crucial role in the beneficial effects of voluntary exercise on cognitive functions in rats.