Accumulating evidence indicates that physical exercise can reduce or prevent the incidence of stress-related psychiatric disorders, including depression. Several studies have suggested that physical exercise produces its antidepressant effects by mediating activation of serotonin (5-HT) neurons in the dorsal raphe nuclei (DRN) and corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN). Recently, we investigated the effects of a bout of 30-min treadmill running at different intensities on activities of these neurons, and depressive-like behavior in rats, and suggested that acute low-intensity (sub-lactate threshold) exercise activates DRN 5-HT neurons without producing high activation of PVN CRF neurons, and can effectively induce antidepressant properties. On the other hand, some studies, using in vivo microdialysis, reported that acute exercise increased the levels of 5-HT in a time-dependent manner. It is, thus, possible that the effects of acute exercise on neuronal activation and behaviors depend on duration and intensity of exercise. In the present study, we examined activity of DRN 5-HT neurons and PVN CRF neurons during treadmill running at different intensities (control, 0 m/min; low speed, 15 m/min; high speed, 25 m/min) with different duration (15 min, 30 min, 60 min) in male Wistar rats, using c-Fos/5-HT or CRF immunohistochemistry. We also performed a forced swim test to assess depressive-like behavior. Acute treadmill running at low speed increased c-Fos expression of DRN 5-HT neurons regardless of exercise duration, compared to the control, whereas the high-speed running activated DRN 5-HT neurons only with 60-min duration. On the other hand, c-Fos expression of PVN CRF neurons was enhanced in a manner that depended on exercise intensity, regardless of exercise duration. Furthermore, low-speed running with 30- and 60-min duration decreased depressive-like behavior compared to the control. In addition, the high-speed running decreased the depressive-like behavior only with 60-min duration. These results suggest that effects of acute treadmill running on the behavior and neuronal activation involved in the antidepressant property depend on duration and intensity of exercise.

研究助成：Research funds : KAKENHI JP 16K13017