Short-Term But Not Long Term Exercise Ameliorates Depressive Behavior in Mice

Objective Voluntary exercise has been reported to reduce depression- and anxiety-like behaviors in an animal model of depressive disorder (DD). However, the degree of appropriate voluntary exercise to improve depression-like behavior remains unknown. In the present study, we examined the effects of two different terms of voluntary exercise, short (3 days)- and long (14 days)-term freewheel running, on depression-like behavior and new cell proliferation in the dentate gyrus (DG) in a DD mouse model generated by exposure to chronic mild stress (CMS), and then compared the antidepressant effects with those of ketamine. Methods Freewheel running was used as the voluntary exercise. DD model mice, which were generated by subjecting mice to CMS for 4 weeks (CMS mice), were allowed free access to a running wheel for 3 or 14 days. Next, we examined the effects of voluntary freewheel running and ketamine on depression-like behavior in CMS mice using the forced-swim test (FST). New cell proliferation in the DG of the hippocampus was immunohistochemically analyzed by enumerating the number of 5-bromo-2’-deoxyuridine (BrdU)-labeled cells following administration of BrdU (100 mg/kg, twice a day for 3 days). Results Short-term freewheel running showed an antidepressant effect in CMS mice in the FST, which was comparable to that of ketamine, but did not affect new cell proliferation in the DG. In contrast, long-term freewheel running increased new cell proliferation in the DG, but did not improve depressive behavior in the FST. Conclusion Short-term but not long-term voluntary exercise in CMS mice resulted in improvement of depression- like behavior similar to antidepressant ketamine, and appeared to be independent of exercise-induced stimulation of new cell proliferation in the DG.