Difference in the brain serotonin and its metabolite level and anxiety-like behavior between forced and voluntary exercise conditions in rats.

Physical exercise is beneficial to both physical and mental health, though it is unclear whether voluntary and forced exercise have the same effects. We investigated the effects of chronic forced and voluntary wheel running on brain levels of serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5-HIAA), and anxiety-like behavioral change in rats. Forty-eight rats were randomly assigned to standard cages (sedentary control: SC); voluntary exercise (free running on a wheel, V-EX); voluntary limited exercise (wheel available only 1 h per day, VL-EX); and forced exercise (running on a motorized wheel, F-EX). After 4 weeks, rats either underwent the open field test (OFT) or their 5-HT and 5-HIAA levels were measured in the major serotonergic neural cell bodies and projection areas. 5-HT and 5-HIAA levels in the dorsal and median raphe nuclei were increased in the V-EX, but not in the VL-EX and F-EX groups, compared with the SC group. In the paraventricular hypothalamic nucleus and caudate putamen, only 5-HT levels were increased in the V-EX group. Interestingly, in the amygdala, only 5-HIAA levels were significantly increased in the V-EX group. Conversely, we found that F-EX rats showed no significant 5-HT changes and increased anxiety-like behavior. VL-EX did not have significant beneficial effects on any of the experimental parameters. These data suggest that only unlimited voluntary exercise stimulates the serotonergic system and suppresses anxiety-like behavior.