One of the most robust and sustained mechanisms involved in the exercise-induced antidepressant effect is the elevation of hippocampal brain-derived neurotrophic factor (BDNF) mRNA levels during voluntary exercise in normal rats (Oliff et al., 1998; Molteni et al., 2000) and also in an animal model of depression (Zheng et al., 2006). Here, BDNF is linked to major depressive disorder.