Lactate mediates in part the voluntary exercise-mediated induction of hippocampal Bdnf expression and promotion of learning. A, The exercise paradigm involves 4 weeks of voluntary exercise followed by animal death and hippocampal isolation. B, Voluntary exercise for 4 weeks significantly increases hippocampal lactate levels. The number of hippocampi used for each group (control and exercise) is 10 and 9, respectively. **p < 0.01 (unpaired t test; p = 0.0366 and df = 17). C, Voluntary exercise significantly induces Bdnf promoter I expression in the hippocampus as measured by real-time RT-PCR, whereas inhibiting the lactate MCT transporters by AR-C155858 (50 nm/mouse) abolishes this induction. The number of hippocampi used for each group (control, exercise, and exercise + AR-C155858) is 5, 2, and 4, respectively.**p < 0.01 (one-way ANOVA followed by Dunnett's multiple-comparison test; p = 0.001 for exercise vs control and p = 0.4778 for exercise + AR-C155858 vs control). D, Voluntary exercise does not induce Bdnf pIV or coding expression in the hippocampus as measured by real-time RT-PCR.