The Antidepressant-like Effect of Physical Activity on a Voluntary Running Wheel

CUNHA, M. P., A. OLIVEIRA, F. L. PAZINI, D. G. MACHADO, L. E. B. BETTIO, J. BUDNI, A. S. AGUIAR JR, D. F. MARTINS, A. R. S. SANTOS, and A. L. RODRIGUES. The Antidepressant-like Effect of Physical Activity on a Voluntary Running Wheel. Med. Sci. Sports Exerc., Vol. 45, No. 5, pp. 851-859, 2013. Purpose: Physical activity is currently being considered an effective alternative in the treatment of depression. At the preclinical level, the voluntary running wheel is a useful method of increasing physical activity in rodents and induces an antidepressant-like effect in some behavioral paradigms. Methods: This study investigated the effect of physical activity on a voluntary running wheel in mice submitted to the forced swimming test (FST) and tail suspension test, two predictive tests of antidepressant properties. Moreover, the influence of the inhibition of serotonin and noradrenaline synthesis as well as the inhibition of protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CAMK-II) activity by pharmacological agents in the antidepressant-like action of physical activity was investigated. Results: Physical activity on a voluntary running wheel by 21 d produced a reduction in the immobility time in the FST and tail suspension test, without producing alteration on locomotor activity in the open-field test. The antidepressant-like effect in the FST elicited by physical activity lasted for 7 d after removal of the running wheel. The anti-immobility effect of physical activity was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (100 mg.kg(-1), i.p., once a day, for four consecutive days, inhibitor of serotonin synthesis), alpha-methyl-p-tyrosine (100 mg.kg(-1), i.p., an inhibitor of noradrenaline and dopamine synthesis), H-89 (1 mu g per site, i.c.v., a PKA inhibitor), and KN-62 (1 mu g per site, i.c.v., a CAMK-II inhibitor). Conclusions: Taken together, these results first suggest that the effect of physical activity on the FST is dependent on either the increase in the bioavailability of monoamines in the synaptic cleft or an activation of intracellular signaling pathways mediated by PKA and CAMK-II.