Voluntary exercise produces antidepressant and anxiolytic behavioral effects in mice

Abstract

Reports of beneficial effects of exercise on psychological health in humans are increasingly supported by basic research studies. Exercise is hypothesized to regulate antidepressant-related mechanisms and we therefore characterized the effects of chronic exercise in mouse behavioral paradigms relevant to antidepressant actions. Mice given free access to running wheels showed antidepressant-like behavior in learned helplessness, forced-swim (FST) and tail suspension paradigms. These responses were similar to responses of antidepressant drug-treated animals. When tested under conditions where locomotor activity was not altered, exercising mice also showed reduced anxiety compared to sedentary control mice. In situ hybridization analysis showed that BDNF mRNA was increased in specific subfields of hippocampus after wheel running. We chose one paradigm, the FST, in which to investigate a functional role for brain-derived neurotrophic factor (BDNF) in the behavioral response to exercise. We tested mice heterozygous for a deletion of the BDNF gene in the FST after wheel-running. Exercising wild-type mice showed the expected antidepressant-like behavioral response in the FST but exercise was ineffective in improving FST performance in heterozygous BDNF knockout mice. A possible functional contribution of a BDNF signaling pathway to FST performance in exercising mice was investigated using the specific MEK inhibitor PD184161 to block the MAPK signaling pathway. Subchronic administration of PD184161 to exercising mice blocked the antidepressant-like behavioral response seen in vehicle-treated exercising mice in the FST. In summary, chronic wheel-running exercise in mice results in antidepressant-like behavioral changes that may involve a BDNF related mechanism similar to that hypothesized for antidepressant drug treatment.

Voluntary wheel running ameliorates symptoms of MK-801-induced schizophrenia in mice

“…The enhancement effect of physical exercise on hippocampal BDNF expression has been consistently reported in previous studies (36,46,47). Enhanced BDNF expression in the hippocampus via exercise inhibits age-induced deterioration of short-term and spatial working memories (33).…”

Are Voluntary Wheel Running and Open-Field Behavior Correlated in Mice? Different Answers from Comparative and Artificial Selection Approaches

“…Several environmental factors might have contributed to differences among those studies (e.g., the level of physical activity and housing conditions). Duman et al (2008) speculated that reduced locomotion in the open-field that was possibly related to immediate fatigue after running (see also Fuss et al 2010). This seems unlikely to us, however, as even our HR mice do not run voluntarily on wheels at speeds that exceed their maximal aerobic capacity Rezende et al 2005), nor do they show obvious signs of fatigue during or following wheel running (Meek et al 2009;personal observations).…”

“…It has been shown that intense physical activity subsequently alters behavior in the open-field, but the results are inconsistent, ranging from reduced (Duman et al 2008;Fuss et al 2010), unaffected (Leasure and Jones 2008), to increased locomotion (Burghardt et al 2004) in rodents after voluntary wheel running. Several environmental factors might have contributed to differences among those studies (e.g., the level of physical activity and housing conditions).…”

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

“…Interestingly, an interaction of antidepressant treatment effects and elevated expression of neurotrophic factors is not limited to pharmacological manipulation. Voluntary exercise was suggested to have antidepressant properties in animal models (Duman et al 2008) and mood-elevating actions in humans (Babyak et al 2000). A recent microarray study showed that also voluntary exercise up-regulated several neurotrophic factors (Hunsberger et al 2007).…”