Physical activity-antidepressant treatment combination: impact on brain-derived neurotrophic factor and behavior in an animal model

The mechanism of antidepressant action, at the cellular level, is not clear ly understood. It has been reported that chronic antidepressant treatment l eads to an up-regulation of brain-derived neurotrophic factor (BDNF) mRNA l evels in the hippocampus, and that physical activity (voluntary running) en hances this effect. We wished to investigate whether BDNF expression brough t about by these interventions may overcome deficits caused by acute stress , and might impact behavior in an animal model. In this report, we have tes ted the hypothesis that the combination of the antidepressant, tranylcyprom ine, and physical exercise could lead to decreased neurotrophin deficits an d enhanced swimming time in animals that have been forced to swim in an ine scapable water tank. Rats were either treated with tranylcypromine, engaged in voluntary running, or both for one week. After these treatments, the an imals underwent a two-day forced swimming procedure. BDNF mRNA levels were significantly depressed in untreated animals subjected to forced swimming. Animals that either underwent prior activity or received antidepressant sho wed BDNF mRNA levels restored to baseline. Animals receiving the combined i ntervention showed an increase in hippocampal BDNF mRNA well above baseline . Swimming time during a five-minute test was significantly enhanced in ani mals receiving the combined intervention over untreated animals. Swimming t ime was not significantly enhanced over that of animals receiving antidepre ssant alone, however. Enhanced swimming time correlated with increased leve ls of BDNF mRNA in one hippocampal sub-region (CA4-hilus). These results su ggest that the combination of exercise and antidepressant treatment may hav e significant neurochemical, and possibly behavioral, effects. In addition, these results support the possibility that the enhancement of BDNF express ion may be an important element in the clinical response to antidepressant treatment. The induction of BDNF expression by activity/pharmacological tre atment combinations could represent an important intervention for further s tudy, to potentially improve depression treatment and management. (C) 2001 Elsevier Science B.V. All rights reserved.