Chronic running-wheel exercise from adolescence leads to increased anxiety and depression-like phenotypes in adulthood in rats: Effects on stress markers and interaction with BDNF Val66Met genotype.

Exercise has been shown to be beneficial in reducing symptoms of affective disorders and to increase the expression of brain-derived neurotrophic factor (BDNF). The BDNF Val66Met polymorphism is associated with reduced activity-dependent BDNF release and increased risk for anxiety and depression. Male and female Val66Met rats were given access to running wheels from 3 weeks of age and compared to sedentary controls. Anxiety- and depression-like behaviors were measured in adulthood using the elevated plus maze (EPM), open field (OF), and forced swim test (FST). Expression of BDNF and a number of stress-related genes, the glucocorticoid receptor (Nr3c1), serum/glucocorticoid-regulated kinase 1 (Sgk1), and FK506 binding protein 51 (Fkbp5) in the hippocampus were also measured. Rats given access to running wheels developed high levels of voluntary exercise, decreased open-arm time on the EPM and center-field time in the OF, reduced overall exploratory activity in the open field, and increased immobility time in the FST with no differences between genotypes. Chronic exercise induced a significant increase in Bdnf mRNA and BDNF protein levels in the hippocampus with some of these effects being genotype specific. Exercise decreased the expression of Nr3c1 and Sgk1, but increased the expression of Fkbp5. These results suggest that chronic running-wheel exercise from adolescence increased anxiety and depression-like phenotypes in adulthood, independent of BDNF Val66Met genotype. Further studies are required to confirm that increased indices of anxiety-like behavior are independent from reduced overall locomotor activity.