期刊
PSYCHONEUROENDOCRINOLOGY
卷 69, 期 -, 页码 1-9出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.psyneuen.2016.03.008
关键词
Corticosterone; Depression; Dopamine; Exercise; Medial prefrontal cortex; Stress
资金
- Japanese Ministry of Education, Culture, Sports, Science and Technology [23591667]
- Hokkaido University Clark Memorial Foundation
- Grants-in-Aid for Scientific Research [23591667] Funding Source: KAKEN
Despite the well-documented beneficial effect of exercise on stress coping and depression treatment, its underlying neurobiological mechanism remains unclear. This is further complicated by a 'side effect' of exercise: it increases basal glucocorticoid (CURT), the stress hormone, which has been shown to be a mediator linking stress to depressive disorders. Here we show that three weeks of voluntary wheel running reduced rats' immobility in the forced swim test (FST), an antidepressant-like effect. Monitoring extracellular fluids in the medial prefrontal cortex PFC (mPFC) using microdialysis we found that, wheel running was associated with higher baseline CORT, but lower FST-responsive CORT. Further, wheel running resulted in a higher dopamine (DA) both at baseline and following FST. Interestingly, the antidepressant-like effect of wheel running was completely abolished by intra-mPFC pre-microinjection of a D2R (haloperidol) but not D1R (SCH23390) antagonist, at a dose that does not affect normal rats' performance in the FST. It suggests that exercise exerts antidepressant-like effect through upregulated DA and in a D2R dependent way in the mPFC. Importantly, the antidepressant-like effect of wheel running was also abolished by intra-mPFC pre-microinjection of a GR antagonist (RU486). Finally, intra-mPFC pre-microinjection of RU486 also downregulated the originally elevated basal and FST-responsive DA in the mPFC of exercise rats. These results suggest a causal pathway linking CURT, GR, DA, and D2R, to the antidepressant-like effect of exercise. In conclusion, exercise achieves antidepressant-like effect through the CORT-GR-DA-D2R pathway and that the increased basal CORT by exercise itself may be beneficial rather than detrimental. (C) 2016 Elsevier Ltd. All rights reserved.
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