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The role of medial prefrontal corticosterone and dopamine in the antidepressant-like effect of exercise

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Title: The role of medial prefrontal corticosterone and dopamine in the antidepressant-like effect of exercise
Authors: Chen, Chong Browse this author
Nakagawa, Shin Browse this author →KAKEN DB
Kitaichi, Yuji Browse this author →KAKEN DB
An, Yan Browse this author
Omiya, Yuki Browse this author
Song, Ning Browse this author
Koga, Minori Browse this author
Kato, Akiko Browse this author
Inoue, Takeshi Browse this author →KAKEN DB
Kusumi, Ichiro Browse this author →KAKEN DB
Keywords: Corticosterone
Medial prefrontal cortex
Issue Date: Jul-2016
Publisher: Elsevier
Journal Title: Psychoneuroendocrinology
Volume: 69
Start Page: 1
End Page: 9
Publisher DOI: 10.1016/j.psyneuen.2016.03.008
PMID: 27003115
Abstract: 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.
Rights: © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 中川 伸

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