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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 | Depression | Dopamine | Exercise | Medial prefrontal cortex | Stress |
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 http://creativecommons.org/licenses/by-nc-nd/4.0/ | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/66416 |
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)
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Submitter: 中川 伸
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