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

PSYCHONEUROENDOCRINOLOGY

卷:69

Article

Chen, Chong¹  Nakagawa, Shin¹  Kitaichi, Yuji¹  An, Yan¹  Omiya, Yuki¹  Song, Ning^1,2  Koga, Minori¹  Kato, Akiko¹  Inoue, Takeshi³  Kusumi, Ichiro¹ 

[1] Hokkaido Univ, Grad Sch Med, Dept Psychiat, Sapporo, Hokkaido 0608638, Japan

[2] China Med Univ, Hosp 1, Dept Psychiat, Shenyang 110001, Peoples R China

[3] Tokyo Med Univ, Dept Psychiat, Tokyo 1600023, Japan

关键词: Corticosterone;    Depression;    Dopamine;    Exercise;    Medial prefrontal cortex;    Stress;   

DOI  :  10.1016/j.psyneuen.2016.03.008

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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