title: The role of medial prefrontal corticosterone and dopamine in the antidepressant-like effect of exercise.
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 (CORT), 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 CORT, 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.
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. Electronic address: snakaga@med.hokudai.ac.jp.
authors.forename: Shin
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kitaichi
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Omiya
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan; Department of Psychiatry, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Song
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Minori
authors.initials: M
authors.lastname: Koga
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kato
authors.affiliation: Department of Psychiatry, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kusumi
mesh_terms: D000818:Animals; D000928:Antidepressive Agents; D003345:Corticosterone / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000378:metabolism; D003866:Depressive Disorder / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010805:Physical Conditioning, Animal / Q000502:physiology / Q000523:psychology; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000928:Antidepressive Agents; D005938:Glucocorticoids; D006220:Haloperidol; D004298:Dopamine; D003345:Corticosterone
keywords: Corticosterone; Depression; Dopamine; Exercise; Medial prefrontal cortex; Stress