2024-03-29T00:35:16Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/664162022-11-17T02:08:08Zhdl_2115_20040hdl_2115_121The role of medial prefrontal corticosterone and dopamine in the antidepressant-like effect of exerciseChen, ChongNakagawa, ShinKitaichi, YujiAn, YanOmiya, YukiSong, NingKoga, MinoriKato, AkikoInoue, TakeshiKusumi, IchiroCorticosteroneDepressionDopamineExerciseMedial prefrontal cortexStress490Despite 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.ElsevierJournal Articleapplication/pdfapplication/pdfhttp://hdl.handle.net/2115/66416https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/66416/2/Psychoneuroendocrinology69_1-SD.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/66416/1/Psychoneuroendocrinology69_1.pdf0306-4530AA00792662Psychoneuroendocrinology69192016-07enginfo:pmid/27003115info:doi/10.1016/j.psyneuen.2016.03.008© 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/author