Different baseline physical activity predicts susceptibility and resilience to chronic social defeat stress in mice: Involvement of dopamine neurons

•Mice could be segregated into high baseline physical activity (HBPA) and low baseline physical activity (LBPA) by voluntary wheel running (VWR).•LBPA mice had high susceptibility to chronic social defeat stress.•LBPA mice had low tyrosine hydroxylase (TH) levels in the ventral tegmental area.•Activ...

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Published in:European neuropsychopharmacology 2021-04, Vol.45, p.15-28
Main Authors: Zhang, Jing, He, Zhi-xiong, Qu, Yi-shan, Li, Lai-fu, Wang, Li-min, Yuan, Wei, Hou, Wen-juan, Zhu, Ying-qi, Cai, Wen-qi, Zhang, Xue-ni, Guo, Qian-qian, An, Shu-Cheng, Jia, Rui, Tai, Fa-dao
Format: Article
Language:English
Subjects:
Animals
Chronic social defeat stress
Dopaminergic Neurons
High baseline physical activity
Low baseline physical activity
Mice
Mice, Inbred C57BL
Motor Activity
Social Defeat
Stress, Psychological
Tyrosine 3-Monooxygenase
Tyrosine hydroxylase
Ventral Tegmental Area
Voluntary wheel running
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Summary:•Mice could be segregated into high baseline physical activity (HBPA) and low baseline physical activity (LBPA) by voluntary wheel running (VWR).•LBPA mice had high susceptibility to chronic social defeat stress.•LBPA mice had low tyrosine hydroxylase (TH) levels in the ventral tegmental area.•Activation of TH neurons of LBPA mice with DREADDs method increased VWR.•Activation of TH neurons of LBPA mice with DREADDs method decreased susceptibility to stress. Physical inactivity, the fourth leading mortality risk factor worldwide, is associated with chronic mental illness. Identifying the mechanisms underlying different levels of baseline physical activity and the effects of these levels on the susceptibility to stress is very important. However, whether different levels of baseline physical activity influence the susceptibility and resilience to chronic social defeat stress (CSDS), and the underlying mechanisms in the brain remain unclear. The present study segregated wild-type mice into low baseline physical activity (LBPA) and high baseline physical activity (HBPA) groups based on short term voluntary wheel running (VWR). LBPA mice showed obvious susceptibility to CSDS, while HBPA mice were resilient to CSDS. In addition, the expression of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) was lower in LBPA mice than in HBPA mice. Furthermore, activation of TH neurons in the VTA of LBPA mice by chemogenetic methods increased the levels of VWR and resilience to CSDS. In contrast, inhibiting TH neurons in the VTA of HBPA mice lowered the levels of VWR and increased their susceptibility to CSDS. Thus, this study suggests that different baseline physical activities might be mediated by the dopamine system. This system also affects the susceptibility and resilience to CSDS, possibly via alteration of the baseline physical activity. This perspective on the neural control and impacts on VWR may aid the development of strategies to motivate and sustain voluntary physical activity. Furthermore, this can maximize the impacts of regular physical activity toward stress-reduction and health promotion.
ISSN:0924-977X
1873-7862
DOI:10.1016/j.euroneuro.2021.02.011