Effects of Physical Exercise on Depression and Anxiety-Like Behaviors in Rodent Models of Maternal Separation: A Systematic Review and Meta-Analysis

Year 2025, Issue: Advanced Online Publication, 777 - 787

Yang Yang , Yuping Zhu , Bolin Chen , Yun Li , Hansen Li , Guodong Zhang

https://doi.org/10.56639/jsar.1720636

Abstract

Early-life maternal separation (MS) in rodents has been associated with long-term disruptions in psychological development, potentially increasing susceptibility to mood and anxiety disorders. Exercise has been proposed as a non-pharmacologic intervention capable of mitigating behavioral disturbances induced by early-life stress. However, the efficacy of exercise across various behavioral domains and experimental paradigms in MS models remains incompletely characterized.We performed a systematic review and meta-analysis of preclinical studies evaluating the effects of exercise on depression- and anxiety-like behaviors in rodent models of maternal separation. Behavioral assessments included the Forced Swim Test (FST) and Open Field Test (OFT) for depressive phenotypes, and the Elevated Plus Maze (EPM) for anxiety-related outcomes. Fourteen studies comprising 18 independent datasets met inclusion criteria. Of these, 11 reported FST outcomes, 3 reported OFT data, and 4 included EPM measures.Exercise significantly reduced immobility time in the FST among MS-exposed rodents (mean difference, −63.64 seconds; 95% CI, −84.21 to −43.06; P < 0.00001), indicating attenuation of depression-like behavior. In the OFT, exercise was associated with increased exploratory activity (mean difference, 44.32 units; 95% CI, 30.86 to 57.78; P < 0.00001). A nonsignificant trend toward reduced anxiety-like behavior was observed in the EPM (mean difference,26.23,95% CI, 16.14to36.32, P < 0.00001). Substantial heterogeneity was observed, likely reflecting variation in MS protocols and exercise regimens.In rodent models of maternal separation, physical exercise is associated with significant reductions in depression-like behavior and increased exploratory activity, with a potential—though inconclusive—benefit for anxiety-related outcomes. These findings support the therapeutic potential of exercise in mitigating the long-term behavioral sequelae of early-life stress.

Keywords

maternal separation , exercise , depression , anxiety

Project Number

NO

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