Estrogen-mediated individual differences in female rat voluntary running behavior

Victoria Mathis, Lauren Points, Brock Pope, Chia-Ming Jimmy Lee, Merna Mohamed, Justin S. Rhodes, Peter Clark, Sarah Clayton, Li-Lian Yuan

Research output: Contribution to journalArticlepeer-review


Regular exercise has numerous health benefits, but the human population displays significant variability in exercise participation. Rodent models, such as voluntary wheel running (VWR) in rats, can provide insight into the underlying mechanisms of exercise behavior and its regulation. In this study, we focused on the role of estrogen on VWR in female rats. Female rats run more than males, and we aimed to determine to what extent running levels in females were regulated by estrogen signaling. The running behavior of rats (duration, speed, and total distance run) was measured under normal physiological conditions, ovariectomy (OVX), and estrogen replacement in an OVX background. Results show cyclic variations in running linked to the estrous cycle. Ovariectomy markedly reduced running and eliminated the cyclic pattern. Estrogen replacement through estradiol benzoate (EB) injections and osmotic minipumps reinstated running activity to pre-OVX levels and restored the cyclic pattern. Importantly, individual differences and ranking are preserved such that high versus low runners before OVX remain high and low runners after treatment. Further analysis revealed that individual variation in running distance was primarily caused by rats running different speeds, but rats also varied in running duration. However, it is noteworthy that this model also displays features distinct from estrogen-driven running behavior under physiological conditions, notably a delayed onset and a broader duration of running activity. Collectively, this estrogen causality VWR model presents a unique opportunity to investigate sex-specific mechanisms that control voluntary physical activity. NEW & NOTEWORTHY This study investigates estrogen’s role in voluntary wheel running (VWR) behavior in female rats. Female rats exhibit greater running than males, with estrogen signaling regulating this activity. The estrous cycle influences running, whereas ovariectomy reduces it, and estrogen replacement restores it, maintaining individual differences under all conditions. Both running speed and duration contribute to VWR variations. These findings emphasize individual estrogen regulation in female exercise and provide an estrogen replacement animal model for investigating neurobiological underpinnings that drive voluntary exercise behavior.

Original languageEnglish (US)
Pages (from-to)592-605
Number of pages14
JournalJournal of Applied Physiology
Issue number3
Early online dateFeb 1 2024
StatePublished - Mar 1 2024


  • Wheel running
  • estrogen receptor
  • estrogen replacement
  • ovariectomy
  • exercise motivation
  • wheel running

ASJC Scopus subject areas

  • General Medicine


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