A Within-Subject Model of Hot Flash-Like Symptoms in Aged Rats
Abstract
Hot flashes are a common vasomotor symptom (VMS) experienced by postmenopausal women. In rodents, VMS-like symptoms can be assessed by monitoring tail skin temperature (TST), which reflects thermoregulatory changes. However, because the TST is highly sensitive to handling and environmental stresses, a reliable assessment requires continuous monitoring under low-stress and unrestrained conditions. In this study, we established a monitoring system for aged Wistar rats and evaluated hot flash-like symptoms using a within-subjects design across four physiological states: intact, ovariectomized (OVX), 17β-estradiol (E2) treatment, and E2 withdrawal. E2 treatment significantly decreased dark-phase TST (26.63 ± 0.26°C) compared with OVX (29.39 ± 0.18°C), and this effect was reversed upon pellet removal. We also quantified ΔTST, defined as the difference between light- and dark-phase TST, and found that E2 treatment markedly increased ΔTST, indicating an estrogen-dependent restoration of circadian TST amplitude. Because aged rats exhibit irregular estrous cycles and reduced ovarian steroidogenesis, yet remain underutilized in VMS research, this model provides a physiologically relevant platform for studying menopausal vasomotor dysfunction. By repeatedly monitoring the same individuals, inter-individual variability is minimized and reliable detection of within-subject changes is achieved with a small number of animals. These findings demonstrate that our method enables reliable long-term TST monitoring under unrestrained conditions and offers a practical and validated approach for investigating the pathophysiology of menopausal vasomotor dysfunction and for screening candidate compounds targeting hot flash-like symptoms in rodents.
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BibTeX
@article{okamoto2026withinsubject,
title = {{A Within-Subject Model of Hot Flash-Like Symptoms in Aged Rats}},
author = {Yoshinori Okamoto and Akira Aoki and Shinya Shibutani and Hideto Jinno},
journal = {Biological and Pharmaceutical Bulletin},
year = {2026},
month = jul,
doi = {10.1248/bpb.b25-00821},
url = {https://www.jstage.jst.go.jp/article/bpb/49/7/49_b25-00821/_article},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - A Within-Subject Model of Hot Flash-Like Symptoms in Aged Rats
AU - Yoshinori Okamoto
AU - Akira Aoki
AU - Shinya Shibutani
AU - Hideto Jinno
PY - 2026
DA - 2026/07/08
JO - Biological and Pharmaceutical Bulletin
DO - 10.1248/bpb.b25-00821
UR - https://www.jstage.jst.go.jp/article/bpb/49/7/49_b25-00821/_article
AB - Hot flashes are a common vasomotor symptom (VMS) experienced by postmenopausal women. In rodents, VMS-like symptoms can be assessed by monitoring tail skin temperature (TST), which reflects thermoregulatory changes. However, because the TST is highly sensitive to handling and environmental stresses, a reliable assessment requires continuous monitoring under low-stress and unrestrained conditions. In this study, we established a monitoring system for aged Wistar rats and evaluated hot flash-like symptoms using a within-subjects design across four physiological states: intact, ovariectomized (OVX), 17β-estradiol (E2) treatment, and E2 withdrawal. E2 treatment significantly decreased dark-phase TST (26.63 ± 0.26°C) compared with OVX (29.39 ± 0.18°C), and this effect was reversed upon pellet removal. We also quantified ΔTST, defined as the difference between light- and dark-phase TST, and found that E2 treatment markedly increased ΔTST, indicating an estrogen-dependent restoration of circadian TST amplitude. Because aged rats exhibit irregular estrous cycles and reduced ovarian steroidogenesis, yet remain underutilized in VMS research, this model provides a physiologically relevant platform for studying menopausal vasomotor dysfunction. By repeatedly monitoring the same individuals, inter-individual variability is minimized and reliable detection of within-subject changes is achieved with a small number of animals. These findings demonstrate that our method enables reliable long-term TST monitoring under unrestrained conditions and offers a practical and validated approach for investigating the pathophysiology of menopausal vasomotor dysfunction and for screening candidate compounds targeting hot flash-like symptoms in rodents.
SN - 1347-5215
SN - 0918-6158
ER -