Limb restraint induces a rapid and profound decrease in core body temperature associated with the stress response in mice.

Stress responses are triggered by diverse stressors and typically involve acute common physiological changes including increased heart rate and adrenocortical hormone secretion. In contrast, core body temperature (Tc) may either increase or decrease depending on the stressor. Although restraint is widely used to induce stress responses in laboratory animals, heterogeneous effects on Tc have been reported. To elucidate the central and peripheral mechanisms underlying restraint-induced hypothermia, a reliable model that consistently induces hypothermia is first required. In this study, we aimed to establish an experimental system using mice that can reliably induce hypothermia through physical restraint. Furthermore, we aimed to elucidate the primary factors contributing to hypothermia within the various elements constituting the restrained state and to simplify the restraint experimental system by eliminating unnecessary elements. Starting with conventional cylinder-shaped restraint equipment and modifying it in various ways, we finally found that the simple procedure of limb restraint reliably induces a rapid (within 15 min) and substantial (∼4 °C) decrease in rectal temperature, a good indicator of Tc. Limb restraint increased serum corticosterone concentration and activated the paraventricular hypothalamic nucleus, suggesting that a type of stress response involving Tc reduction was induced by limb restraint. The decrease in body temperature caused by limb restraint was attributed, at least in part, to reduced heat production in the brown adipose tissue and increased heat loss from the tail. This simplified restraint paradigm provides a useful tool for elucidating the mechanisms underlying hypothermia induced by physical restraint.