Using thermal preference to understand mouse thermal biology

The ability to tightly regulate and maintain a warm core body temperature (T_b) is a defining characteristic of homeotherms. Moving to a thermally preferred place is an energetically efficient first-line thermoregulatory mechanism. We optimized a mouse binary thermal preference assay, selecting floor plate temperatures of 38°C versus 25°C for males and 39°C versus 30°C for females as having no baseline preference. Warm preference was increased in females, by fasting, and with age. Genetic manipulations that increased warm preference included ablation of uncoupling protein 1 (Ucp1) or of all four adenosine receptors (Adora1, Adora2a, Adora2b, Adora3). Ablation of estrogen receptor α (Esr1) reduced the preference for the warmer side in females but had no effect on preference in males. Mice treated with the β₃ adrenergic receptor agonist CL-316243 or the A3 adenosine receptor agonist MRS5698 sought the cooler surface. Thermal preference assays complement the measurement of T_b, providing information about whether a change in T_b reflects a new target or set point T_b caused by the intervention, or if the mouse is trying to maintain an unchanged T_b. Thermal preference can be more sensitive than baseline T_b for detecting changes in thermal physiology.NEW & NOTEWORTHY A thermal preference assay optimized for each sex demonstrated preference differences depending on physiologic state, genetic manipulation, and drug treatment. Thermal preference assays provide information that is complementary to measurement of core body temperature. Thermal preference can be more sensitive to perturbations than baseline body temperature and informs the understanding of how genetic, pharmacologic, and physiologic interventions alter thermoregulatory drive.