Treatment with an adenosine receptor antagonist completely blocks fasting‐induced torpor in mice

Abstract

When calorically restricted at cool ambient temperatures, mice conserve energy by entering torpor, during which core body temperature (Tb) and heart rate (HR) decrease. The application of exogenous adenosine produces hypothermia and bradycardia that mimic a torpid state. In this study, we used the non‐specific adenosine receptor antagonist aminophylline to test the hypothesis that adenosine signaling is necessary for the initiation of torpor in fasted mice. Male C57BL/6J mice were infused with aminophylline at a rate of 7 mg kg−1 hr−1 while Tb and HR were continuously monitored using implanted radiotelemeters. Over the course of a 23 hour fast at an ambient temperature of 20°C, all control mice exhibited torpor bouts, reaching a minimum Tb of 26.6 ± 1.1 °C with an average Tb of 32.6 ± 0.8 °C. However, aminophylline‐treated fasted mice did not enter torpor, with a minimum Tb of 34.4 ± 0.7 °C and an average Tb of 37.3 ± 0.2 °C. Likewise, the HR of control fasted mice fell to 153 ± 15 bpm, while aminophylline‐treated mice had a minimum HR of 359 ± 24 bpm over the fasted period. These findings support our hypothesis that adenosine receptor signaling is necessary for the induction of torpor in mice.