Adenosine, AMP, and Daily Torpor

  • Steven J. Swoap
  • Benjamin Iliff
  • Son Le


When calorically restricted at cool ambient temperatures, mice conserve energy by entering torpor, during which metabolic rate (MR), core body temperature (T b), heart rate (HR), and locomotor activity (LMA) decrease. Others have suggested that injection of adenosine monophosphate (AMP) mimics the torpor pathway. We have postulated that AMP is dephosphorylated to adenosine which drastically slows HR, and the reduced oxygen delivery forces metabolism to fall with an accompanying decrease in T b. We would also predict an increase in anaerobic metabolism as oxygen delivery becomes limiting. To test this hypothesis, we measured circulating lactate, a marker for anaerobic metabolism, in C57Bl/6 mice, 30 min after treatment with AMP, ADP, adenosine, methacholine, and during fasting-induced torpor. HR slowed drastically with the treatments, from >600 bpm to <200 bpm within 1 min. Lactate levels rose from control values of 1.8 mm to >5 mm when treated with AMP or ADP, while lactate levels dropped during natural torpor (0.8 mm). Further, we show that adenosine signaling is necessary for the initiation and maintenance of torpor in fasted mice. Mice were subcutaneously (s.c.) infused with either saline or aminophylline, an adenosine receptor blocker, during fasting. Over the course of a 23 h fast, aminophylline significantly blunted the length of time in torpor fivefold. Also, when aminophylline was infused once torpor had begun, it reversed the hypometabolism, hypothermia, bradycardia, and hypoactivity of torpor, while saline did not. Finally, intracerebroventricular infusion of a polar adenosine receptor antagonist, which does not cross the blood–brain barrier, during fasting-induced torpor also induced emergence from torpor. These findings support the hypothesis that adenosine is necessary for the induction and maintenance of torpor in mice.


Blood Lactate Adenosine Receptor Dark Phase Torpor Bout Adenosine Receptor Antagonist 
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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of BiologyWilliams CollegeWilliamstownUSA

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