Swoap SJ, Rathvon M, Gutilla M. AMP does not induce torpor. Am J Physiol Regul Integr Comp Physiol 293: R468-R473, 2007. First published April 4, 2007; doi:10.1152/ajpregu.00888.2006.-Torpor, a state characterized by a well-orchestrated reduction of metabolic rate and body temperature (Tb), is employed for energetic savings by organisms throughout the animal kingdom. The nucleotide AMP has recently been purported to be a primary regulator of torpor in mice, as circulating AMP is elevated in the fasted state, and administration of AMP causes severe hypothermia. However, we have found that the characteristics and parameters of the hypothermia induced by AMP were dissimilar to those of fasting-induced torpor bouts in mice. Although administration of AMP induced hypothermia (minimum Tb ϭ 25.2 Ϯ 0.6°C) similar to the depth of fasting-induced torpor (24.9 Ϯ 1.5°C), ADP and ATP were equally effective in lowering T b (minimum Tb: 24.8 Ϯ 0.9°C and 24.0 Ϯ 0.5°C, respectively). The maximum rate of T b fall into hypothermia was significantly faster with injection of adenine nucleotides (AMP: Ϫ0.24 Ϯ 0.03; ADP: Ϫ0.24 Ϯ 0.02; ATP: Ϫ0.25 Ϯ 0.03°C/min) than during fasting-induced torpor (Ϫ0.13 Ϯ 0.02°C/min). Heart rate decreased from 755 Ϯ 15 to 268 Ϯ 17 beats per minute (bpm) within 1 min of AMP administration, unlike that observed during torpor (from 646 Ϯ 21 to 294 Ϯ 19 bpm over 35 min). Finally, the hypothermic effect of AMP was blunted with preadministration of an adenosine receptor blocker, suggesting that AMP action on T b is mediated via the adenosine receptor. These data suggest that injection of adenine nucleotides into mice induces a reversible hypothermic state that is unrelated to fasting-induced torpor. core body temperature; adenosine; hibernation; heart rate IN THE FACE OF COOL AMBIENT temperature (T a ) and diminished caloric availability, small mammals like mice can depress metabolic rate for enormous energetic savings. During the state of torpor, core T b in mice can be as deep as 20°C and can last from as little as a few minutes up to ϳ14 h (15, 17). Consistent with the fact that torpor in mice is dependent upon the lack of caloric availability, circulating hormones generated in the periphery that relay messages of both feeding status and fat availability play a critical role in determining 1) whether a mouse enters torpor and 2) the depth and duration of that torpor bout. For example, administration of ghrelin, a stomachderived hormone that is normally released during fasting periods (2, 40), deepens the torpor bout via neuropeptide Y neurons within the arcuate nucleus of the hypothalamus (18). Leptin, a fat-derived hormone, cues a response opposite of ghrelin. Administration of leptin prevents deep bouts of fasting-induced torpor (13,14,16). Mice missing leptin (i.e., ob/ob mice) undergo unusually long bouts of torpor (21, 36) and can enter torpor even in the fed state (41). We have recently shown that sympathetically mediated depression of circulating leptin during fasting is a requisite for initiation of...