Mice enter bouts of daily torpor, drastically reducing metabolic rate, core body temperature (T b), and heart rate (HR), in response to reduced caloric intake. Because central
adenosine activation has been shown to induce a torpor-like state in the arctic ground squirrel, and blocking the adenosine-1 (A1) receptor prevents daily torpor, we hypothesized that central activation of the A1
adenosine receptors would induce a bout of natural torpor in mice. To test the hypothesis, mice were subjected to four different
hypothermia bouts: natural torpor, forced
hypothermia (FH),
isoflurane-
anesthesia, and an intracerebroventricular injection of the selective A1 receptor agonist
N6-cyclohexyladenosine (CHA). All conditions induced profound
hypothermia. T b fell more rapidly in the FH,
isoflurane-
anesthesia, and CHA conditions compared to torpor, while mice treated with CHA recovered at half the rate of torpid mice. FH,
isoflurane-
anesthesia, and CHA-treated mice exhibited a diminished drop in HR during entry into
hypothermia as compared to torpor. Mice in all conditions except CHA shivered while recovering from
hypothermia, and only FH mice shivered substantially while entering
hypothermia. Circulating
lactate during the hypothermic bouts was not significantly different between the CHA and torpor conditions, both of which had lower than baseline
lactate levels. Arrhythmias were largely absent in the FH and
isoflurane-
anesthesia conditions, while skipped beats were observed in natural torpor and periodic extended (>1 s) HR pauses in the CHA condition. Lastly, the hypothermic bouts showed distinct patterns of gene expression, with torpor characterized by elevated hepatic and cardiac Txnip expression and all other hypothermic states characterized by elevated c-Fos and Egr-1 expression. We conclude that CHA-
induced hypothermia and natural torpor are largely different physiological states.