Induction of hibernation-like hypothermia by central activation of the A1 adenosine receptor in a non-hibernator, the rat

Hiroki Shimaoka, Takayuki Kawaguchi, Kahori Morikawa, Yuuki Sano, Kiyotada Naitou, Hiroyuki Nakamori, Takahiko Shiina, Yasutake Shimizu

Central adenosine A1-receptor (A1AR)-mediated signals play a role in the induction of hibernation. We determined whether activation of the central A1AR enables rats to maintain normal sinus rhythm even after their body temperature has decreased to less than 20 °C. Intracerebroventricular injection of an adenosine A1 agonist, N6-cyclohexyladenosine (CHA), followed by cooling decreased the body temperature of rats to less than 20 °C. Normal sinus rhythm was fundamentally maintained during the extreme hypothermia. In contrast, forced induction of hypothermia by cooling anesthetized rats caused cardiac arrest. Additional administration of pentobarbital to rats in which hypothermia was induced by CHA also caused cardiac arrest, suggesting that the operation of some beneficial mechanisms that are not activated under anesthesia may be essential to keep heart beat under the hypothermia. These results suggest that central A1AR-mediated signals in the absence of anesthetics would provide an appropriate condition for maintaining normal sinus rhythm during extreme hypothermia.