The Journal of Physiological Sciences

, Volume 68, Issue 4, pp 425–430 | Cite as

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 ShimizuEmail author
Original Paper


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.


Adenosine Electrocardiogram Hibernation Hypothermia 


Author contributions

HS, TK and KM contributed to collection, analysis and interpretation of data and wrote the article. YSa, KN and HN performed acquisition of data. TS participated in the design of the study and helped to draft the manuscript. YSh was a supervisor in this study and revised the article critically for important intellectual content. All authors read and approved the final manuscript.

Compliance with ethical standards


This research was supported in part by Grants-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (15K14876 and 25660249).

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The experimental procedures were performed according to the guidelines for the care and use of laboratory animals approved by the Animal Care and Use Committee of Gifu University (permission numbers: 14102 and 15096). This article does not contain any studies with human participants performed by any of the authors.


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Copyright information

© The Physiological Society of Japan and Springer Japan 2017

Authors and Affiliations

  1. 1.Department of Basic Veterinary Science, Laboratory of Physiology, The United Graduate School of Veterinary SciencesGifu UniversityGifuJapan
  2. 2.Laboratory of Veterinary Physiology, Faculty of Applied Biological SciencesGifu UniversityGifuJapan
  3. 3.Center for Highly Advanced Integration of Nano and Life Sciences (G-CHAIN)Gifu UniversityGifuJapan

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