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Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine

Nature Neuroscience volume 8, pages 858–859 (2005)Cite this article

Abstract

Caffeine, a component of tea, coffee and cola, induces wakefulness. It binds to adenosine A1 and A2A receptors as an antagonist, but the receptor subtype mediating caffeine-induced wakefulness remains unclear. Here we report that caffeine at 5, 10 and 15 mg kg−1 increased wakefulness in both wild-type mice and A1 receptor knockout mice, but not in A2A receptor knockout mice. Thus, caffeine-induced wakefulness depends on adenosine A2A receptors.

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Figure 1: Time course of changes in wakefulness after caffeine (15 mg kg−1) treatment.
Figure 2: Total time of wakefulness for 3 h after caffeine injection.

References

  1. Porkka-Heiskanen, T. et al. Science 276, 1265–1268 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fredholm, B.B., Ijzerman, A.P., Jacobson, K.A., Klotz, K.N. & Linden, J. Pharmacol. Rev. 53, 527–552 (2001).

    CAS  PubMed  Google Scholar 

  3. Basheer, R., Strecker, R.E., Thakkar, M.M. & McCarley, R.W. Prog. Neurobiol. 73, 379–396 (2004).

    Article  CAS  PubMed  Google Scholar 

  4. Hayaishi, O., Urade, Y., Eguchi, N. & Huang, Z.L. Arch. Ital. Biol. 142, 533–539 (2004).

    CAS  PubMed  Google Scholar 

  5. Porkka-Heiskanen, T., Alanko, L., Kalinchuk, A. & Stenberg, D. Sleep Med. Rev. 6, 321–332 (2002).

    Article  PubMed  Google Scholar 

  6. Fredholm, B.B., Chen, J.F., Masino, S.A. & Vaugeois, J.M. Annu. Rev. Pharmacol. Toxicol. 45, 385–412 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Satoh, S., Matsumura, H., Suzuki, F. & Hayaishi, O. Proc. Natl. Acad. Sci. USA 93, 5980–5984 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Scammell, T.E. et al. Neuroscience 107, 653–663 (2001).

    Article  CAS  PubMed  Google Scholar 

  9. Hong, Z.Y. et al. J. Neurochem. 92, 1542–1549 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Fredholm, B.B., Battig, K., Holmen, J., Nehlig, A. & Zvartau, E.E. Pharmacol. Rev. 51, 83–133 (1999).

    CAS  PubMed  Google Scholar 

  11. El Yacoubi, M., Ledent, C., Parmentier, M., Costentin, J. & Vaugeois, J.M. Neuropharmacology 45, 977–985 (2003).

    Article  CAS  PubMed  Google Scholar 

  12. Fisone, G., Borgkvist, A. & Usiello, A. Cell. Mol. Life Sci. 61, 857–872 (2004).

    Article  CAS  PubMed  Google Scholar 

  13. Rainnie, D.G., Grunze, H.C., McCarley, R.W. & Greene, R.W. Science 263, 689–692 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mignot, E., Taheri, S. & Nishino, S. Nat. Neurosci. 5 (suppl.), 1071–1075 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Stenberg, D. et al. J. Sleep Res. 12, 283–290 (2003).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported in part by grants-in-aid for scientific research from the Japan Society for the Promotion of Science (O.H., Z.-L.H.), the Program for Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN; Y.U.), Takeda Pharmaceutical Company Limited (O.H.) and Osaka City. This manuscript is dedicated to the late S. Fink to acknowledge his many scientific contributions to adenosine studies.

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Authors and Affiliations

  1. Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka, 565-0874, Japan

    Zhi-Li Huang, Wei-Min Qu, Naomi Eguchi, Yoshihiro Urade & Osamu Hayaishi

  2. Department of Neurology, Boston University School of Medicine, Boston, 02118, Massachusetts, USA

    Jiang-Fan Chen

  3. Molecular Neurobiology Laboratory, Massachusetts General Hospital, Boston, 02129, Massachusetts, USA

    Michael A Schwarzschild

  4. Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, S-17177, Sweden

    Bertil B Fredholm

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  1. Zhi-Li Huang
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Correspondence to Osamu Hayaishi.

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Huang, ZL., Qu, WM., Eguchi, N. et al. Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci 8, 858–859 (2005). https://doi.org/10.1038/nn1491

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