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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Porkka-Heiskanen, T. et al. Science 276, 1265–1268 (1997).
Fredholm, B.B., Ijzerman, A.P., Jacobson, K.A., Klotz, K.N. & Linden, J. Pharmacol. Rev. 53, 527–552 (2001).
Basheer, R., Strecker, R.E., Thakkar, M.M. & McCarley, R.W. Prog. Neurobiol. 73, 379–396 (2004).
Hayaishi, O., Urade, Y., Eguchi, N. & Huang, Z.L. Arch. Ital. Biol. 142, 533–539 (2004).
Porkka-Heiskanen, T., Alanko, L., Kalinchuk, A. & Stenberg, D. Sleep Med. Rev. 6, 321–332 (2002).
Fredholm, B.B., Chen, J.F., Masino, S.A. & Vaugeois, J.M. Annu. Rev. Pharmacol. Toxicol. 45, 385–412 (2005).
Satoh, S., Matsumura, H., Suzuki, F. & Hayaishi, O. Proc. Natl. Acad. Sci. USA 93, 5980–5984 (1996).
Scammell, T.E. et al. Neuroscience 107, 653–663 (2001).
Hong, Z.Y. et al. J. Neurochem. 92, 1542–1549 (2005).
Fredholm, B.B., Battig, K., Holmen, J., Nehlig, A. & Zvartau, E.E. Pharmacol. Rev. 51, 83–133 (1999).
El Yacoubi, M., Ledent, C., Parmentier, M., Costentin, J. & Vaugeois, J.M. Neuropharmacology 45, 977–985 (2003).
Fisone, G., Borgkvist, A. & Usiello, A. Cell. Mol. Life Sci. 61, 857–872 (2004).
Rainnie, D.G., Grunze, H.C., McCarley, R.W. & Greene, R.W. Science 263, 689–692 (1994).
Mignot, E., Taheri, S. & Nishino, S. Nat. Neurosci. 5 (suppl.), 1071–1075 (2002).
Stenberg, D. et al. J. Sleep Res. 12, 283–290 (2003).
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.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn1491
- Springer Nature America, Inc.
This article is cited by
-
Parasubthalamic calretinin neurons modulate wakefulness associated with exploration in male mice
Nature Communications (2023)
-
Sleep Deprivation, Burnout, and Acute Care Surgery
Current Trauma Reports (2023)
-
The effect of preoperative aminophylline on the recovery profile after major pelvic-abdominal surgeries: a randomized controlled double-blinded study
BMC Anesthesiology (2021)
-
Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice
Nature Communications (2021)
-
Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway
Molecular Psychiatry (2021)