Brief Communication abstract

Nature Neuroscience 8, 858 - 859 (2005)
Published online: 19 June 2005 | doi:10.1038/nn1491

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

Zhi-Li Huang1, Wei-Min Qu1, Naomi Eguchi1, Jiang-Fan Chen2, Michael A Schwarzschild3, Bertil B Fredholm4, Yoshihiro Urade1 & Osamu Hayaishi1


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.

  1. Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan.
  2. Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
  3. Molecular Neurobiology Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02129, USA.
  4. Department of Physiology and Pharmacology, Karolinska Institute, S-17177 Stockholm, Sweden.

Correspondence to: Osamu Hayaishi1 e-mail:


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