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


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.

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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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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).

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