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 A(1) and A(2A) 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 A(1) receptor knockout mice, but not in A(2A) receptor knockout mice. Thus, caffeine-induced wakefulness depends on adenosine A(2A) receptors.