A comparison of the effects of caffeine, 8-cyclopentyltheophylline, and alloxazine on sleep in rats. Possible roles of central nervous system adenosine receptors.

The dose-response effects of administration of 8-cyclopentyltheophylline (CPT) (10, 20, and 40 mg/kg intraperitoneally [IP]) and alloxazine (ALX) (12.5, 25, and 50 mg/kg, IP) on sleep and wakefulness in rats were examined and compared to those of caffeine (12.5 mg/kg IP). Both CPT and ALX injected individually produced sleep suppression qualitatively similar to that produced by caffeine, but of a lower magnitude. However, when 20 mg/kg CPT and 50 mg/kg ALX were injected together, their sleep suppressant effect was of the same magnitude as that of 12.5 mg/kg caffeine. These results support the hypothesized involvement of adenosine receptor blockade in the effects of caffeine on sleep in rats. They further suggest that A1 adenosine receptor blockade may be more important than A2 receptor blockade, since behavioral effects of the selective in vitro A1 antagonist CPT were generally similar to those of nonselective in vitro adenosine receptor antagonists caffeine and ALX.