Dose-dependent surmountability of locomotor activity in caffeine tolerance.

For two chronic intraperitoneal caffeine dose regimens (10 and 80 mg/kg per day), tolerance developed rapidly (2-3 days) to the stimulatory effects of caffeine on locomotor activity. However, surmountability of the tolerant activity rate levels by caffeine administration was dose dependent: Activity rate was restored fully by acute caffeine administration for the 10 mg/kg per day series, but not for the 80 mg/kg per day series. The extent of tolerance was also dose-dependent: Tolerance was incomplete for the low-dose daily caffeine series but complete for the high-dose series. Upon discontinuation of daily caffeine dosing, activity rate decreased to the original baseline levels for both chronic series. Caffeine tolerance and the quantification of its surmountability may be explained by the pharmacokinetics of caffeine and the upregulation of adenosine receptors.