Caffeine Has Similar Pharmacokinetics and Behavioral Effects via the IP and PO Routes of Administration

Abstract

Caffeine administered intraperitoneally (IP) or orally (PO) decreased the reinforcement rate and increased the nonreinforced response rate in a dose-related fashion under a differential reinforcement of low rate schedule (DRL 45-s) in 3-h sessions. These effects were similar following both routes of caffeine administration. The parallel pharmacokinetics for IP and PO caffeine were each determined and related to the respective effects of caffeine on reinforcement rate. Serum caffeine concentrations were similar across the session after the absorption phase for a given dose. Consequently, the effect remained in approximately the same range within a dose, and no single dose possessed a full concentration–effect relation for the two routes. The effects of IP and PO caffeine on reinforcement rate plateaued at doses higher than 40 mg/kg, which produced a serum caffeine concentration of approximately 25 μg/ml regardless of the route of administration. The EC 50 values were 7.34 and 9.93 μg/ml for IP and PO caffeine, respectively. This study as well as our previous studies demonstrated that the IP route is dependable for studying caffeine dose–response relations but not for studying other drugs (e.g., midazolam). The possible mechanism accounting for this difference is discussed.