Behavioral effects of caffeine, (-)N-((R)-1-methyl-2-phenylethyl)-adenosine (PIA), and their combination in the mouse

The effects of caffeine (1–100 mg/kg, IP), (-)N-((R)-1-methyl-2-phenylethyl)-adenosine (PIA) (0.01–1 mg/kg, IP), and of the two drugs in combination were studied in mice responding under a mult FR30 FI600 s schedule of food presentation. The lowest dose of caffeine, 1 mg/kg, had no effect on responding under either component of the mult schedule. Intermediate doses of caffeine (3 and 10 mg/kg) slightly increased responding under the FI component, while higher doses decreased responding. Caffeine only decreased responding, at doses above 30 mg/kg, under the FR component. PIA decreased responding under both components of the mult schedule in a dose-dependent, and similar, manner. In most cases, the rate-increasing effect of caffeine on FI responding was diminished when combined with a rate-decreasing dose of PIA. However, when 0.01 mg/kg PIA, a dose that had no effect alone, was combined with 3 mg/kg caffeine, the increase in rate exceeded that of caffeine alone. Rate-deceasing effects of PIA were antagonized by caffeine; with larger doses of PIA, larger doses of caffeine were required for antagonism. Thus, while the rate-increasing effects of caffeine can be either enhanced or diminished, when combined with different doses of PIA, the rate-decreasing effects of PIA are clearly antagonized by caffeine in a dose-dependent manner.