Aspirin-caffeine interaction in the rat.

Both aspirin at a high dose (400 mg kg-1) and caffeine (5 mg kg-1) induced hyperactivity in the DA rat, but lower doses of aspirin were without effect. Caffeine-induced hyperactivity was brief (2 h) but that due to aspirin was evident from 1--6 h after dosing. Co-administration of the two drugs caused long-lasting hyperactivity, even with doses of aspirin which had no stimulant effects themselves. Absorptive and metabolic effects did not appear to play a major role in the interaction. The most likely effect is that of salicylate on catecholamine utilization in the central nervous system, which is compounded in the presence of a phosphodiesterase inhibitor.