Functional antagonism of the caffeine-discriminative stimulus by triazolam in humans

Six healthy male volunteers (aged 21-31 yr) were trained to discriminate between the methylxanthine caffeine (320 mg/70 kg, p.o.; e.g. drug A) and placebo (drug B). Then dose-effect curves were determined for triazolam (0.1-0.56 mg/70 kg), alone and in combination with the caffeine training dose (n = 6), buspirone (1.0-32.0 mg/70 kg), alone and in combination with the caffeine training dose (n = 4), and caffeine (56-560 mg/70 kg), alone and in combination with a selected dose of triazolam (n = 5). Triazolam blocked the discriminative effects of the caffeine training dose in a dose-related manner in five out of six subjects; whereas buspirone did so in only one out of four subjects. Different doses of caffeine alone generally produced dose-related increases in caffeine-appropriate responding; when administered concomitantly with triazolam, the caffeine dose-effect curve shifted significantly to the right. Triazolam and caffeine, but not buspirone and caffeine, generally produced significant interactions on several self-report and psychomotor performance measures. These results indicate that, at the doses tested, the caffeine discriminative stimulus can be blocked, at least partly by triazolam, but not by buspirone, which is consistent with the pharmacological actions of these compounds.