DISCRIMINATIVE STIMULUS EFFECTS OF ZOLPIDEM IN PENTOBARBITAL-TRAINED SUBJECTS .2. COMPARISON WITH TRIAZOLAM AND CAFFEINE IN HUMANS

In the present study, four non-drug-abusing humans were trained to dis criminate between a hypnotic dose of pentobarbital, 100 mg, and placeb o. After acquiring the pentobarbital-placebo discrimination, a range o f doses of zolpidem, triazolam, pentobarbital and caffeine were tested to determine whether they shared discriminative stimulus effects with the training dose of pentobarbital. Zolpidem, a rapid-onset, short-du ration, quickly eliminated imidazopyridine hypnotic agent, was tested because its discriminative stimulus effects have been shown to differ from those of classic sedative/hypnotic compounds in rodents, but not in nonhuman primates. Triazolm and caffeine were included as positive and negative controls, respectively. The subject-rated and performance -impairing effects of zolpidem, triazolam, pentobarbital and caffeine were assessed concurrently. These four subjects met the discrimination criterion (greater than or equal to 80% correct drug identifications on four consecutive sessions) in 4 to 18 (mean = 8.5) sessions, and th e pentobarbital-placebo discrimination was well maintained during a te st-of-novel-doses and test-of-novel-drugs phase (i.e., placebo and 100 mg pentobarbital occasioned 0-35% [mean = 17%] and 75-100% [mean = 85 %] drug-appropriate responding, respectively). Zolpidem, triazolam and pentobarbital generally produced dose-related increases in pentobarbi tal-appropriate responding and sedative-like, subject-rated drug effec ts. Caffeine on average produced low levels of pentobarbital-appropria te responding, although some doses of caffeine produced maximal pentob arbital-appropriate responding in some subjects. Caffeine produced som e stimulant-like (e.g., jittery, motivated, nervous and stimulated) su bject-rated drug effects. Zolpidem and triazolam, and to a much lesser extent pentobarbital, but not caffeine, impaired performance. These r esults suggest that humans can acquire and maintain a pentobarbital-pl acebo discrimination, and this discrimination is pharmacologically spe cific. These results also suggest that despite the somewhat unique bio chemical profile of zolpidem, its discriminative stimulus, subject-rat ed and performance-pairing effects are similar to those of classic sed ative/hypnotic compounds like the barbiturates and benzodiazepines. Fi nally, the results observed in the present study with zolpidem, triazo lam and caffeine demonstrate that the discriminative stimulus effects of drugs observed with nonhuman primates can be systematically replica ted in humans.