DISCRIMINATIVE STIMULUS EFFECTS OF ZOLPIDEM IN PENTOBARBIBTAL-TRAINEDSUBJECTS .1. COMPARISON WITH TRIAZOLAM IN RHESUS-MONKEYS AND RATS

The present study compared the discriminative stimulus effects of the imidazopyridine, zolpidem, with a triazolobenzodiazepine, triazolam, i n pentobarbital-trained rhesus monkeys and rats. Rhesus monkeys (n = 4 ), trained to discriminate pentobarbital (10 mg/kg intragastric [i.g.] ) from saline under a FR 1 discrete-trials shock avoidance procedure, were given zolpidem (0.10-30 mg/kg i.g.) or triazolam (0.01-0.3 mg/kg i.g.). Both zolpidem and triazolam produced dose-dependent increases i n pentobarbital-appropriate responding that reached 80% or greater at the higher doses tested. Zolpidem, but not triazolam, increased latenc y to respond in a dose-dependent manner. Sprague-Dawley rats (n = 12), trained to discriminate pentobarbital (8.0 mg/kg i.p.) from saline un der a FR 10 schedule of food reinforcement, were given zolpidem (0.50- 4.0 mg/kg i.p.; 5-, 15- and 45-min pretreatment) or triazolam (0.025-0 .20 mg/kg i.p., 15-min pretreatment). Zolpidem occasioned intermediate drug-appropriate responding (maximum group mean = 46%) at the 5- and 15-min pretreatment times and no drug-appropriate responding at the 45 -min pretreatment time. In contrast, triazolam occasioned greater than or equal to 80% pentobarbital-appropriate responding at 0.10 and 0.20 mg/kg. Both zolpidem and triazolam produced dose-dependent decreases in the rate of responding. The rate-decreasing effects of zolpidem wer e maximal at the 5-min pretreatment time and had dissipated after the 45-min pretreatment time. Further studies were conducted in rats to eq uate procedural variables between the monkey and rat. studies. When th e FR was reduced from 10 to 1, zolpidem occasioned 26 to 62% pentobarb ital-appropriate responding over a dose range of 1.0 to 6.0 mg/kg i.p. After i.g. administration, zolpidem occasioned 100% drug-appropriate responding at the highest dose tested; (6.0 mg/kg); however, only two of seven rats responded. Taken together, these data raise the possibil ity of a species difference between nonhuman primates and rats in the pentobarbital-like discriminative stimulus effects of zolpidem.