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Vol. 280, Issue 1, 162-173, 1997
Department of Psychiatry and Human Behavior (J.K.R., W.L.W.) and
Department of Pharmacology and Toxicology (W.L.W.), University of
Mississippi Medical Center, Jackson, Mississippi
The present study compared the discriminative stimulus effects of the
imidazopyridine, zolpidem, with a triazolobenzodiazepine, triazolam, in
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 in pentobarbital-appropriate responding that
reached 80% or greater at the highest doses tested. Zolpidem, but not
triazolam, increased latency to respond in a dose-dependent manner.
Sprague-Dawley rats (n = 12), trained to discriminate pentobarbital (8.0 mg/kg i.p.) from saline under 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 
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 were maximal at the
5-min pretreatment time and had dissipated after the 45-min
pretreatment time. Further studies were conducted in rats to equate
procedural variables between the monkey and rat studies. When the FR
was reduced from 10 to 1, zolpidem occasioned 26 to 62%
pentobarbital-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 possibility of a species difference between nonhuman primates
and rats in the pentobarbital-like discriminative stimulus effects of
zolpidem.
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