Discriminative stimulus effects of zolpidem in pentobarbital-trained subjects: I. Comparison with triazolam in rhesus monkeys and rats.
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 = 48%) at the 5- and 15-min pretreatment times and no drug-appropriate responding at the 45-min pretreatment time. In contrast, triazolam occasioned > or = 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 non-human primates and rats in the pentobarbital-like discriminative stimulus effects of zolpidem.
Rowlett
J K
JK
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, USA.
Woolverton
W L
WL
D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014229:Triazolam / Q000494:pharmacology*; D000077334:Zolpidem
D006993:Hypnotics and Sedatives; D011725:Pyridines; D014229:Triazolam; D000077334:Zolpidem; D010424:Pentobarbital