PT  - JOURNAL ARTICLE
AU  - James K. Rowlett
AU  - Roger D. Spealman
AU  - Snjezana Lelas
TI  - Discriminative Stimulus Effects of Zolpidem in Squirrel Monkeys: Comparison with Conventional Benzodiazepines and Sedative-Hypnotics
DP  - 1999 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1233--1241
VI  - 291
IP  - 3
4099  - http://jpet.aspetjournals.org/content/291/3/1233.short
4100  - http://jpet.aspetjournals.org/content/291/3/1233.full
SO  - J Pharmacol Exp Ther1999 Dec 01; 291
AB  - The present study examined whether zolpidem, an imidazopyridine with selectivity for benzodiazepine (BZ)/γ-aminobutyric acidAreceptors containing the α1-subunit, had discriminative stimulus effects similar to typical BZs and other sedative/hypnotic drugs in primates. Squirrel monkeys (Saimiri sciureus) were trained to discriminate zolpidem (1.0 mg/kg i.v.) from vehicle under a 10-response fixed-ratio schedule of food delivery. Under test conditions, zolpidem (0.1–3.0 mg/kg) increased responding on the drug lever to an average maximum of 90% of total responding. When pretreatment times were varied from 5 to 50 min, the discriminative stimulus effects of zolpidem were maximal at 5 min and near control levels 35 min after administration. Flumazenil antagonized both the discriminative stimulus and rate-decreasing effects of zolpidem in a dose-dependent and surmountable fashion (in vivo apparent pA2 values of 7.3 and 6.6 for the discriminative stimulus and rate-suppressing effects, respectively). The BZs triazolam, midazolam, diazepam, and N-desmethyldiazepam engendered dose-related increases in drug-lever responding that reached zolpidem-like levels (90%) in the majority of monkeys tested. In contrast, lorazepam, chlordiazepoxide, and oxazepam engendered average maximums of 70% or less and substituted fully for zolpidem in one or two monkeys only. Representative barbiturates as well as drugs that bind to non-BZ sites (muscimol, baclofen, buspirone, cyproheptadine, diphenhydramine) engendered 0 to 45% of responses on the drug lever up to doses that markedly reduced response rate. These results support the view that zolpidem's selectivity for the α1-subunit of the BZ/γ-aminobutyric acidA receptor complex confers a distinctive profile of interoceptive effects that overlaps partially with those of typical BZs but not with those of barbiturates. The American Society for Pharmacology and Experimental Therapeutics