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Psychopharmacology

, Volume 165, Issue 3, pp 209–215 | Cite as

Discriminative stimulus effects of zolpidem in squirrel monkeys: role of GABAA1 receptors

  • James K. Rowlett
  • Roger D. Spealman
  • Snjezana Lelas
  • James M. Cook
  • Wenyuan Yin
Original Investigation

Abstract

Rationale. The discriminative stimulus effects of zolpidem in squirrel monkeys trained at doses greater than or equal to 3.0 mg/kg differ from those of conventional benzodiazepines (BZs), but the extent to which these effects reflect the selectivity of zolpidem for GABAA1 receptors is not known.

Objectives. The present study investigated the ability of GABAA1-preferring agonists to substitute for training doses of zolpidem greater than or equal to 3.0 mg/kg and the ability of GABAA1-preferring antagonists to block zolpidem's discriminative stimulus effects.

Methods. Squirrel monkeys were trained to discriminate intravenous injections of zolpidem (3.0 or 5.6 mg/kg) from saline and tested with BZ agonists differing in selectivity and efficacy at GABAA1 receptors. Antagonism of the effects of zolpidem was studied using the GABAA1-preferring antagonists β-carboline-3-carboxylate-t-butyl ester (β-CCT) and 3-propyloxy-β-carboline (3-PBC).

Results. Zolpidem and quazepam (GABAA1-preferring agonist) engendered full substitution for zolpidem, whereas CL 218,872 (GABAA1-preferring partial agonist) and the non-selective BZ agonists alprazolam and flunitrazepam engendered low and variable levels of zolpidem-lever responding (35–58%). Both β-CCT and 3-PBC antagonized the discriminative stimulus effects of zolpidem in a surmountable fashion.

Conclusions. Our findings provide evidence for a key role of GABAA1 receptors in the discriminative stimulus effects of zolpidem at relatively high training doses, and suggest that selectivity and relatively high efficacy at GABAA1 receptors is required for BZ agonists to reproduce these discriminative stimulus effects.

Zolpidem Benzodiazepine GABAA receptor subtype Discriminative stimulus Squirrel monkey 

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • James K. Rowlett
    • 1
  • Roger D. Spealman
    • 1
  • Snjezana Lelas
    • 1
  • James M. Cook
    • 2
  • Wenyuan Yin
    • 2
  1. 1.Harvard Medical School, New England Regional Primate Research Center, One Pine Hill Drive, Box 9102, Southborough, MA 01772-9102, USA
  2. 2.Department of Chemistry, University of Wisconsin – Milwaukee, Milwaukee, Wis., USA

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