Different types of GABA(A) receptors may mediate the anticonflict and response rate-decreasing effects of zaleplon, zolpidem, and midazolam in squirrel monkeys

Psychopharmacology (Berl). 2001 Aug;156(4):461-8. doi: 10.1007/s002130100754.


Rationale: The role of different types of GABA(A) receptors in mediating anticonflict and response rate-decreasing effects of benzodiazepines in primate species is not known.

Objective: To examine the behavioral effects of the benzodiazepine-site, GABA(A) agonists zolpidem, zaleplon, and midazolam in the presence of two antagonists, flumazenil and beta-carboline-3-carboxylate-t-butyl ester (beta-CCt) in squirrel monkeys.

Methods: Two schedules of operant responding were used: (1) a multiple fixed-ratio (FR) schedule of food presentation involving punished and nonpunished behavior, and (2) an FR schedule of stimulus shock-termination.

Results: Midazolam (0.03-1.0 mg/kg), zolpidem (0.1-3.0 mg/kg), and zaleplon (0.1-3.0 mg/kg) increased rates of punished responding and decreased rates of nonpunished responding under the multiple schedule. Pretreatment with flumazenil (0.3-1.0 mg/kg) antagonized the anticonflict and response rate-decreasing effects of all three agonists. Pretreatment with beta-CCt (3-10 mg/kg) antagonized the anticonflict and rate-decreasing effects of midazolam, as well as the rate-decreasing effects of zolpidem and zaleplon. However, beta-CCt did not antagonize the anticonflict effects of zolpidem and zaleplon; instead, these effects of zolpidem and zaleplon were apparently enhanced in the presence of beta-CCt. Under the schedule of stimulus shock-termination, both flumazenil and beta-CCt antagonized zolpidem and zaleplon; however, the effects of beta-CCt were less consistent than the effects of flumazenil.

Conclusion: In nonhuman primates, different types of GABAA receptors may mediate the anticonflict and the response rate-decreasing effects of the nonselective GABAA agonist midazolam and the selective GABAA1 agonists zolpidem and zaleplon.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetamides / pharmacology*
  • Animals
  • Carbolines / pharmacology
  • Dose-Response Relationship, Drug
  • Flumazenil / pharmacology
  • GABA Antagonists / pharmacology
  • GABA Modulators / pharmacology
  • GABA-A Receptor Agonists
  • Hypnotics and Sedatives / pharmacology*
  • Male
  • Midazolam / pharmacology*
  • Pyridines / pharmacology*
  • Pyrimidines / pharmacology*
  • Reaction Time / drug effects*
  • Reaction Time / physiology
  • Receptors, GABA-A / physiology*
  • Saimiri
  • Zolpidem


  • Acetamides
  • Carbolines
  • GABA Antagonists
  • GABA Modulators
  • GABA-A Receptor Agonists
  • Hypnotics and Sedatives
  • Pyridines
  • Pyrimidines
  • Receptors, GABA-A
  • Flumazenil
  • Zolpidem
  • tert-butyl beta-carboline-3-carboxylate
  • Midazolam
  • zaleplon