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

Abstract

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.

• Authors: C A Paronis, E D Cox, J M Cook, J Bergman
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 156 Issue 4 Pg. 461-8 (Aug 2001) ISSN: 0033-3158 [Print] Germany
• PMID: 11498724 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 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

Topics

• 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, physiology)
• Receptors, GABA-A (physiology)
• Saimiri
• Zolpidem