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

• Published in: Psychopharmacology 2001-08, Vol.156 (4), p.461-468
• Main Authors: Paronis, C A, Cox, E D, Cook, J M, Bergman, J
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130100754

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. 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. 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. 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. 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.