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

Rationale: The role of different types of GABAA receptors in mediating anti conflict and response rate-decreasing effects of benzodiazepines in primate species is not known. Objective: To examine the behavioral effects of the benzodiazepine-site, GABAA agonists zolpidem, zaleplon, and midazolam in th e presence of two antagonists, flumazenil and beta -carboline-3-carboxylate -t-butyl ester (beta -CCt) in squirrel monkeys. Methods: Two schedules of o perant responding were used: (1) a multiple fixed-ratio (FR) schedule of fo od 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 th e multiple schedule. Pretreatment with flumazenil (0.3-1.0 mg/kg) antagoniz ed the anticonflict and response rate-decreasing effects of all three agoni sts. Pretreatment with beta -CCt (3-10 mg/kg) antagonized the anticonflict and rate-decreasing effects of midazolam, as well as the rate-decreasing ef fects of zolpidem and zaleplon. However, beta -CCt did not antagonize the a nticonflict effects of zolpidem and zaleplon; instead, these effects of zol pidem and zaleplon were apparently enhanced in the presence of beta -CCt. U nder the schedule of stimulus shock-termination, both flumazenil and beta - CCt antagonized zolpidem and zaleplon; however, the effects of beta -CCt we re less consistent than the effects of flumazenil. Conclusion: In nonhuman primates, different types of GABAA receptors may mediate the anticonflict a nd the response rate-decreasing effects of the nonselective GABAA agonist m idazolam and the selective GABA(A1) agonists zolpidem and zaleplon.