title: Different types of GABA(A) receptors may mediate the anticonflict and response rate-decreasing effects of zaleplon, zolpidem, and midazolam in squirrel monkeys.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.affiliation: Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. cparonis@hms.harvard.edu
authors.forename: C A
authors.initials: CA
authors.lastname: Paronis
authors.forename: E D
authors.initials: ED
authors.lastname: Cox
authors.forename: J M
authors.initials: JM
authors.lastname: Cook
authors.forename: J
authors.initials: J
authors.lastname: Bergman
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology*; D012453:Saimiri; D000077334:Zolpidem
chemical_list: D000081:Acetamides; D002243:Carbolines; D018756:GABA Antagonists; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives; D011725:Pyridines; D011743:Pyrimidines; D011963:Receptors, GABA-A; D005442:Flumazenil; D000077334:Zolpidem; C043232:tert-butyl beta-carboline-3-carboxylate; D008874:Midazolam; C085665:zaleplon