title: Emergence of anti-conflict effects of zolpidem in rhesus monkeys following extended post-injection intervals.
abstract: BACKGROUND
  Zolpidem is a hypnotic drug that binds to γ-aminobutyric acid type A receptors but lacks consistently demonstrable anxiolytic efficacy.
  
  
  METHODS
  Rhesus monkeys (N = 4) were trained under a multiple schedule in which food-maintained responding was programmed (18-response fixed ratio) for a 5-min period, followed by a 5-min period in which the food-maintained responding was suppressed by response-contingent electric shock (20-response fixed ratio). Doses of zolpidem (range = 0.03 to 1.0 mg/kg, i.v.) were administered 5 min before the session, and responding was re-assessed at three additional 20-min intervals. A similar experiment also was carried out with the non-selective benzodiazepine, triazolam, over a dose range of 0.001 to 0.1 mg/kg, i.v.
  
  
  RESULTS
  Zolpidem did not engender a significant increase in average rates of suppressed responding at earlier time points; however, rates of non-suppressed responding were robustly decreased. At 45- and 65-min post-injection, zolpidem treatment resulted in a dose-dependent increase in rates of suppressed responding. In contrast, the non-selective benzodiazepine triazolam increased rates of suppressed responding in a dose-dependent manner at all four time points, although decreases in non-suppressed responding were less at the later time points.
  
  
  CONCLUSIONS
  These findings suggest that zolpidem has anxiolytic-like effects, but only >25 min after i.v. injection in this rhesus monkey conflict model. It was hypothesized that time-dependent effects on the response rate-suppressing properties of zolpidem become tolerant (i.e., acute tolerance). Because anxiolytic-like effects remain stable throughout the session, the absence of rate-decreasing effects may "unmask" anti-conflict effects.
authors.affiliation: New England Primate Research Center, Harvard Medical School, P.O. Box 9102, Pine Hill Drive, Southborough, MA 01772-9102, USA. james_rowlett@hms.harvard.edu
authors.forename: James K
authors.initials: JK
authors.lastname: Rowlett
authors.forename: John H
authors.initials: JH
authors.lastname: Kehne
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Sprenger
authors.forename: George D
authors.initials: GD
authors.lastname: Maynard
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003220:Conflict, Psychological; D004597:Electroshock; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D011485:Protein Binding; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000378:metabolism; D012054:Reinforcement, Psychology; D013997:Time Factors; D000077334:Zolpidem
chemical_list: D014151:Anti-Anxiety Agents; D011725:Pyridines; D011963:Receptors, GABA-A; D000077334:Zolpidem