title: Discriminative stimulus properties of alprazolam.
abstract: BACKGROUND
  The triazolobenzodiazepine alprazolam has a unique clinical profile compared to most other benzodiazepines (e.g. diazepam, chlordiazepoxide), in that it is used to treat panic disorder and is effective in depression, two disorders that are usually treated with anti-depressants. Previous drug discrimination studies suggested that alprazolam has stimulus properties in common with antidepressants.
  
  
  OBJECTIVE
  In the present study, the discriminative stimulus properties of alprazolam were investigated to test more conclusively the role of benzodiazepine receptors and whether alprazolam has stimulus properties in common with antidepressants.
  
  
  METHODS
  Male Wistar rats (n=12) were trained to discriminate between alprazolam (2.0 mg/kg, PO) and vehicle in an operant two-lever drug discrimination procedure under a tandem VI40"-FR10 schedule of reinforcement. Generalization and antagonism tests were carried out under 2 min extinction.
  
  
  RESULTS
  In generalization tests, a number of benzodiazepines (alprazolam, chlordiazepoxide, midazolam, lorazepam) and the barbiturate pentobarbital substituted completely, while zolpidem and abecarnil substituted partially for alprazolam. In contrast, no significant degree of generalization to the antidepressants imipramine and fluvoxamine and the putative antidepressants buspirone and flesinoxan was found. In antagonism studies alprazolam could be antagonized (almost) completely by flumazenil, partially by pentylenetetrazole, but not by methyl 6, 7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), N-methyl-beta-carboline-3-carboxamide (FG-7142) and picrotoxin.
  
  
  CONCLUSIONS
  These results show that the discriminative stimulus properties of alprazolam are mediated by benzodiazepine receptors and that the finding that antidepressants share discriminative stimulus effects with alprazolam may have limited generality.
authors.affiliation: Department of Psychopharmacology, Faculty of Pharmacy, Universiteit Utrecht, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Gommans
authors.forename: T H
authors.initials: TH
authors.lastname: Hijzen
authors.forename: R A
authors.initials: RA
authors.lastname: Maes
authors.forename: B
authors.initials: B
authors.lastname: Olivier
mesh_terms: D000525:Alprazolam / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003292:Convulsants / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D003292:Convulsants; D018682:GABA Agents; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D005442:Flumazenil; D016666:Fluvoxamine; D010433:Pentylenetetrazole; D000525:Alprazolam