Discriminative stimulus properties of alprazolam.
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.
Gommans
J
J
Department of Psychopharmacology, Faculty of Pharmacy, Universiteit Utrecht, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.
Hijzen
T H
TH
Maes
R A
RA
Olivier
B
B
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
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