Discriminative stimulus control with olanzapine: generalization to the atypical antipsychotic clozapine.
The present study was conducted to determine if the putative atypical antipsychotic olanzapine could be established as a discriminative stimulus in rats. Seven rats were successfully trained to discriminate olanzapine (0.5 mg/kg, IP) from vehicle in a two-lever drug discrimination procedure (mean number of acquisition sessions = 39.3). Generalization testing with olanzapine (0.0625-2.0 mg/kg) yielded an ED50 of 0.170 mg/kg (95% confidence interval = 0.118-0.246 mg/kg). The atypical antipsychotic clozapine (0.156-10.0 mg/kg) fully substituted for olanzapine in all rats at the 2.5 mg/kg dose with 99.0% drug-lever responding, in six rats at the 0.625 mg/kg dose, and in five rats at the 1.25 and 5.0 mg/kg doses (ED50 = 0.259 mg/kg, 95% confidence interval = 0.089-0.755 mg/kg). This study is the first demonstration that rats can be trained to discriminate olanzapine from vehicle in a two-lever drug discrimination procedure and that the olanzapine discrimination cue generalizes to clozapine.
Porter
J H
JH
Department of Psychology, Virginia Commonwealth University, Richmond 23284-2018, USA.
Strong
S E
SE
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines; D003024:Clozapine / Q000494:pharmacology*; D003216:Conditioning, Operant; D004305:Dose-Response Relationship, Drug; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D003024:Clozapine; D000077152:Olanzapine