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.