Clozapine discrimination with a low training dose distinguishes atypical from typical antipsychotic drugs in rats

Rationale: Previous drug discrimination studies with clozapine have not rel iably distinguished between atypical and typical antipsychotics. Objectives . The present study was conducted to determine whether low-dose clozapine d rug discrimination could distinguish atypical from typical antipsychotics. Methods: Rats were trained to discriminate 1.25 mg/kg clozapine from vehicl e in a two-lever drug discrimination procedure. Results: Generalization tes ting revealed full substitution with the atypical antipsychotics olanzapine (90.3% maximum generalization), sertindole (99.8%), and risperidone (87.1% ) and partial substitution for quetiapine (seroquel, 66.4%) and the typical antipsychotics haloperidol (56.8%) and thioridazine (74.3%). Remoxipride ( 23.1%) and the typical antipsychotics chlorpromazine (27.9%) and fluphenazi ne (29.5%) did not reliably substitute for clozapine. Conclusions: In contr ast to previous clozapine drug discrimination studies with higher training doses, the atypical antipsychotics olanzapine, sertindole, and risperidone reliably substituted for clozapine while typical antipsychotics did not. Th ese results suggest that low-dose clozapine drug discrimination may be a mo re sensitive assay for distinguishing atypical from typical antipsychotic d rugs.