Generalization Testing with Atypical and Typical Antipsychotic Drugs in Rats Trained to Discriminate 5.0 Mg/Kg Clozapine from Vehicle in a Two-Choice Drug Discrimination Task
Document Type
Article
Publication Date
1-1-2005
Abstract
Clozapine (CLZ) drug discrimination is used as a preclinical model to evaluate compounds for putative atypical antipsychotic properties. In rats, a 1.25 mg/kg CLZ training dose appears to have greater pharmacological specificity for atypical antipsychotic drugs than the traditional 5.0 mg/kg CLZ training dose; however, methodological differences among studies have precluded a direct comparison between these training doses. In the present study, rats were trained to discriminate a 5.0 mg/kg CLZ dose from vehicle in a two-choice drug discrimination task using methods similar to those in a previous study from our laboratory that used a 1.25 mg/kg CLZ training dose. Clozapine produced full substitution (≥80% CLZ-lever responding) for itself at the training dose (5.0 mg/kg). The atypical antipsychotics olanzapine, quetiapine, and ziprasidone also produced full substitution for 5.0 mg/kg CLZ, whereas the atypical antipsychotics risperidone and sertindole produced partial substitution (≥60% CLZ-lever responding). The typical antipsychotic, thioridazine, produced full substitution for the 5.0 mg/kg CLZ training dose, but the typical antipsychotics chlorpromazine, fluphenazine, and haloperidol failed to substitute for clozapine. In a subgroup of 1.25 mg/kg CLZ-trained rats, ziprasidone produced strong partial substitution (73.0% CLZ-lever responding) for the 1.25 mg/kg CLZ training dose. Based on these findings, some atypical antipsychotic drugs (i.e., quetiapine and ziprasidone) produce full substitution only for the 5.0 mg/kg CLZ training dose, whereas other atypical antipsychotic drugs (i.e., sertindole and risperidone) produce full substitution only for the 1.25 mg/kg CLZ training dose. Thus, both of these training doses are important for the screening of putative atypical antipsychotic drugs with the clozapine drug discrimination assay.
DOI
10.1002/ddr.10419
MSU Digital Commons Citation
Prus, Adam J.; Philibin, Scott D.; Pehrson, Alan; Stephens, Chad L.; Cooper, Rhiannon N.; Wise, Laura E.; and Porter, Joseph H., "Generalization Testing with Atypical and Typical Antipsychotic Drugs in Rats Trained to Discriminate 5.0 Mg/Kg Clozapine from Vehicle in a Two-Choice Drug Discrimination Task" (2005). Department of Psychology Faculty Scholarship and Creative Works. 241.
https://digitalcommons.montclair.edu/psychology-facpubs/241