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Defense Date


Document Type


Degree Name

Master of Science



First Advisor

Dr. Joseph H. Porter


Ziprasidone (ZPD) is an atypical antipsychotic drug (APD) that has been shown to fully substitute in C57BL/6 mice for the discriminative stimulus properties of the atypical APD clozapine (CLZ). In rats, however, it has failed to substitute for either 1.25 mg/kg or 5.0 mg/kg training doses of CLZ. Here the discriminative stimulus properties of ZPD were examined by training 19 adult male Sprague-Dawley rats to discriminate 2.0 mg/kg ZPD from vehicle in a two-lever drug discrimination procedure (ED50 = 0.07 mg/kg). The atypical APD CLZ produced full substitution (ED50 =0.76 mg/kg), as did the atypical APDs zotepine (ED50 = 0.63 mg/kg), olanzapine (ED50 = 0.25 mg/kg), quetiapine (ED50 = 0.93 mg/kg), and risperidone (ED50 = 0.09 mg/kg). The 5-HT2A antagonist ritanserin also fully substituted for ZPD (ED50 = 1.27 mg/kg). Partial substitution (2A/B/C receptors play an important role in the discriminative stimulus properties of ZPD and perhaps the ratio of binding to 5-HT2A/B/C and D2 receptors. While it will be necessary to test additional APDs, these initial findings suggest that ZPD drug discrimination may be a useful model to differentiate atypical from typical APDs.


Part of Retrospective ETD Collection, restricted to VCU only.


© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

June 2008