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.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd_retro-1069 |
| Date | 01 January 2007 |
| Creators | Wood, Erin |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Retrospective ETD Collection |
| Rights | © The Author |
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