Due to its unique receptor binding profile and its relationship to clozapine, N-desmethylclozapine (NDMC) has been examined as a possible antipsychotic drug (APD). Clozapine has been trained as discriminative stimulus in our lab, but NDMC has not yet been established as a discriminative stimulus. In experiment 1, 12 C57BL/6 mice were trained to discriminate 10.0 mg/kg NDMC from VEH using a standard-two lever operant procedure to assess antipsychotic substitution. The typical APD clozapine fully substituted for NDMC at 2 doses tested (2.5 and 5.0 mg/kg), while typical APD haloperidol failed to substitute for NDMC. In Experiment 2, 11 mice were given repeated administration of NDMC to assess cross-tolerance development to the discriminative stimulus of clozapine. NDMC was successfully trained as a discriminative stimulus and was also shown to induce cross-tolerance to clozapine’s discriminative stimulus, indicating similar underlying pharmacological mechanisms of action between NDMC and clozapine.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-2748 |
| Date | 24 April 2009 |
| Creators | Wiebelhaus, Jason |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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