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EXAMINATION OF THE DISCRIMINATIVE STIMULUS AND CROSS-TOLERANCE INDUCING PROPERTIES OF N-DESMETHYLCLOZAPINE IN C57BL/6 MICE.

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.

Identiferoai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-2748
Date24 April 2009
CreatorsWiebelhaus, Jason
PublisherVCU Scholars Compass
Source SetsVirginia Commonwealth University
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceTheses and Dissertations
Rights© The Author

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