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Neuroleptics and animal models: feasibility of oral treatment monitored by plasma levels and receptor occupancy assays

Journal of Neural Transmission volume 115, pages 745–753 (2008)Cite this article

Abstract

The administration of neuroleptics in animal models has been extensively reported and plays an important role in the study of schizophrenia. Our study was designed to address the following questions: (1) Is it possible to achieve steady-state receptor occupancy levels administering neuroleptics in drinking water? (2) Is there an appropriate dose to obtain clinically comparable receptor occupancies? (3) Is there a correlation between plasma drug levels and receptor occupancy? Thus, we tested three neuroleptic drugs administered in drinking water for 7 days. Plasma drug levels were measured, and in vivo receptor occupancy assays were performed in order to determine peak and trough dopamine D2 receptor occupancies in striatal brain samples. Overall, our study indicates that in rodents the administration of appropriate doses of haloperidol and olanzapine in drinking water achieves receptor occupancies comparable to the clinical occupancy levels, but this appears not to be the case for clozapine.

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Acknowledgments

We wish to thank Elli Lilly and Co. (Indianapolis, IN, USA) for the donation of the olanzapine used in this study, and Novartis (Basel, Switzerland) for the donation of the clozapine. This work was supported by NIH grant MH66123.

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Affiliations

  1. Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, SPARKS Center (SC865), 1720 7th Avenue South, Birmingham, AL, 35294, USA

    Emma Perez-Costas, Miguel Melendez-Ferro & Rosalinda C. Roberts

  2. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, 21228, USA

    Paolo Guidetti & Joyce J. Kelley

Authors
  1. Emma Perez-Costas
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  2. Paolo Guidetti
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  3. Miguel Melendez-Ferro
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  4. Joyce J. Kelley
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  5. Rosalinda C. Roberts
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Correspondence to Emma Perez-Costas.

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Perez-Costas, E., Guidetti, P., Melendez-Ferro, M. et al. Neuroleptics and animal models: feasibility of oral treatment monitored by plasma levels and receptor occupancy assays. J Neural Transm 115, 745–753 (2008). https://doi.org/10.1007/s00702-007-0004-5

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  • DOI: https://doi.org/10.1007/s00702-007-0004-5

Keywords

  • Haloperidol
  • Clozapine
  • Olanzapine
  • Raclopride
  • Schizophrenia
  • Catalepsy
  • Drug efficacy
  • D2 receptor
  • Dopamine