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

Journal of Neural Transmission
Emma Perez-CostasRosalinda C Roberts

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 D(2) 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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Citations

Jun 17, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·John D ElsworthRobert H Roth
Jan 10, 2016·Neuropharmacology·Brian L TengSheryl S Moy
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