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PMID: 18193153 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Journal of neural transmission (Vienna, Austria : 1996) ·Vol. 115 ·No. 5 ·2008-05-00 ·Pages 745-53

Perez-Costas E, Guidetti P, Melendez-Ferro M, Kelley JJ, Roberts RC

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.

MeSH Terms
Administration, Oral Analysis of Variance Animals Antipsychotic Agents/administration & dosage,blood Behavior, Animal/drug effects Benzodiazepines/administration & dosage Catalepsy/chemically induced Clozapine/administration & dosage Dose-Response Relationship, Drug Drinking/drug effects Haloperidol/administration & dosage Male Models, Animal Olanzapine Protein Binding/drug effects Rats Rats, Sprague-Dawley Receptors, Dopamine D2/drug effects,metabolism Time Factors
Chemicals
Antipsychotic Agents Receptors, Dopamine D2 Benzodiazepines Clozapine Haloperidol Olanzapine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Perez-Costas Emma
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, SPARKS Center (SC865), Birmingham, AL 35294, USA. [email protected]
Guidetti Paolo
Melendez-Ferro Miguel
Kelley Joyce J
Roberts Rosalinda C
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Article Info
Journal
Journal of neural transmission (Vienna, Austria : 1996)
Abbr.
J Neural Transm (Vienna)
ISSN
0300-9564
DOI
10.1007/s00702-007-0004-5
Email
[email protected]
Published
2008-05-00
Epub
2008-00-11
Pages
745-53
Language
English
Region
Austria
NLM ID
9702341
PMCID
PMC2410030
Subset
IM
Grants
NIMH NIH HHS · R01 MH066123-05 · United States
NIMH NIH HHS · R01 MH066123 · United States
NIMH NIH HHS · R01 MH066123-02 · United States
NIMH NIH HHS · R01 MH066123-03 · United States
NIMH NIH HHS · R01 MH066123-04 · United States
NIMH NIH HHS · R01 MH066123-01A1 · United States
NIMH NIH HHS · MH 66123 · United States
External Links
PubMed source DOI: 10.1007/s00702-007-0004-5 PMC Full Text View journal details
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