Effects of long-term treatment with the neuroleptics haloperidol, clozapine and olanzapine on immunoexpression of NMDA receptor subunits NR1, NR2A and NR2B in the rat hippocampus

Krzystanek, Marek and Bogus, Katarzyna and Pałasz, Artur and Krzystanek, Ewa and Worthington, John J. and Wiaderkiewicz, Ryszard (2015) Effects of long-term treatment with the neuroleptics haloperidol, clozapine and olanzapine on immunoexpression of NMDA receptor subunits NR1, NR2A and NR2B in the rat hippocampus. Pharmacological reports : PR, 67 (5). pp. 965-969. ISSN 1734-1140

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Abstract

BACKGROUND: Antagonists of the N-methyl-d-aspartate receptor (NMDA-R) are associated with symptoms of schizophrenia, leading to the hypothesis that NMDA-R hypofunction leads to the pathogenesis of disease. We evaluated the long-term effect of neuroleptic administration on the NMDA subunits via immunohistochemical analysis. METHODS: Rats received olanzapine, clozapine and haloperidol before evaluation of the expression of the NR1, NR2A and NR2B subunit proteins in the hippocampal areas of the brain, via a densytometric analysis of immunoexpression in the rat hippocampus. RESULTS: All of the neuroleptics examined caused a decrease in the expression of the NR1 subunit, and thus, one can assume that both olanzapine, clozapine and haloperidol decreased the number of NMDA receptors in the CA1 and CA2 areas of the brain. CONCLUSIONS: A decrease in hippocampal glutamatergic signalling after long-term neuroleptic administration may cautiously explain the incomplete effectiveness of these drugs in the therapy of schizophrenia-related cognitive disturbances.

Item Type:
Journal Article
Journal or Publication Title:
Pharmacological reports : PR
Additional Information:
Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/3000/3004
Subjects:
ID Code:
78915
Deposited By:
Deposited On:
04 Apr 2016 12:18
Refereed?:
Yes
Published?:
Published
Last Modified:
07 Apr 2020 03:47