Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - 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
AU - Krzystanek, Marek
AU - Bogus, Katarzyna
AU - Pałasz, Artur
AU - Krzystanek, Ewa
AU - Worthington, John J.
AU - Wiaderkiewicz, Ryszard
N1 - Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
PY - 2015/10
Y1 - 2015/10
N2 - 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.
AB - 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.
U2 - 10.1016/j.pharep.2015.01.017
DO - 10.1016/j.pharep.2015.01.017
M3 - Journal article
C2 - 26398392
VL - 67
SP - 965
EP - 969
JO - Pharmacological reports : PR
JF - Pharmacological reports : PR
SN - 1734-1140
IS - 5
ER -