Rights statement: This is the author’s version of a work that was accepted for publication in Pharmacological Reports. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Pharmacological Reports, 68, 5, 2016 DOI: 10.1016/j.pharep.2016.05.009
Accepted author manuscript, 264 KB, PDF document
Available under license: CC BY-NC-ND: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Extended neuroleptic administration modulates NMDA-R subunit immunoexpression in the rat neocortex and diencephalon
AU - Krzystanek, Marek
AU - Bogus, Katarzyna
AU - Palasz, Artur
AU - Wiaderkiewicz, Anna
AU - Filipczyk, Lukasz
AU - Rojczyk, Ewa
AU - Worthington, John Joseph
AU - Wiaderkiewicz, Ryszard
N1 - This is the author’s version of a work that was accepted for publication in Pharmacological Reports. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Pharmacological Reports, 68, 5, 2016 DOI: 10.1016/j.pharep.2016.05.009
PY - 2016/10
Y1 - 2016/10
N2 - BackgroundThis study aimed to evaluate the effect of extended olanzapine, clozapine and haloperidol administration on NMDA-R subunit immunoexpression in the rat neocortex and diencephalon.MethodsTo explore NR1, NR2A and NR2B subunit protein expression, densytometric analysis of immunohistochemically stained brain slices was performed.ResultsInterestingly, all neuroleptics caused a downregulation of NMDA-R subunit expression in the thalamus but increased the level of NR1 in the hypothalamus. Olanzapine upregulated hypothalamic NR2A expression, while clozapine and haloperidol decreased hypothalamic levels. We observed no significant changes in NR2B immunoreactivity. None of the studied medications had significant influence on NMDA-R subunit expression in the neocortex.ConclusionsNeuroleptic-induced reduction in the expression of thalamic NMDA-R subunits may play an important role in the regulation of glutamatergic transmission disorders in cortico–striato–thalamo–cortical loop in schizophrenia. A decrease in NMDA signaling in this region after long-term neuroleptic administration may also cautiously explain the incomplete effectiveness of these drugs in the therapy of schizophrenia-related cognitive disturbances.
AB - BackgroundThis study aimed to evaluate the effect of extended olanzapine, clozapine and haloperidol administration on NMDA-R subunit immunoexpression in the rat neocortex and diencephalon.MethodsTo explore NR1, NR2A and NR2B subunit protein expression, densytometric analysis of immunohistochemically stained brain slices was performed.ResultsInterestingly, all neuroleptics caused a downregulation of NMDA-R subunit expression in the thalamus but increased the level of NR1 in the hypothalamus. Olanzapine upregulated hypothalamic NR2A expression, while clozapine and haloperidol decreased hypothalamic levels. We observed no significant changes in NR2B immunoreactivity. None of the studied medications had significant influence on NMDA-R subunit expression in the neocortex.ConclusionsNeuroleptic-induced reduction in the expression of thalamic NMDA-R subunits may play an important role in the regulation of glutamatergic transmission disorders in cortico–striato–thalamo–cortical loop in schizophrenia. A decrease in NMDA signaling in this region after long-term neuroleptic administration may also cautiously explain the incomplete effectiveness of these drugs in the therapy of schizophrenia-related cognitive disturbances.
KW - NMDA receptor
KW - neuroleptics
KW - glutamate
KW - neocortex
KW - diencephalon
U2 - 10.1016/j.pharep.2016.05.009
DO - 10.1016/j.pharep.2016.05.009
M3 - Journal article
VL - 68
SP - 990
EP - 995
JO - Pharmacological reports : PR
JF - Pharmacological reports : PR
SN - 1734-1140
IS - 5
ER -