Extended neuroleptic administration modulates NMDA-R subunit immunoexpression in the rat neocortex and diencephalon

Krzystanek, Marek and Bogus, Katarzyna and Palasz, Artur and Wiaderkiewicz, Anna and Filipczyk, Lukasz and Rojczyk, Ewa and Worthington, John Joseph and Wiaderkiewicz, Ryszard (2016) Extended neuroleptic administration modulates NMDA-R subunit immunoexpression in the rat neocortex and diencephalon. Pharmacological reports : PR, 68 (5). pp. 990-995. ISSN 1734-1140

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Background This study aimed to evaluate the effect of extended olanzapine, clozapine and haloperidol administration on NMDA-R subunit immunoexpression in the rat neocortex and diencephalon. Methods To explore NR1, NR2A and NR2B subunit protein expression, densytometric analysis of immunohistochemically stained brain slices was performed. Results Interestingly, 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. Conclusions Neuroleptic-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.

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Journal Article
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Pharmacological reports : PR
Additional Information:
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
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Deposited On:
02 Aug 2016 13:56
Last Modified:
15 Sep 2023 00:27