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NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in Rats

Synaptic plasticity is the key to synaptic health, and aberrant synaptic plasticity, which in turn impairs the functioning of large-scale brain networks, has been associated with neurodegenerative and psychiatric disorders. The best known and most studied form of activity-dependent synaptic plastici...

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Autores principales: Ahnaou, Abdallah, Heleven, Kobe, Biermans, Ria, Manyakov, Nikolay V., Drinkenburg, Wilhelmus H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395520/
https://www.ncbi.nlm.nih.gov/pubmed/34445376
http://dx.doi.org/10.3390/ijms22168672
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author Ahnaou, Abdallah
Heleven, Kobe
Biermans, Ria
Manyakov, Nikolay V.
Drinkenburg, Wilhelmus H.
author_facet Ahnaou, Abdallah
Heleven, Kobe
Biermans, Ria
Manyakov, Nikolay V.
Drinkenburg, Wilhelmus H.
author_sort Ahnaou, Abdallah
collection PubMed
description Synaptic plasticity is the key to synaptic health, and aberrant synaptic plasticity, which in turn impairs the functioning of large-scale brain networks, has been associated with neurodegenerative and psychiatric disorders. The best known and most studied form of activity-dependent synaptic plasticity remains long-term potentiation (LTP), which is controlled by glutamatergic N-methyl-d-aspartate) receptors (NMDAR) and considered to be a mechanism crucial for cellular learning and memory. Over the past two decades, discrepancies have arisen in the literature regarding the contribution of NMDAR subunit assemblies in the direction of NMDAR-dependent synaptic plasticity. Here, the nonspecific NMDAR antagonist ketamine (5 and 10 mg/kg), and the selective NR2B antagonists CP-101606 and Ro 25-6981 (6 and 10 mg/kg), were administered intraperitoneally in Sprague Dawley rats to disentangle the contribution of NR2B subunit in the LTP induced at the Schaffer Collateral-CA1 synapse using the theta burst stimulation protocol (TBS). Ketamine reduced, while CP-101606 and Ro 25-6981 did not alter the LTP response. The administration of CP-101606 before TBS did not influence the effects of ketamine when administered half an hour after tetanization, suggesting a limited contribution of the NR2B subunit in the action of ketamine. This work confirms the role of NMDAR in the LTP form of synaptic plasticity, whereas specific blockade of the NR2B subunit was not sufficient to modify hippocampal LTP. Pharmacokinetics at the doses used may have contributed to the lack of effects with specific antagonists. The findings refute the role of the NR2B subunit in the plasticity mechanism of ketamine in the model.
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spelling pubmed-83955202021-08-28 NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in Rats Ahnaou, Abdallah Heleven, Kobe Biermans, Ria Manyakov, Nikolay V. Drinkenburg, Wilhelmus H. Int J Mol Sci Article Synaptic plasticity is the key to synaptic health, and aberrant synaptic plasticity, which in turn impairs the functioning of large-scale brain networks, has been associated with neurodegenerative and psychiatric disorders. The best known and most studied form of activity-dependent synaptic plasticity remains long-term potentiation (LTP), which is controlled by glutamatergic N-methyl-d-aspartate) receptors (NMDAR) and considered to be a mechanism crucial for cellular learning and memory. Over the past two decades, discrepancies have arisen in the literature regarding the contribution of NMDAR subunit assemblies in the direction of NMDAR-dependent synaptic plasticity. Here, the nonspecific NMDAR antagonist ketamine (5 and 10 mg/kg), and the selective NR2B antagonists CP-101606 and Ro 25-6981 (6 and 10 mg/kg), were administered intraperitoneally in Sprague Dawley rats to disentangle the contribution of NR2B subunit in the LTP induced at the Schaffer Collateral-CA1 synapse using the theta burst stimulation protocol (TBS). Ketamine reduced, while CP-101606 and Ro 25-6981 did not alter the LTP response. The administration of CP-101606 before TBS did not influence the effects of ketamine when administered half an hour after tetanization, suggesting a limited contribution of the NR2B subunit in the action of ketamine. This work confirms the role of NMDAR in the LTP form of synaptic plasticity, whereas specific blockade of the NR2B subunit was not sufficient to modify hippocampal LTP. Pharmacokinetics at the doses used may have contributed to the lack of effects with specific antagonists. The findings refute the role of the NR2B subunit in the plasticity mechanism of ketamine in the model. MDPI 2021-08-12 /pmc/articles/PMC8395520/ /pubmed/34445376 http://dx.doi.org/10.3390/ijms22168672 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ahnaou, Abdallah
Heleven, Kobe
Biermans, Ria
Manyakov, Nikolay V.
Drinkenburg, Wilhelmus H.
NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in Rats
title NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in Rats
title_full NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in Rats
title_fullStr NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in Rats
title_full_unstemmed NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in Rats
title_short NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in Rats
title_sort nmdars containing nr2b subunit do not contribute to the ltp form of hippocampal plasticity: in vivo pharmacological evidence in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395520/
https://www.ncbi.nlm.nih.gov/pubmed/34445376
http://dx.doi.org/10.3390/ijms22168672
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