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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doaj-f1731dcf2aa04832b08497dabf8697062021-08-26T13:52:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-01228672867210.3390/ijms22168672NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in RatsAbdallah Ahnaou0Kobe Heleven1Ria Biermans2Nikolay V. Manyakov3Wilhelmus H. Drinkenburg4Department of Neuroscience, Data Science, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, BelgiumDepartment of Neuroscience, Data Science, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, BelgiumDepartment of Neuroscience, Data Science, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, BelgiumDepartment of Neuroscience, Data Science, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, BelgiumDepartment of Neuroscience, Data Science, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, BelgiumSynaptic 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.https://www.mdpi.com/1422-0067/22/16/8672synaptic plasticityhippocampusLTPNMDA receptorketamineNR2B |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Abdallah Ahnaou Kobe Heleven Ria Biermans Nikolay V. Manyakov Wilhelmus H. Drinkenburg |
spellingShingle |
Abdallah Ahnaou Kobe Heleven Ria Biermans Nikolay V. Manyakov Wilhelmus H. Drinkenburg NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in Rats International Journal of Molecular Sciences synaptic plasticity hippocampus LTP NMDA receptor ketamine NR2B |
author_facet |
Abdallah Ahnaou Kobe Heleven Ria Biermans Nikolay V. Manyakov Wilhelmus H. Drinkenburg |
author_sort |
Abdallah Ahnaou |
title |
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_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_sort |
nmdars containing nr2b subunit do not contribute to the ltp form of hippocampal plasticity: in vivo pharmacological evidence in rats |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-08-01 |
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. |
topic |
synaptic plasticity hippocampus LTP NMDA receptor ketamine NR2B |
url |
https://www.mdpi.com/1422-0067/22/16/8672 |
work_keys_str_mv |
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