Involvement of the N-methyl-D-aspartate receptor GluN2D subunit in phencyclidine-induced motor impairment, gene expression, and increased Fos immunoreactivity

Molecular Brain
Hideko YamamotoKazutaka Ikeda

Abstract

Noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists evoke a behavioral and neurobiological syndrome in experimental animals. We previously reported that phencyclidine (PCP), an NMDA receptor antagonist, increased locomotor activity in wildtype (WT) mice but not GluN2D subunit knockout mice. Thus, the aim of the present study was to determine whether the GluN2D subunit is involved in PCP-induced motor impairment. PCP or UBP141 (a GluN2D antagonist) induced potent motor impairment in WT mice but not GluN2D KO mice. By contrast, CIQ, a GluN2C/2D potentiator, induced severe motor impairment in GluN2D KO mice but not WT mice, suggesting that the GluN2D subunit plays an essential role in the effects of PCP and UBP141, and an appropriate balance between GluN2C and GluN2D subunits might be needed for appropriate motor performance. The level of the GluN2D subunit in the mature mouse brain is very low and restricted. GluN2D subunits exist in brainstem structures, the globus pallidus, thalamus, and subthalamic nucleus. We found that the expression of the c-fos gene increased the most among PCP-dependent differentially expressed genes between WT and GluN2D KO mice, and the number of Fos-positive cells increased after PCP admini...Continue Reading

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Citations

Jun 16, 2015·British Journal of Pharmacology·D Lodge, M S Mercier
May 29, 2019·The International Journal of Neuropsychopharmacology·Soichiro IdeKazutaka Ikeda
Jun 1, 2017·NPJ Schizophrenia·Kazu NakazawaKazuhito Nakao
Jun 11, 2021·Frontiers in Synaptic Neuroscience·Christophe J Dubois, Siqiong June Liu
Nov 25, 2021·Journal of Chemical Information and Modeling·Zhaoxi SunZhirong Liu

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