title: Involvement of the N-methyl-D-aspartate receptor GluN2D subunit in phencyclidine-induced motor impairment, gene expression, and increased Fos immunoreactivity.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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 administration in the basal ganglia motor circuit in WT mice but not GluN2D KO mice.
  
  
  CONCLUSIONS
  These results suggest that the GluN2D subunit within the motor circuitry is a key subunit for PCP-induced motor impairment, which requires an intricate balance between GluN2C- and GluN2D-mediated excitatory outputs.
authors: Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. yamamoto-hd@igakuken.or.jp.
authors: Hideko
authors: H
authors: Yamamoto
authors: Etsuko
authors: E
authors: Kamegaya
authors: Wakako
authors: W
authors: Sawada
authors: Ryota
authors: R
authors: Hasegawa
authors: Toshifumi
authors: T
authors: Yamamoto
authors: Yoko
authors: Y
authors: Hagino
authors: Yukio
authors: Y
authors: Takamatsu
authors: Kazuhide
authors: K
authors: Imai
authors: Hisashi
authors: H
authors: Koga
authors: Masayoshi
authors: M
authors: Mishina
authors: Kazutaka
authors: K
authors: Ikeda
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019295:Computational Biology; D003620:Dantrolene / Q000008:administration & dosage / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D010622:Phencyclidine / Q000633:toxicity*; D021122:Protein Subunits / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015203:Reproducibility of Results; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics
chemical_list: C464436:NR2D NMDA receptor; D021122:Protein Subunits; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D003620:Dantrolene; D010622:Phencyclidine