Animal model of schizophrenia: Dysfunction of NMDA receptor-signaling in mice following withdrawal from repeated administration of phencyclidine

Toshitaka Nabeshima, Akihiro Mouri, Rina Murai, Yukihiro Noda

研究成果: Conference contribution

55 引用 (Scopus)

抄録

In humans, phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate(NMDA) antagonist, reproduces a schizophrenia-like psychosis such as positive/negative symptoms and cognitive deficits. PCP (10 mg/kg/day for 14 days)-treated mice exhibit the enhanced immobility in a forced swimming test as indexes of negative symptoms and impairment of latent learning in a water finding test as indexes of cognitive deficits. These behavioral deficits remain after withdrawal from repeated PCP treatment and are attenuated by atypical antipsychotics, but not by typical antipsychotics. Since it has been hypothesized that insufficient glutamate neurotransmission is involved in the pathophysiology of schizophrenia, we investigated an involvement of glutamatergic system in emotional and cognitive deficits in mice treated with PCP repeatedly. Ca2+/ calmodulin kinase II (CaMKII) is markedly phosphorylated after the forced swimming test and the training trial of water finding test in the prefrontal cortex of saline-treated mice but not PCP-treated mice. Facilitation of NMDA receptor function by NMDA receptor glycine-site agonists such as D-cycloserine and glycine is effective on the abnormal intracellular signaling, and emotional and cognitive deficits in mice treated with PCP repeatedly. The repeated PCP treatment impaired NMDA receptor function and decreased levels of spontaneous extracellular glutamate in the prefrontal cortex, indicating that the repeated PCP treatment impairs both pre- and postsynaptic glutamate transmissions. Our findings suggest that abnormal NMDA receptor signaling is involved in the emotional and cognitive deficits in mice treated with PCP repeatedly. Our PCP-treated mice would be a useful model for studying the effect of antipsychotics on emotional and cognitive deficits in schizophrenia.

元の言語English
ホスト出版物のタイトルIntegrated Molecular Medicine for Neuronal and Neoplastic Disorders
出版者Blackwell Publishing Inc.
ページ160-168
ページ数9
ISBN(印刷物)1573316555, 9781573316552
DOI
出版物ステータスPublished - 01-01-2006
外部発表Yes

出版物シリーズ

名前Annals of the New York Academy of Sciences
1086
ISSN(印刷物)0077-8923
ISSN(電子版)1749-6632

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Phencyclidine
N-Methyl-D-Aspartate Receptors
Schizophrenia
Animals
Animal Models
Antipsychotic Agents
Glutamic Acid
Glycine
Cycloserine
Calcium-Calmodulin-Dependent Protein Kinases
Water
Prefrontal Cortex
N-Methylaspartate
Neurobehavioral Manifestations
Animal Model
Mouse
Synaptic Transmission
Psychotic Disorders
Learning
Emotion

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

これを引用

Nabeshima, T., Mouri, A., Murai, R., & Noda, Y. (2006). Animal model of schizophrenia: Dysfunction of NMDA receptor-signaling in mice following withdrawal from repeated administration of phencyclidine. : Integrated Molecular Medicine for Neuronal and Neoplastic Disorders (pp. 160-168). (Annals of the New York Academy of Sciences; 巻数 1086). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1377.003
Nabeshima, Toshitaka ; Mouri, Akihiro ; Murai, Rina ; Noda, Yukihiro. / Animal model of schizophrenia : Dysfunction of NMDA receptor-signaling in mice following withdrawal from repeated administration of phencyclidine. Integrated Molecular Medicine for Neuronal and Neoplastic Disorders. Blackwell Publishing Inc., 2006. pp. 160-168 (Annals of the New York Academy of Sciences).
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Nabeshima, T, Mouri, A, Murai, R & Noda, Y 2006, Animal model of schizophrenia: Dysfunction of NMDA receptor-signaling in mice following withdrawal from repeated administration of phencyclidine. : Integrated Molecular Medicine for Neuronal and Neoplastic Disorders. Annals of the New York Academy of Sciences, 巻. 1086, Blackwell Publishing Inc., pp. 160-168. https://doi.org/10.1196/annals.1377.003

Animal model of schizophrenia : Dysfunction of NMDA receptor-signaling in mice following withdrawal from repeated administration of phencyclidine. / Nabeshima, Toshitaka; Mouri, Akihiro; Murai, Rina; Noda, Yukihiro.

Integrated Molecular Medicine for Neuronal and Neoplastic Disorders. Blackwell Publishing Inc., 2006. p. 160-168 (Annals of the New York Academy of Sciences; 巻 1086).

研究成果: Conference contribution

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Nabeshima T, Mouri A, Murai R, Noda Y. Animal model of schizophrenia: Dysfunction of NMDA receptor-signaling in mice following withdrawal from repeated administration of phencyclidine. : Integrated Molecular Medicine for Neuronal and Neoplastic Disorders. Blackwell Publishing Inc. 2006. p. 160-168. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1377.003