Antipsychotic Potential of Quinazoline ErbB1 Inhibitors in a Schizophrenia Model Established With Neonatal Hippocampal Lesioning
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- Mizuno Makoto
- Center for Transdisciplinary Research, Niigata University, Japan
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- Iwakura Yuriko
- Molecular Neurobiology, Brain Research Institute, Niigata University, Japan
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- Shibuya Masako
- Molecular Neurobiology, Brain Research Institute, Niigata University, Japan
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- Zheng Yingjun
- Molecular Neurobiology, Brain Research Institute, Niigata University, Japan
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- Eda Takeyoshi
- Molecular Neurobiology, Brain Research Institute, Niigata University, Japan
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- Kato Taisuke
- Molecular Neurobiology, Brain Research Institute, Niigata University, Japan
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- Takasu Yohei
- Molecular Neurobiology, Brain Research Institute, Niigata University, Japan
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- Nawa Hiroyuki
- Center for Transdisciplinary Research, Niigata University, Japan Molecular Neurobiology, Brain Research Institute, Niigata University, Japan
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Hyper-signaling of the epidermal growth factor receptor family (ErbB) is implicated in the pathophysiology of schizophrenia. Various quinazoline inhibitors targeting ErbB1 or ErbB2 – 4 have been developed as anti-cancer agents and might be useful for antipsychotic treatment. In the present study, we used an animal model of schizophrenia established by neonatal hippocampal lesioning and evaluated the neurobehavioral consequences of ErbB1-inhibitor treatment. Subchronic administration of the ErbB1 inhibitor ZD1839 to the cerebroventricle of rats receiving neonatal hippocampal lesioning ameliorated deficits in prepulse inhibition as well as those in the latent inhibition of tone-dependent fear learning. There were no apparent adverse effects on basal learning scores or locomotor activity, however. The administration of other ErbB1 inhibitors, PD153035 and OSI-774, similarly attenuated the prepulse inhibition impairment of this animal model. In parallel, there were decreases in ErbB1 phosphorylation in animals treated with ErbB1 inhibitors. These results indicate an antipsychotic potential of quinazoline ErbB1 inhibitors. ErbB receptor tyrosine kinases may be novel therapeutic targets for schizophrenia or its related psychotic symptoms.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 114 (3), 320-331, 2010
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390282680157356288
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- NII論文ID
- 10029890524
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- NII書誌ID
- AA11806667
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- COI
- 1:CAS:528:DC%2BC3cXhsFaqs7zI
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 10887938
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- PubMed
- 20962455
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可