2002 Fiscal Year Final Research Report Summary
Hippocampal knock down of NMDA receptor induces deficit of PPI
| Project/Area Number |
13671031
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Kitasato University |
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Principal Investigator |
SUZUKI Eiji Kitasato Univ. school of Medicine, Assistant Professor, 医学部, 専任講師 (60226496)
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| Co-Investigator(Kenkyū-buntansha) |
NIBUYA Masashi National Defense Medical College, Assistant Professor, 医学部, 講師 (00228256)
MIYAOKA Hitoshi Kitasato Univ. school of Medicine, Professor, 医学部, 教授 (40209862)
SAIJI Makoto Kitasato Univ. school of Allied Health Sciences, Professor, 医療衛生学部, 教授 (50114179)
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| Project Period (FY) |
2001 – 2002
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| Keywords | NMDA receptor / knock down / learning / nitric oxide / behavior / PPI |
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| Research Abstract |
The present experiment conformed to the Guidelines on the ethical use of laboratory animals of Kitasato University. Male Wistar rats were used. The NR1 hippocampal knockdown was performed by single injection of NR1 antisense-HVJ-liposome complex into the bilateral hippocampus of rats. The sustained downregulation of expression of NR1 by NR1-antisense was confirmed by western blot analysis. Western blot analysis demonstrated that the NR1-antisense treatment provided specifically the downregulation (about 30%) of NR1 expression in the hippocampus for more than a week. Firstly, it was shown that disruption of pre-pulse inhibition (PPI) was produced in the rats with antisense-induced hippocampal knockdown of NMDA receptor NR1 subunit (NR1). Next, we examined whether this disruption of PPI in NR1 knockdown rats was recovered by dopamine receptor antagonist haloperidol (HPD), to clarify the relation between glutamate dysfunction and dopamine hyperfunction. On the PPI test, application of moderate or high dose of HPD induced recovery from defective PPI in the rats with NR1 knockdown by antisense.
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