| Project/Area Number |
10670929
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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 | National Institute of Neuroscience, NCNP |
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Principal Investigator |
NISHIKAWA Toru Dep. Mental Disorder Res. Natl. Inst. Neurosci. Director, 神経研究所・疾病研究第三部, 部長 (00198441)
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| Co-Investigator(Kenkyū-buntansha) |
KAJII Yasuki Dep. Mental Disorder Res. Natl. Inst. Neurosci. Secnior Researcher, 神経研究所・疾病研究第三部, 研究員 (40291942)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Schizophrenia / Methamphetamine / Phencyclidine / Neocortex / Positive symptoms / Negative symptoms / RNA arbitrarily primed PCR / Postnatal development / Methanphetamine / differential cloning |
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| Research Abstract |
Schizophrenic symptoms occur after adolescence and the ability of psychotogenic drugs to induce schizophrenia-like psychosis is also age-dependent. Moreover, the behavioral responses to psychotogenic drugs in experimental animals apparently depend upon postnatal development. To obtain a clue for the molecular basis of neural dyfunction in schizophrenia, we have investigated the effects of different types of schizophrenomimetic drugs, methamphetamine (MAP) and phencyclidine (PCP) on gene expression in the brains of developing rats. Immunocytochemical analysis of expression of c-Fos gene product as a marker for the change in neuronal activity that the distribution patterns of MAP- and PCP-induced c-Fos protein-like immunoreactivity in the brain markedly changed in the neocortex or striatum, but not in the pyriform cortex, olfactory tubercle and septum, during postnatal development. The adult pattern was seen after 21 - 23 postnatal days. Since MAP-induced behavioral sensitization and an adult pattern of PCP-induced abnormal behavior has been observed to occur after the third week of postnatal life, these findings suggest that the maturation of certain neuronal circuits in the neocortex and/or striatum could, at least in part, be involved in the development of the behavioral responses to these drug. To further explore certain genes that play a crucial role in the maturation of these behavioral responses, we have studied differences in MAP- or PCP-induced gene expression in the discrete brain regions between neonatal and adult period using a RNA arbitrarily primed PCR technique.
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