| Project/Area Number |
08671124
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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 Instutitute of Neuroscience, NCNP |
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Principal Investigator |
NISHIKAWA Toru Dept.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) |
TAKAHASHI Katunobu Dept.Mental Disorder Res.Natl.Inst.Neurosci.Setion Chief, 神経センター・神経研究所・疾病研究第三部, 室長 (40183850)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Shizophrenia / Mammalian brains / NMDA receptor / Reverse tolerance / Tissue plasminogen acivator / Cerebral cortex / RNA arbitrarily primed PCR / Postnatal developemnt / Methanphetamine / アンチセンス法 / RNA arbitrarily primed PCR / methamphetamine / cocaine / 精神分裂病 / tissue plasminogen activator mRNA / in situ hybridization / 前頭葉皮質 / 梨状葉皮質 |
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| Research Abstract |
Stimulant-induced behavioral sensitization (reverse tolerance) has been considered to be an experimental model of susceptibility to recurrence of schizophrenia Acute injection of sensitization-inducing agents including methamphetamine (MAP), cocaine, nomifensine caused a transient and dose-dependent induction of tissue plasminogen activator (TPA) mRNA in the dorsomedial and insular prefrontal cortex and the piriformcortex of the rat. MAP-induction of TPA mRNA was markedly inhibited by D1 and D2 dopamine antagonists which have been shown to antagonize the ability of psychostimulants to develop behavioral sensitization. Moreover, intra-medial striatum, but not intra-lateral striatum and intra-thalamic, application of a fluorescent tracer, fluorogold, retrogradely labeled the cortical cells expressing TPA mRNA.These results suggest that a subpopulation of cortico-striatal pathways could be implicated in the development of behavioral sensitization and/or the pathophysiology of a group of shizophrenia. In the rat cortex, we have found the developmental changes in the distribution patterns of a neuronal activity marker, c-Fos, induced by phencyclidine (PCP) that causes schizophrenia-like positive and negative symptoms. These changes might reflect the maturation process of a subset of the cortical networks which could be disturbed in PCP psychosis and/or a subgroup of shizophrenia. To further explore the candidate genes related to schizophrenic symptoms, we have tried to find novel genes that specifically response to MAP or PCP by using RNA arbitrarily primed PCR.
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