| Project/Area Number |
13671010
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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 | University of Tokushima |
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Principal Investigator |
OHMORI Tetsuo University of Tokushima. SCHOOL OF MEDICINE Professor, 医学部, 教授 (00221135)
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| Co-Investigator(Kenkyū-buntansha) |
KANEDA Yasuhiro University of Tokushima. UNIVERSITY HOSPITAL Assistant Professor, 医学部附属病院, 助手 (70325281)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Schizophrenia / Methamphetamine / Sensitization / Clozapine / Acetyicholine / Glutamate / GABA / Atypical neuroleptics / 抗精神病薬 / ドーパミン |
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| Research Abstract |
Repeated administration of methamphetamine results in schizophrenia-like psychosis in human and behavioral senslization in animals. Understanding of behavioral senslization may provide insight into the pathogenesis of both methamphetamine-induced psychosis and schizophrenia. It has been shown that NMDA antagonists block the development of sensitization, suggesting a role of glutamete in the phenomenon. In our previous project, we found that central cholinergic receptor and central phenomenon. In our previous project, we found that central cholinergic receptors and central GABA-benzodiazepine receptors also play an important role in the development of behavioral sensitization. In the present study, we showed that nitric oxide synthesis inhibition blocks the neurotoxicity induced by high doses of methamphetamine. These results as well as our previous results suggest that a neuronal circuit involving dopaminergic, cholinergic and GABAnergic pathways play an important role in the development of dehavioral sensitization.
Clozapine, a prototypical atypical neuroleptic, is a week dopamine d2 receptor blocker, but has many site of action and interfere with glutamatergic, cholinergic and GABAnergic function. Thus, it is assumed that the drug can blocks the development of sensitization by acting vatious sites in the neuronal circuit responsible for development of the phenomenon. Clinical studies on some other atypical neuroleptics were also conducted.
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