| Project/Area Number |
17591204
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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 | Hamamatsu University School of Medicine |
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Principal Investigator |
SEKINE Yoshimoto Hamamatsu Univ Sch of Med, Psychiatry and Neurology, Assistant Professor, 医学部, 助手 (70324358)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEI Noriyoshi Hamamatsu Univ Sch of Med, Psychiatry and Neurology, Associate Professor, 医学部, 助教授 (80206937)
MINABE Yoshio Hamamatsu Univ Sch of Med, Hamamatsu Univ Hospital, Psychiatry and Neurology, Lecturer, 医学部附属病院, 講師 (60181947)
NAKAMURA Kazuhiko Hamamatsu Univ Sch of Med, Hamamatsu Univ Hospital, Psychiatry and Neurology, Lecturer, 医学部附属病院, 講師 (80263911)
MORI Norio Hamamatsu Univ Sch of Med, Psychiatry and Neurology, Professor, 医学部, 教授 (00174376)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | addiction / methamphetamine / positron emission tomography / microglia / dopamine / ドパミン / 覚せい剤 / 炎症 / 覚せい剤関連精神障害 |
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| Research Abstract |
Methamphetamine (METH) is a popular addictive drug whose is associated with multiple neurological and psychiatric adverse events. The drug is also toxic to dopaminergic and serotonergic systems of the brain. Neuronal damage is associated with the increased expression of microglial cells that are thought to be involved in either pro-toxic or protective mechanisms in the brain. Although increased microgliosis has been observed in animal models of METH neurotoxicity, no study has reported on the status of microglial activation in human METH abusers. The present study reports on 12 abstinent METH abusers and 12 age-, gender-, education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [^<11>C] (R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([^<11>C] (R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials (BPs) of [11C](R)-PK11195 in brain regions innervated by dopaminergic and/or serotonergic projections. The mean levels of [^<11>C](R)-PK11195 binding were higher in METH abusers than those in control subjects in all brain regions (over 250% higher, p < 0.01 for all). In addition, [11C](R)-PK11195 BP levels were inversely related to the duration of METH abstinence in the midbrain (p < 0.01), striatum (p < 0.01), orbitofrontal cortex (p < 0.05), and insular cortex (p < 0.05). These results suggest that chronic self-administration of METH can cause reactive microgliosis in the brains of human METH abusers, a level of activation that appears to subside over longer periods of abstinence. Thus, early intervention with anti-inflammatory drugs that block microglial activation might offer therapeutic benefits to METH abusers.
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