| Project/Area Number |
13670852
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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 |
Pediatrics
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| Research Institution | Department of Pediatrics and Child Health, Kurume University School of Medicine |
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Principal Investigator |
YAMASHITA Yushiro Kurume University of Medicine, Assistant Professor, 医学部, 講師 (90211630)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUISHI Toyojiro Kurume University of Medicine, Professor, 医学部, 教授 (60157237)
NISHI Akinori Kurume University of Medicine, Assistant Professor, 医学部, 講師 (50228144)
YAMADA Shigeto Saga University of Medicine, Professor, 医学部, 教授 (20158190)
ISHIMATSU Masaru Kurume University of Medicine, Assistant Professer, 医学部, 講師 (90268839)
KITANI Yuri Kurume University of Medicine, Instructor, 医学部, 助手 (70341302)
石橋 正敏 (石橋 正俊) 久留米大学, 医学部, 助教授 (20168256)
岡村 尚昌 久留米大学, 文学部, 助手
石田 重信 久留米大学, 医学部, 講師 (30248405)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Attention deficit / hyperactivity disorder, dopamine / β-phenylethylamine / urine / methylphenidate / milnaciplan / locus ceruleus noradorenaline / treatment / メチルフェニデート / ミルナシプラン / 薬物療法 / 神経伝達物質 / 唾液 / MHPG / 薬物治療 / 非薬物療法 / 自閉性障害 / methylphenidate / monoamine oxidase B |
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| Research Abstract |
We measured the urine levels of β-phenylethylamine (PEA) and other monoamines to clarify the neurochemical mechanism in attention deficit hyperactivity disorder (ADHD). PEA levels were significantly lower in ADHD individuals (n=37) than in controls (n=21). The 22 children with ADHD were treated with methylphenidate. PEA levels significantly increased after methylphenidate therapy in responders (n=18), whereas they did not increase in non-responders. To develop new treatment for ADHD, we examined effects of milnaciplan (MIL), a selective serotonin and noradorenaline (NA) reuptake inhibitor, on the neuronal excitability and synaptic transmission in the rat locus ceruleus (LC) by intracellular and whole-cell patch-clamp recording techniques. We compared MIL and methylphenidate (MPH). Application of MPH and MIL to artificial CSF produced a hyperpolarizing response in LC neurons in a concentration-dependent manner. Spontaneous firing of LC neurons was blocked during the hyperpolarization. Under the whole-cell patch-clamp condition, prolonged application of MIL produced an outward current which lasted as long as MIL existed in the ACSF. The outward current induced by NA was enhanced by MIL in LC neurons. MIL enhanced the amplitude and duration of the inhibitory postsynaptic potential, while it depressed the excitatory postsynaptic potential. The results indicated that both MIL and MPH showed almost the same effects on neural activity and synaptic transmission in the rat LC. These results suggest that MIL increases the concentration of NA at synaptic cleft by inhibiting the NA reuptake system in the rat LC.
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