1998 Fiscal Year Final Research Report Summary
Does amphetamine or methamphetamine become a drug good for diseases caused by dopamine deficiency, such as parkinson's disease : an experiment using knockout mice.
| Project/Area Number |
09557037
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Legal medicine
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
YAMAMOTO Yoshiko Kyoto Univ.Fac.of Med.Instructor, 医学研究科, 助手 (70025617)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Hirosi Kyoto Univ.Fac.of Med.Instructor, 医学研究科, 助手 (60263092)
YAMAMOTO Keiichi Kyoto Univ.Fac.of Med.Associate Professor, 医学研究科, 助教授 (40025614)
FUKUI Yuko Kyoto Univ.Fac.of Med.Professor, 医学研究科, 教授 (10025588)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Amphetamine / Methamphetamine / Cocaine / Parkinson's disease / Dopamine Transporter / Knockout mice / Locomotion / Concentration in the serum |
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| Research Abstract |
Dopamine(DA) is an important neurotransmitter. Abused drugs such as cocaine(COC) and amphretamine(AMP) target the dopaminergic system by increasing DA concentrations in the extracellular space. Parkinson* disease is considered to be caused by deficiency of DA.The dopamine transporter (DAT) which is believed to control the temporal and spatial activity of released DA is an important element in regulating the action of DA.Therefore, the DAT can be a target for psychoactive drugs, such as AMP and cocaine, and may be related with the pathogenesis of parkinson* disease. The behavior of the DAT knockout mice is reported to resemble that of mice under the influence of AMP or cocaine. Thus, the action of AMP and cocain may be explained by a decreased level of DAT.We consider that AMP or cocaine may become a drug good for diseases caused by DA deficiency, such as parkinson* disease. DAT konckout mice are useful for testing the above hypothesis. First, we examined the effect of methamphetamine(MAMP) and COC on the locomotor acvtivity(LA) of wild-type mice using a LA recording system (Supermex). After MAMP was injected i.p. at a dose of 5 or 10 or 15 mg/kg, the LA was recorded every 20 min for a period of 24 hrs. The highest activity was recorded 20 mm after injection. The animals showed an elevated LA for 4-5 hrs. The LA returned to control levels 24 hrs after the injection. Locomotive activity was more elevated in a lower dose (5 mg/kg) than in a higher dose(15 mg/kg). This phenomenon was also observed with COC.The MAMP concentration in the serum was determined by HPLC.At a dose of 15 mg/kg, the peak concentration was reached at 5 mm after injection. The concentration reduced by half at 1 hr postinjection. Methamphetamine was not detected 24 hrs after injection.
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