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Does amphetamine or methamphetamine become a drug good for diseases caused by dopamine deficiency, such as parkinson's disease : an experiment using knockout mice.

Research Project

Project/Area Number 09557037
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Legal medicine
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

YAMAMOTO Yoshiko  Kyoto Univ.Fac.of Med.Instructor, 医学研究科, 助手 (70025617)

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)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsAmphetamine / Methamphetamine / Cocaine / Parkinson's disease / Dopamine Transporter / Knockout mice / Locomotion / Concentration in the serum / KOマウス
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.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Y.Yamamoto: "Effects of methamphetamine on male fertility" Advances in Lega1 Medicine. 3. 493-494 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Yamamoto: "Effects of amphetamine on rat embryos developing in vitro" Reprod.Toxico1. 12. 133-137 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Yamamoto: "Developmental toxicological study of amphetamine using rat embryos cultured in vitro" Current Topics in Forensic Science. 2. 201-203 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Yamamoto: "Effect of Methamphetamine on Male Fertility" The Indo Pacific Association of Law Medicine and Science. 6. 657-660 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshiko Yamamoto et al.: "Effect of methamphetamine on male fertility" Advances in Legal Medicine. 3. 493-494 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshiko Yamamoto et al.: "Effects of amphetamine on rat embryos developing in vitro" Reprod.Toxicol. 12. 133-137 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshiko Yamamoto et al.: "Developmental toxicological study of amphetamine using rat embryos cultured in vitro" Current Topics in Forensic Science. 2. 201-203 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshiko Yamamoto et al.: "Effect of methamphetamine on male fertility" The Indo Pacific Association of Law, Medicine and Science. 6. 657-660 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Yamamoto: "Effects of methamphetamine on male fertility" Advances in Legal Medicine. 3. 493-494 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Yamamoto: "Effects of amphetamine on rat embryos developing in vitir" Reprod Toxicol. 12. 133-137 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Yamamoto: "Developmental toxicological study of amphetamine using rat embryos cultured in vitro" In Current Topics in Forensic Science. 2. 201-203 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Yamamoto: "Effect of Methamphetamine on Male Fertility" The Indo Pacific Association of Law Medicine and Science. 6. 657-660 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamamoto Y.: "Effects of amphetamine on rat embryos developing in vitro" Repro.Tox.(in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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