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Prevention of risperidone on MDMA((+)-3,4-methylenedioxymethamphetamine)-induced rise in core body temperature in rats and role of the serotonin 5-HT_<2A> receptor in the hyperthermic effects of MDMA

Research Project

Project/Area Number 16591157
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionJICHI MEDICAL UNIVERSITY

Principal Investigator

NISHIJIMA Kohichi  JICHI MEDICAL UNIVERSITY, School of Medicine, associate professor, 医学部, 助教授 (30198460)

Co-Investigator(Kenkyū-buntansha) TAKANO Kenji  JICHI MEDICAL UNIVERSITY, Medicine, professor, 医学部, 教授 (10197113)
HIRAI Nobuhide  JICHI MEDICAL UNIVERSITY, Medicine, associate professor, 医学部, 講師 (90333369)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2004: ¥3,300,000 (Direct Cost: ¥3,300,000)
KeywordsMDMA / hyperthermia / serotonin / dopamine / risperidone / serotonin 2A receptor / SCH 23390 / hyperthermia_ / rectal temperature / serotonin / dopamine / risperidone / SCH23390 / 5-HT 2A receptor / methamphetamine / dantrolene / hyperthermia
Research Abstract

MDMA (3,4-methylenidioxymetanphtamine) is a recreational drug that has become increasingly popular in Western countries. The use of MDMA by young people has increased in Japan. Life-threatening hyperthermia occurs with MDMA overdose. Since MDMA produces the acute and massive release of 5HT and DA from nerve endings, it is sometimes assumed that MDMA-induced hyperthermia is a consequence of 5HT and DA release and the subsequent stimulation of 5HT and DA receptors involved in thermoregulation. Considering these hypotheses, we investigated whether MDMA-induced hyperthermia is attenuated by risperidone, a potent DA and 5HT_2 receptor antagonist in rats. Risperidone 0.5mg/kg (other antagonists) or saline was intraperitoneally injected 15min prior to the subcutaneous administration of MDMA 10mg/kg, and rectal temperature was measured every 30min. MDMA induced an acute and strong increase in rectal temperature, but the increase in rectal temperature was significantly attenuated by pretreatment with risperidone from 30min until 120min after MDMA administration. The D_1 receptor antagonist SCH23390 attenuated MDMA-induced hyperthermia, but the D_2 receptor antagonist L-741626 failed to attenuate the hyperthermia. The 5TH_<1A> receptor antagonist WAY 100635 did not attenuate MDMA-induced hyperthermia. 5HT_<2A> receptor antagonist ritanserine attenuated the hyperthermia. The 5HT_<2C> antagonist SB242084 and 5HT_<2B/2C> antagonist SB206553 did not attenuate MDMA-induced hyperthermia. These results suggest that risperidone attenuated MDMA-induced hyperthermia due to D_1 and 5HT_<2A> receptor antagonist action, and that risperidone may be useful for the treatment of MDMA-induced hyperthermia.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (6 results)

All 2005

All Journal Article (6 results)

  • [Journal Article] ダントロレンのMDMAにおける高体温に対する有効性の検討2005

    • Author(s)
      塩田勝利, 西嶋康一, 岩村樹憲, 吉野達規, 久保島恭子, 加藤 敏
    • Journal Title

      日本神経精神薬理学雑誌 25

      Pages: 338-338

    • NAID

      10016943055

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SSRI(fluoxetine)と非定型坑精神病薬(perospirone)を併用した際のラット前頭葉セロトニン代謝に及ぼす影響2005

    • Author(s)
      吉野達規, 西嶋康一, 塩田勝利, 久保島恭子, 加藤 敏
    • Journal Title

      日本神経精神薬理学雑誌 25

      Pages: 297-297

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Effect of dantrolene on MDMA-induced hyperthermia in rats2005

    • Author(s)
      Shioda K, Nisijima K, Iwamura T, Yoshino T, Kuboshima K, Kato S
    • Journal Title

      Jpn J Neuropsychopharmacol 25

      Pages: 338-338

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Effect of fluoxetine and perospirone on serotonin levels in the rat medial frontal cortex2005

    • Author(s)
      Yoshino T, Nisijima K, Shioda K, Kuboshima K, Kato S
    • Journal Title

      Jpn J Neuropsychopharmacol 25

      Pages: 297-297

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SSRI(fluoxetine)と非定型抗精神病薬(perospirone)を併用した際のラット前頭葉セロトニン代謝に及ぼす影響2005

    • Author(s)
      吉野達規, 西島康一, 塩田勝利, 久保島恭子, 加藤敏
    • Journal Title

      日本神経精神薬理学雑誌 25

      Pages: 297-297

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ダントロレンのMDMAにおける高体温に対する有効性の検討2005

    • Author(s)
      塩田勝利, 西嶋康一, 岩村樹憲, 吉野達規, 久保島恭子, 加藤敏
    • Journal Title

      日本神経精神薬理学雑誌 25

      Pages: 338-338

    • NAID

      10016943055

    • Related Report
      2005 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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