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Evaluation of the neurochemical effects of diphenidine, a new psychoactive substance, on the dopaminergic reward system by using rat brain microdialysis

Research Project

Project/Area Number 16K09197
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Legal medicine
Research InstitutionAsahikawa Medical College

Principal Investigator

SHIMIZU Keiko  旭川医科大学, 医学部, 教授 (90312462)

Co-Investigator(Kenkyū-buntansha) 奥田 勝博  旭川医科大学, 医学部, 助教 (00389115)
田中 宏樹  旭川医科大学, 医学部, 助教 (70596155)
Research Collaborator ASARI Masaru  
MATSUBARA Kazuo  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsジフェニジン / 危険ドラッグ / マイクロダイアリシス / 薬物依存 / 側坐核 / ドパミン / ダイアリシス
Outline of Final Research Achievements

Diphenidine (DPD) ,one of the new psychoactive substances, stimulated A10 nervous system which is projected from ventrotegmental area to limbic system (nucleus accumbens, hippocampus, amygdala etc.) and to medial prefrontal cortex rather than A9 nervous system which is projected from substantia nigra to striatum. DPD was detected in the dialysate from rat brain after i.p. injection. The highest concentrations were observed at 30 minutes and the concentrations were decreased time-dependent manner. The DPD concentration in the dialysate was significantly increased by pretreatment of P-glycoprotein inhibitors and also an organic cation transporter inhibitor. However, no difference was identified between DPD levels in the blood of the inhibitors and saline pretreatment groups. The results indicated that P-glycoprotein and organic cation transporter has an important role in the transportation of DPD across the blood-brain barrier.

Academic Significance and Societal Importance of the Research Achievements

ジフェニジンの毒性機序を解明し、既存の違法薬物(覚せい剤や麻薬)の毒性と比較研究することは、法医診断学的に意義深い。ジフェニジンの中枢毒性に関する詳細な神経科学的検討は、未だ報告されていなかった。ジフェニジンを含め、基本構造で分類される様々なタイプの危険ドラッグの血液脳関門通過様式及びその依存毒性を明らかにすることは、今後も出現が続くと予想される新規危険ドラッグの毒性機序を推定・検討する上でも極めて有用である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2018 2017

All Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] Mechanistic study of diphenidine, a new psychoactive substance, for the neurochemical effect by using rat brain microdialysis2018

    • Author(s)
      Katsuhiro Okuda, Masaru Asari, Hiroki Tanaka, Shotaro Isozaki, Hiromi Yamada, Kie Horioka, Ayaka Yoshida, Kazuo Matsubara, Hiroshi Shiono, Keiko Shimizu
    • Organizer
      24th Congress of the International Academy of Legal Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Evaluation of the neurochemical effects of diphenidine, a new psychoactive substance, on the dopaminergic reward system by using rat brain microdialysis2017

    • Author(s)
      Okuda K, Tanaka H, Asari M, Horioka K, Matsubara K, Shiono H, Shimizu K
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ラット脳マイクロダイアリシスによるジフェニジンの脳内報酬系への影響評価2017

    • Author(s)
      奥田勝博, 田中宏樹, 浅利 優, 堀岡希衣, 早川 輝, 磯崎翔太郎, 吉田あやか, 松原和夫, 塩野 寛, 清水惠子
    • Organizer
      第101次日本法医学会学術全国集会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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