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

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09197
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Asahikawa 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
• 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

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.

Free Research Field

法医学

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。