Neuroscientific elucidation of the toxic mechanisms of new psychoactive drugs in the brain's reward system

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K10549
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 58040:Forensics medicine-related
• 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) ; 浅利 優 旭川医科大学, 医学部, 准教授 (40360979)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ジフェニジン / 危険ドラッグ / マイクロダイアリシス

Outline of Final Research Achievements

The effects of 4-methoxydiphenidine (4MeO-DPD) and 4-hydroxydiphenidine (4-OH-DPD) on the brain's reward system were investigated using in vivo brain microdialysis in rats.
An increase in spontaneous locomotor activity and dopamine concentration in the nucleus accumbens was observed following the administration of either 4MeO-DPD or 4-OH-DPD. The dopaminergic effects and brain concentration of 4MeO-DPD were significantly potentiated by P-glycoprotein inhibitors, whereas 4-OH-DPD was hindered by organic cation transporter inhibitors. These findings suggest that 4MeO-DPD and 4-OH-DPD are recognized by distinct transporters as substrates.

Free Research Field

法医学

Academic Significance and Societal Importance of the Research Achievements

新規向精神薬は、従来の違法薬物や麻薬の化学構造を組み変えたものが多く、元の薬物からは予想もできない強い毒性を持つ可能性があり、その毒性を事前に評価する事は、法医診断学上、大変重要である。未規制の新規向精神薬の毒性機序を解明し、既存の違法薬物（麻薬・覚せい剤、指定薬物を含む）の毒性と比較研究することは、法医診断学的に意義深い。