Development of therapeutic method to suppress drug abuse by suppressing dopamine D1 signal

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10197
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kurume University
• Principal Investigator: Uematsu Ken 久留米大学, 医学部, 非常勤講師 (60441672)
• Co-Investigator(Kenkyū-buntansha): 西 昭徳 久留米大学, 医学部, 教授 (50228144) ; 首藤 隆秀 久留米大学, 医学部, 講師 (70412541)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: コカイン / S1Pレセプター / FTY720 / ドーパミンD1シグナル

Outline of Final Research Achievements

In this application study, we focused on the physiologically active lipid, sphingosine-1-phosphate (S1P), and analyzed the central nervous system action in basic researches. The present applicants analyzed the S1P analog molecule, the S1P receptor agonist, and fingolimod hydrochloride [FTY720], using protein phosphorylation as an index at the protein level, and demonstrated that dopamine D1 in medium striatal neurons of the mouse striatum. It was found that the effect of suppressing signal transduction is suppressed. This pharmacological action of FTY720 antagonized the addictive drugs (amphetamine, cocaine, etc.) due to the dopamine activating action, and the group of mice pre-administered with FTY720 was found to have suppressed locomotor hyperactivity due to cocaine administration.

Free Research Field

精神薬理学

Academic Significance and Societal Importance of the Research Achievements

薬物乱用、薬物依存は大きな社会問題であり社会的損失である。しかし、薬物乱用者、薬物依存者への治療は、精神療法、自助グループへの参加が主体であり、特効薬的治療薬は存在しない。本研究成果で、既に市販されている多発性硬化症治療薬、フィンゴリモド塩酸塩【FTY720】が、薬物依存症治療に応用可能性を持つデータが基礎動物実験で得られた。