Elucidation of drug dependence formation / relapse molecular mechanism focusing on neuroinflammation

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K15758
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Wakayama Medical University
• Principal Investigator: Saika Fumihiro 和歌山県立医科大学, 医学部, 助教 (10644099)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 薬物依存 / 炎症 / ケモカイン / メタンフェタミン / コカイン / 前頭前皮質 / CPP / ドパミン

Outline of Final Research Achievements

Increased expression of several chemokines was observed in prefrontal cortex (PFC) after administration of addictive drugs. These chemokine receptor antagonists attenuated the increase in place preference due to addictive drugs. Next, the effect of dopamine signaling on chemokine expression in PFC was investigated. Increased chemokine expression as well as place preference by addictive drugs was attenuated by dopamine D1 receptor antagonist, but not dopamine D2 receptor antagonist. In addition, D1 receptor agonist showed increased chemokine expression in PFC and increased place preference. These results suggest that increased chemokine expression mediated by dopamine D1 receptor signals plays an important role in psychological dependence.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

近年、薬物乱用の若年化および多発する依存性薬物による重大な事件・事故により依存症の病態生理に基づく新規薬物治療戦略の確立は社会的な緊急課題となっている。薬物依存は中枢神経系における炎症の一つと位置付けられることより、未だに有効な治療薬が開発されていない薬物依存形成期や治療後においても様々な要因により再び乱用時と同様の渇望を生じる再燃・再発期におけるサイトカインやケモカインなどの炎症性メディエーターの関与を明らかにすることで今後の臨床応用へとつなげたい。