| Project/Area Number |
17K15758
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied pharmacology
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
Saika Fumihiro 和歌山県立医科大学, 医学部, 助教 (10644099)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| 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 / CPPテスト / 再燃・再発 / 脳内炎症 / ドパミンアゴニスト / 再発 / ミクログリア / CPP試験 / 薬理学 / 行動実験 |
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| 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.
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| 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。
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