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

Research Project

Project/Area Number 17K15758
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Applied pharmacology
Research InstitutionWakayama 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
Project Status Completed (Fiscal Year 2020)
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)
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
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.

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。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (26 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (18 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Chemogenetic Regulation of CX3CR1-Expressing Microglia Using Gi-DREADD Exerts Sex-Dependent Anti-Allodynic Effects in Mouse Models of Neuropathic Pain2020

    • Author(s)
      Fumihiro Saika, Shinsuke Matsuzaki, Daichi Kobayashi, Yuya Ideguchi, Tomoe Y Nakamura, Shiroh Kishioka, Norikazu Kiguchi
    • Journal Title

      Frontiers in Pharmacology

      Volume: 11 Pages: 925-925

    • DOI

      10.3389/fphar.2020.00925

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insufficient efferocytosis by M2-like macrophages as a possible mechanism of neuropathic pain induced by nerve injury.2020

    • Author(s)
      Kobayashi D, Kiguchi N, Saika F, Kishioka S, Matsuzaki S.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: Epub Issue: 1 Pages: 216-223

    • DOI

      10.1016/j.bbrc.2020.02.032

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] GRP receptor and AMPA receptor cooperatively regulate itch-responsive neurons in the spinal dorsal horn2020

    • Author(s)
      Kiguchi Norikazu、Uta Daisuke、Ding Huiping、Uchida Hitoshi、Saika Fumihiro、Matsuzaki Shinsuke、Fukazawa Yohji、Abe Manabu、Sakimura Kenji、Ko Mei-Chuan、Kishioka Shiroh
    • Journal Title

      Neuropharmacology

      Volume: 170 Pages: 108025-108025

    • DOI

      10.1016/j.neuropharm.2020.108025

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inflammatory Macrophages in the Sciatic Nerves Facilitate Neuropathic Pain Associated with Type 2 Diabetes Mellitus.2019

    • Author(s)
      Saika F, Kiguchi N, Matsuzaki S, Kobayashi D, Kishioka S.
    • Journal Title

      J Pharmacol Exp Ther.

      Volume: 368(3) Issue: 3 Pages: 535-544

    • DOI

      10.1124/jpet.118.252668

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] CXCL1 is responsible for cocaine-induced reward in mice.2018

    • Author(s)
      Saika F, Matsuzaki S, Kobayashi D, Kiguchi N, Kishioka S.
    • Journal Title

      Neuropsychopharmacol Rep

      Volume: 38(3) Pages: 145-148

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Upregulation of CCL7 and CCL2 in reward system mediated through dopamine D1 receptor signaling underlies methamphetamine-induced place preference in mice.2018

    • Author(s)
      Saika F, Kiguchi N, Wakida N, Kobayashi D, Fukazawa Y, Matsuzaki S, Kishioka S.
    • Journal Title

      Neurosci Lett.

      Volume: 665 Pages: 33-37

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of peripheral macrophages by nicotinic acetylcholine receptor agonists suppresses spinal microglial activation and neuropathic pain in mice with peripheral nerve injury2018

    • Author(s)
      Kiguchi N, Kobayashi D, Saika F, Matsuzaki S, Kishioka S
    • Journal Title

      J Neuroinflammation

      Volume: 15 Issue: 1 Pages: 96-96

    • DOI

      10.1186/s12974-018-1133-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacological Regulation of Neuropathic Pain Driven by Inflammatory Macrophages2017

    • Author(s)
      Kiguchi N, Kobayashi D, Saika F, Matsuzaki S, Kishioka S
    • Journal Title

      Int J Mol Sci

      Volume: 18 Issue: 11 Pages: 2296-2296

    • DOI

      10.3390/ijms18112296

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] DREADDシステムを用いたマクロファージ/ミクログリア機能制御が神経障害性疼痛モデルに及ぼす疼痛抑制効果2020

    • Author(s)
      雑賀 史浩、木口 倫一、小林 大地、出口 雄也、松﨑 伸介、岸岡 史郎
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] DREADDによるマクロファージ/ミクログリアの抑制は雄性マウスの神経障害性疼痛モデルにおいて抗アロディニア効果を示す2020

    • Author(s)
      出口 雄也、雑賀 史浩、木口 倫一、小林 大地、松﨑 伸介、岸岡 史郎
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 乾癬モデルマウスの痒みを担う脊髄内調節機構2019

    • Author(s)
      木口倫一、雑賀 史浩、松﨑 伸介、岸岡 史郎
    • Organizer
      136回日本薬理学会近畿部会
    • Related Report
      2019 Research-status Report
  • [Presentation] 神経障害性疼痛モデルマウスにおけるDREADDシステムを用いたマクロファージ/ミクログリア活性操作2019

    • Author(s)
      雑賀史浩、木口倫一、小林大地、松﨑伸介
    • Organizer
      疼痛学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Curcumin attenuates methamphetamine-induced conditioned place preference via inhibition of CC chemokine ligand 2 expression2018

    • Author(s)
      F. Saika, N. Kiguchi, D. Kobayashi, S. Matsuzaki , S. Kishioka
    • Organizer
      31th ECNP Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Possible involvement of chemokine ligands in addictive drugs-induced conditioned place preference in mice2018

    • Author(s)
      S. Kishioka, F. Saika, N. Kiguchi, D. Kobayashi, S. Matsuzaki
    • Organizer
      31th ECNP Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] α4β2ニコチン性アセチルコリン受容体アゴニストはマウスにおける2型糖尿病性神経障害性疼痛を減弱する2018

    • Author(s)
      F. Saika, N. Kiguchi, D. Kobayashi, S. Matsuzaki , S. Kishioka
    • Organizer
      第40回日本疼痛学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 炎症性マクロファージは神経傷害後のミクログリア活性化および機械的アロディニアを調節する2018

    • Author(s)
      木口倫一、雑賀史浩、小林大地、松崎伸介、岸岡史郎
    • Organizer
      第40回日本疼痛学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Inflammatory macrophages mediate neuropathic pain caused by type 2 diabetes mellitus2018

    • Author(s)
      N. Kiguchi, F. Saika, D. Kobayashi, S. Matsuzaki , S. Kishioka
    • Organizer
      第18回国際薬理学・臨床薬理学会議(WCP2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Inflammatory macrophages in the injured peripheral nerves facilitate spinal microglial activation and neuropathic pain in mice2018

    • Author(s)
      N. Kiguchi, F. Saika, D. Kobayashi, S. Matsuzaki , S. Kishioka
    • Organizer
      17th IASP World Congress of Pain
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 神経障害性疼痛に関与するマクロファージ/ミクログリアの機能解析2018

    • Author(s)
      雑賀史浩、木口倫一、小林大地、松崎伸介、岸岡史郎
    • Organizer
      第134回日本薬理学会近畿部会
    • Related Report
      2018 Research-status Report
  • [Presentation] Peripheral pro-inflammation cytokines participate in chronic morphine-induced hyperalgesia in mice.2017

    • Author(s)
      S. Kishioka, F. Saika, N. Kiguchi, S. Matsuzaki
    • Organizer
      CPDD
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 傷害神経に浸潤するマクロファージは脊髄ミクログリアの活性化を調節する2017

    • Author(s)
      木口倫一、雑賀史浩、小林大地、松崎伸介、岸岡史郎
    • Organizer
      第39回日本生物学的精神医学会・第47回日本神経精神薬理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] モルヒネ禁断時の血清コルチコステロン上昇におけるα4β2ニコチン性アセチルコリン受容体の関与2017

    • Author(s)
      岸岡史郎、山本千鶴子、小林大地、雑賀史浩、木口倫一、松崎伸介
    • Organizer
      第39回日本生物学的精神医学会・第47回日本神経精神薬理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 食餌性肥満に及ぼす脱酸梅果汁の抑制効果2017

    • Author(s)
      木口倫一、雑賀史浩、小林大地、松崎伸介、岸岡史郎
    • Organizer
      第15回果実酒・果実飲料と健康に関する研究
    • Related Report
      2017 Research-status Report
  • [Presentation] クルクミンによるメタンフェタミン誘発精神的依存形成の抑制2017

    • Author(s)
      雑賀史浩、木口倫一、小林大地、松崎伸介、岸岡史郎
    • Organizer
      第15回果実酒・果実飲料と健康に関する研究
    • Related Report
      2017 Research-status Report
  • [Presentation] 神経傷害後の末梢マクロファージによる脊髄ミクログリア調節作用2017

    • Author(s)
      木口倫一、小林大地、雑賀史浩、松崎伸介、岸岡史郎
    • Organizer
      第132回日本薬理学会近畿部会
    • Related Report
      2017 Research-status Report
  • [Presentation] Regulation of COPI vesicle transport via Scyl1 methylation under ER-stress2017

    • Author(s)
      S. Matsuzaki, G. Amano, Y.Mori, D. kobayashi, H. Takamura, K. Miyoshi, T. Yoshimura, F. Saika, N. Kiguchi, T. Katayama, S. Kishioka
    • Organizer
      ASCB2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2022-01-27  

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