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Elucidation of brain mechanisms of drug addiction by visualization and artificial manipulation of neural circuits

Research Project

Project/Area Number 21H02799
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 51010:Basic brain sciences-related
Research InstitutionKobe University

Principal Investigator

Yoshihisa Tachibana  神戸大学, 医学研究科, 准教授 (50373197)

Co-Investigator(Kenkyū-buntansha) 金田 勝幸  金沢大学, 薬学系, 教授 (30421366)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2022: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2021: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Keywords依存症 / コカイン / ドーパミン / マウス / 大脳基底核 / 大脳皮質 / ニューロン / ミクログリア / イメージング / 腹側淡蒼球 / 光遺伝学 / 側坐核 / 淡蒼球 / 視床下核 / 腹側被蓋野
Outline of Research at the Start

薬物依存は精神と肉体を蝕み、自己のみならず家族をも不幸に巻き込む由々しき問題であり、社会的関心は非常に高い。しかしながら、薬物依存の病態メカニズムの解明は未だ十分でない。本研究では、情動と行動を繋ぐ脳部位である大脳基底核を中心とする薬物依存に関わる神経回路を考え、覚醒状態の齧歯類を用い、1)脳深部イメージング法により、薬物依存形成に拘わる神経回路動態を可視化する、2)その神経回路動態を基に、光遺伝学による人工神経活動操作を行い薬物探索行動の変容を導く、ことを目標とする。

Outline of Final Research Achievements

The term "addiction" has recently become ubiquitous in various forms of media. Among these, drug addiction stands out as a serious problem, affecting both the mental and physical issues of individuals and tragically entangling not only the afflicted individuals themselves but also their families in unhappiness. Consequently, social concern regarding this matter is notably high. However, despite this heightened awareness, our understanding of the pathophysiology of drug addiction remains unsolved. In this study, we aimed to elucidate the neural mechanisms underlying drug addiction by developing behavioral tasks in mice. Specifically, we focused on the pallidum, which is believed to be involved in reward-related behaviors, and investigated the response characteristics of pallidal neurons projecting to the subthalamic nucleus and the striatum in response to cocaine. Additionally, we extended our inquiry to examine the response of microglia within the brain to cocaine stimuli.

Academic Significance and Societal Importance of the Research Achievements

日本における薬物依存の研究、なかでも脳内メカニズムに関する基礎研究は数少ない。本研究によって明らかにされた、大脳皮質―大脳基底核神経回路における、神経細胞とグリア細胞を中心とした薬物依存の脳内メカニズムの機序は、ギャンブル・アルコールなど他の依存症の病態解明にもつながる。また、脳神経回路を人工的に操作することで、薬物依存症を治療すること、また予防法を導くことで、個人の健全な生活を維持させる効果のみならず、犯罪防止など負の社会的要素を除去するという点でもインパクトは大きいと期待される。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • Research Products

    (21 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 13 results,  Open Access: 7 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Int'l Joint Research] University of Bordeaux(フランス)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Social defeat stress enhances the rewarding effects of cocaine through α1A adrenoceptors in the medial prefrontal cortex of mice2024

    • Author(s)
      Saito Atsushi、Murata Haruka、Niitani Kazuhei、Nagasaki Junpei、Otoda Atsuki、Chujo Yusuke、Yanagida Junko、Nishitani Naoya、Deyama Satoshi、Kaneda Katsuyuki
    • Journal Title

      Neuropharmacology

      Volume: 242 Pages: 109757-109757

    • DOI

      10.1016/j.neuropharm.2023.109757

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of lipid synthesis in myelin modulates neural activity and is required for motor learning2023

    • Author(s)
      Kato D, Aoyama Y, Nishida K, Takahashi Y, Sakamoto T, Takeda I, Tatematsu T, Go S, Saito Y, Kunishima S, Cheng J, Hou L, Tachibana Y, Sugio S, Kondo R, Eto F, Sato S, Moorhouse AJ, Yao I, Kadomatsu K, Setou M, and Wake H.
    • Journal Title

      Glia

      Volume: 71 Issue: 11 Pages: 2591-2608

    • DOI

      10.1002/glia.24441

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cerebellar Nuclei Receiving Orofacial Proprioceptive Signals through the Mossy Fiber Pathway from the Supratrigeminal Nucleus in Rats2023

    • Author(s)
      Tsutsumi Yumi、Morita Yayoi、Sato Fumihiko、Furuta Takahiro、Uchino Katsuro、Sohn Jaerin、Haque Tahsinul、Bae Yong Chul、Niwa Hitoshi、Tachibana Yoshihisa、Yoshida Atsushi
    • Journal Title

      The Cerebellum

      Volume: - Issue: 5 Pages: 1795-1810

    • DOI

      10.1007/s12311-023-01602-9

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Role of neurotrophic and growth factors in the rapid and sustained antidepressant actions of ketamine2023

    • Author(s)
      Deyama Satoshi、Kaneda Katsuyuki
    • Journal Title

      Neuropharmacology

      Volume: 224 Pages: 109335-109335

    • DOI

      10.1016/j.neuropharm.2022.109335

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intranasal Administration of Resolvin E1 Produces Antidepressant-Like Effects via BDNF/VEGF-mTORC1 Signaling in the Medial Prefrontal Cortex2023

    • Author(s)
      Deyama Satoshi、Aoki Shun、Sugie Rinako、Fukuda Hayato、Shuto Satoshi、Minami Masabumi、Kaneda Katsuyuki
    • Journal Title

      Neurotherapeutics

      Volume: 20 Issue: 2 Pages: 484-501

    • DOI

      10.1007/s13311-022-01337-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Varenicline enhances recognition memory via α7 nicotinic acetylcholine receptors in the medial prefrontal cortex in male mice2023

    • Author(s)
      Esaki Hirohito、Deyama Satoshi、Izumi Shoma、Katsura Ayano、Nishikawa Keisuke、Nishitani Naoya、Kaneda Katsuyuki
    • Journal Title

      Neuropharmacology

      Volume: 239 Pages: 109672-109672

    • DOI

      10.1016/j.neuropharm.2023.109672

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of 5-HT1A receptors in the basolateral amygdala on 3,4-methylenedioxymethamphetamine-induced prosocial effects in mice2023

    • Author(s)
      Hirohito Esaki, Yuki Sasaki, Naoya Nishitani, Hikari Kamada, Satoko Mukai, Yoshitaka Ohshima, Sao Nakada, Xiyan Ni, Satoshi Deyama, Katsuyuki Kaneda
    • Journal Title

      European journal of pharmacology

      Volume: 946 Pages: 175653-175653

    • DOI

      10.1016/j.ejphar.2023.175653

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Noradrenergic stimulation of α1 adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice2023

    • Author(s)
      Niitani Kazuhei、Ito Shiho、Wada Shintaro、Izumi Shoma、Nishitani Naoya、Deyama Satoshi、Kaneda Katsuyuki
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 8089-8089

    • DOI

      10.1038/s41598-023-35242-0

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Cerebellar Cortex Receives Orofacial Proprioceptive Signals from the Supratrigeminal Nucleus via the Mossy Fiber Pathway in Rats2022

    • Author(s)
      Tsutsumi Yumi、Sato Fumihiko、Furuta Takahiro、Uchino Katsuro、Moritani Masayuki、Bae Yong Chul、Kato Takafumi、Tachibana Yoshihisa、Yoshida Atsushi
    • Journal Title

      The Cerebellum

      Volume: - Issue: 4 Pages: 663-679

    • DOI

      10.1007/s12311-022-01434-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Uts2b is a microbiota-regulated gene expressed in vagal afferent neurons connected to enteroendocrine cells producing cholecystokinin.2022

    • Author(s)
      Yuta Yoshioka, Yoshihisa Tachibana, Toshihiro Uesaka, Hiroyuki Hioki, Yuya Sato, Takumi Fukumoto, Hideki Enomoto.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 608 Pages: 66-72

    • DOI

      10.1016/j.bbrc.2022.03.117

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Piezo1/KLF15/IL-6 axis mediates immobilization-induced muscle atrophy2022

    • Author(s)
      Yu Hirata, Kazuhiro Nomura, Daisuke Kato, Yoshihisa Tachibana, Takahiro Niikura, Kana Uchiyama, Tetsuya Hosooka, Tomoaki Fukui, Keisuke Oe, Ryosuke Kuroda, Yuji Hara, Takahiro Adachi, Koji Shibasaki, Hiroaki Wake, Wataru Ogawa
    • Journal Title

      Journal of Clinical Investigation

      Volume: - Issue: 10 Pages: 1-13

    • DOI

      10.1172/jci154611

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efferent and afferent connections of supratrigeminal neurons conveying orofacial muscle proprioception in rats2021

    • Author(s)
      Yoshida Atsushi、Inoue Misaki、Sato Fumihiko、Morita Yayoi、Tsutsumi Yumi、Furuta Takahiro、Uchino Katsuro、Akhter Fatema、Bae Yong Chul、Tachibana Yoshihisa、Inoue Tomio
    • Journal Title

      Brain Structure and Function

      Volume: 227 Issue: 1 Pages: 111-129

    • DOI

      10.1007/s00429-021-02391-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pain induces stable, active microcircuits in the somatosensory cortex that provide a new therapeutic target.2021

    • Author(s)
      Okada T, Kato D, Nomura Y, Obata N, Quan X, Morinaga A, Yano H, Guo Z, Aoyama Y, Tachibana Y, Moorhouse AJ, Matoba O, Takiguchi T, Mizobuchi S and Wake H
    • Journal Title

      Sci Adv

      Volume: 7 Issue: 12 Pages: 8261-8261

    • DOI

      10.1126/sciadv.abd8261

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Movement disorders: the imbalance between hyperdirect and direct pathways in the basal ganglia.2024

    • Author(s)
      Tachibana Y
    • Organizer
      Bordeaux Neurocampus
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] The thalamo-insular cortical pathway is responsible for the expression of motor tics in mice.2024

    • Author(s)
      Kuno H, Tsuji N, Kobayashi K, Tachibana Y, and Takumi T.
    • Organizer
      Gordon Research Conference -Basal Ganglia-
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 口腔感覚の変調により不随意運動を改善する2023

    • Author(s)
      橘 吉寿
    • Organizer
      令和5年度日本大学歯学部大学院特別セミナー
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] マウスピースによるチック症改善とその作用機序2023

    • Author(s)
      橘 吉寿
    • Organizer
      第65回小児神経学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] The therapeutic effect and underlying mechanism of oral splint for ameliorating tic symptoms in patients with Tourette syndrome.2023

    • Author(s)
      Tachibana Y, Kuno H, Tsuji N, Yoshida A, and Takumi T.
    • Organizer
      SOCIETY FOR NEUROSCIENCE 53TH ANNUAL MEETING
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウスを用いたチック様症状発現に関わる脳神経回路の同定2021

    • Author(s)
      辻 奈津美、橘 吉寿、内匠 透
    • Organizer
      第113回近畿生理学談話会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Therapeutic effect and underlying mechanism of oral splint for ameliorating tic symptoms in patients with Tourette syndrome2021

    • Author(s)
      橘 吉寿、辻 奈津美、佐藤 文彦、内匠 透、吉田 篤
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-11-21  

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