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Mechanisms and functional roles of drug-induced neuroplasticity in the brainstem cholinergic neurons

Research Project

Project/Area Number 24500432
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionHokkaido University

Principal Investigator

KANEDA Katsuyuki  北海道大学, 薬学研究科(研究院), 准教授 (30421366)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords薬物依存 / 神経可塑性 / 背外側被蓋核 / 腹側被蓋野 / 報酬系 / コカイン / シナプス可塑性 / ドパミン / 脳幹 / コリン作動性ニューロン
Outline of Final Research Achievements

The involvement and plasticity of the mesocorticolimbic dopamine (DA) system in cocaine-induced addiction have been studied extensively. However, it remains largely unexplored that the role of the brainstem cholinergic system in cocaine addiction. The laterodorsal tegmental nucleus (LDT) contains cholinergic neurons that innervate the ventral tegmental area (VTA) and is crucial for regulating the activity of VTA DA neurons, implying that LDT may also be associated with cocaine addiction. In this study, we found that cholinergic transmission from the LDT to the VTA is involved in acquisition and expression of cocaine-induced conditioned place preference and that, after repeated cocaine exposures, these neurons exhibit synaptic plasticity, which is dependent on NMDA receptor activation, nitric oxide production, and the activity of medial prefrontal cortex. The findings strongly suggest that LDT cholinergic neurons may be critically involved in developing cocaine-induced addiction.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (28 results)

All 2015 2014 2013 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (19 results) (of which Invited: 1 results) Remarks (3 results)

  • [Journal Article] Involvement and plasticity of brainstem cholinergic neurons in cocaine-induced addiction2014

    • Author(s)
      Kaneda K, Shinohara F, Kurosawa R, Taoka N, Ide S, Minami M
    • Journal Title

      Nihon Arukoru Yakubutsu Igakkai Zasshi

      Volume: 49(2) Pages: 92-103

    • NAID

      40022402944

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of cholinergic transmission from the laterodorsal tegmental nucleus to the ventral tegmental area in cocaine-induced place preference.2014

    • Author(s)
      Shinohara F, Kihara Y, Ide S, Minami M, Kaneda K
    • Journal Title

      Neuropharmacology

      Volume: 79 Pages: 573-579

    • DOI

      10.1016/j.neuropharm.2014.01.019

    • NAID

      120005367413

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cocaine exposure enhances excitatory synaptic drive to cholinergic neurons in the laterodorsal tegmental nucleus.2013

    • Author(s)
      Kurosawa R, Taoka N, Shinohara F, Minami M, Kaneda K
    • Journal Title

      Eur J Neurosci

      Volume: 38 Issue: 7 Pages: 3027-3035

    • DOI

      10.1111/ejn.12296

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] GABAergic mechanisms for shaping transient visual responses in the mouse superior colliculus.2013

    • Author(s)
      Kaneda K, Isa T
    • Journal Title

      Neuroscience

      Volume: 235 Pages: 129-140

    • DOI

      10.1016/j.neuroscience.2012.12.061

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Opposing roles of corticotropin-releasing factor and neuropeptide Y within the dorsolateral bed nucleus of the stria terminalis in the negative affective component of pain in rats2013

    • Author(s)
      Ide S, Hara T, Ohno A, Tamano R, Koseki K, Naka T, Maruyama C, Kaneda K, Yoshioka M, Minami M
    • Journal Title

      J. Neurosci

      Volume: 33 Issue: 14 Pages: 5881-5894

    • DOI

      10.1523/jneurosci.4278-12.2013

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transient enhancement of inhibition following visual cortical lesions in the mouse superior colliculus.2012

    • Author(s)
      Kaneda K
    • Journal Title

      European Journal of Neuroscience

      Volume: 36 Issue: 8 Pages: 3066-3076

    • DOI

      10.1111/j.1460-9568.2012.08224.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Plasticity in the brainstem neural circuit associated with drug addiction2015

    • Author(s)
      Kaneda K
    • Organizer
      第88 回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Intrinsic membrane plasticity in cholinergic neurons of the laterodorsal tegmental nucleus contributes to cocaine-induced addictive behavior2015

    • Author(s)
      上居寛典、黒澤諒、篠原史弥、田岡直史、南雅文、金田勝幸
    • Organizer
      第88 回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脳幹コリン作動性ニューロンにおける膜特性可塑的変化のコカイン探索行動における役割2014

    • Author(s)
      金田勝幸、上居寛典、黒澤諒、篠原史弥、田岡直史、南雅文
    • Organizer
      平成26年度アルコール・薬物依存関連学会合同学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-10-03 – 2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Intrinsic membrane plasticity induced after chronic cocaine administration in the laterodorsal tegmental nucleus dholinergic neuronc2014

    • Author(s)
      金田勝幸、黒澤諒、田岡直史、南雅文
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Chronic cocaine exposure changes inhibitory synaptic transmission in cholinergic neurons of the laterodorsal tegmental nucleus2014

    • Author(s)
      田岡直史、黒澤諒、南雅文、金田勝幸
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cholinergic transmission to and dopaminergic transmission from the ventral tegmental area contribute to the expression of cocaine-conditioned place preference2014

    • Author(s)
      篠原史弥、南雅文、金田勝幸
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] 背外側分界条床核における神経ペプチドを介した情報伝達の電気生理学的解析2014

    • Author(s)
      兼子朋之、原大樹、井手聡一郎、金田勝幸、南雅文
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] Chronic cocaine exposure induces inhibitory synaptic plasticity in cholinergic neurons of the laterodorsal tegmental nucleus2014

    • Author(s)
      田岡直史、黒澤諒、南雅文、金田勝幸
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2013 Research-status Report
  • [Presentation] 痛みによる不快情動生成における背外側分界条床核の役割2014

    • Author(s)
      井手聡一郎、金田勝幸、南雅文
    • Organizer
      日本薬学会 第134年会
    • Place of Presentation
      鶴屋百貨店東館(熊本)
    • Related Report
      2013 Research-status Report
  • [Presentation] コカイン慢性投与によるLDTコリン作動性ニューロンでのシナプス可塑性2013

    • Author(s)
      田岡直史、黒澤諒、篠原史弥、南雅文、金田勝幸
    • Organizer
      第27回北海道薬物作用談話会
    • Place of Presentation
      酪農学園大学(江別)
    • Related Report
      2013 Research-status Report
  • [Presentation] コカイン依存形成における背外側被蓋核-腹側被蓋野コリン作動性神経伝達の役割2013

    • Author(s)
      篠原史弥、木原由佳理、井手聡一郎、南雅文、金田勝幸
    • Organizer
      Neuro2013 (第36回日本神経科学大会・第56回日本神経化学会大会・第23回日本神経回路学会大会)
    • Place of Presentation
      国立京都国際会館(京都)
    • Related Report
      2013 Research-status Report
  • [Presentation] コカイン依存形成における背外側被蓋核から腹側被蓋野へのコリン作動性神経伝達の役割2013

    • Author(s)
      篠原史弥、木原由佳理、井手聡一郎、南雅文、金田勝幸
    • Organizer
      第23回日本臨床精神薬理学会・第43回日本神経精神薬理学会合同学会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄)
    • Related Report
      2013 Research-status Report
  • [Presentation] 背外側分界条床核におけるコルチコトロピン放出因子とニューロペプチドY神経情報伝達の電気生理学的解析2013

    • Author(s)
      井手聡一郎、原大樹、金田勝幸、南雅文
    • Organizer
      第23回日本臨床精神薬理学会・第43回日本神経精神薬理学会合同学会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄)
    • Related Report
      2013 Research-status Report
  • [Presentation] Opposing effects of corticotropin-releasing factor and neuropepetide Y on neuronal excitability in the dorsolateral bed nucleus of the stira terminalis2013

    • Author(s)
      Minami M, Hara T, Ide S, Kaneda K
    • Organizer
      Neuroscience2013 (SfN 43rd Annual Meeting)
    • Place of Presentation
      San Diego Convention Center (USA)
    • Related Report
      2013 Research-status Report
  • [Presentation] Role of cholinergic transmission from the laterodorsal tegmental nucleus to the ventral tegmental area in cocaine-induced place preference2013

    • Author(s)
      Kaneda K, Shinohara F, Kihara Y, Ide S, Minami M
    • Organizer
      Neuroscience2013 (SfN 43rd Annual Meeting)
    • Place of Presentation
      San Diego Convention Center (USA)
    • Related Report
      2013 Research-status Report
  • [Presentation] Role of cholinergic transmission from the laterodorsal tegmental nucleus to the ventral tegmental area in cocaine-induced addiction2013

    • Author(s)
      篠原史弥、木原由佳理、南雅文、金田勝幸
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Related Report
      2012 Research-status Report
  • [Presentation] Cocaine依存形成における背外側被蓋核の役割2012

    • Author(s)
      篠原史弥、木原由佳理、南雅文、金田勝幸
    • Organizer
      第26回北海道薬物作用談話会
    • Place of Presentation
      北海道大学(札幌)
    • Related Report
      2012 Research-status Report
  • [Presentation] Cocaineによる依存形成への脳幹コリン作動性ニューロンの関与2012

    • Author(s)
      篠原史弥、黒澤諒、木原由佳理、南雅文、金田勝幸
    • Organizer
      平成24年度アルコール・薬物依存関連学会合同学術総会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Related Report
      2012 Research-status Report
  • [Presentation] Cocaine-induced plasticity in cholinergic neurons of the laterodorsal tegmental nucleus2012

    • Author(s)
      Kaneda K, Kurosawa R, Minami M
    • Organizer
      42nd Society for Neuroscience Meeting
    • Place of Presentation
      New Orleans, Ernest N. Morial Convention Center (USA)
    • Related Report
      2012 Research-status Report
  • [Remarks] 薬物依存形成の脳内メカニズムの解明

    • URL

      http://www.pharm.hokudai.ac.jp/yakuri/study/03.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 北海道大学・大学院薬学研究院・薬理学研究室

    • URL

      http://www.pharm.hokudai.ac.jp/yakuri/index.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 北海道大学・大学院薬学研究院・薬理学研究室

    • URL

      http://www.pharm.hokudai.ac.jp/yakuri/index.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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