ケタミンは側頭葉の破裂を阻害し,うつ病を迅速に緩和する

Yan Yang^1,2, Yihui Cui^1,2, Kangning Sang^1,2

¹Center for Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, School of Medicine, Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou 310058, China.

Nature

|February 16, 2018

まとめ

ケタミンは,N-メチル-d-アスパルテート受容体 (NMDAR) の活動を阻害することで,うつ病を迅速に緩和します. この作用はうつ病に繋がる異常な脳リズムを逆転させ新しい抗うつ薬の戦略を提示します

科学分野:

神経科学
精神科
薬理学について

背景:

ケタミンは,N-メチル-d-アスパルテート受容体 (NMDAR) 反抗剤であり,迅速な抗うつ効果を示しているが,そのメカニズムは不明である.
"反報酬センター"として知られる側頭部ヘブンヌラ (LHb) は,うつ病のモデルで変化した活動を表しています.

研究の目的:

ケタミンの迅速な抗うつ作用のメカニズムを解明する
うつ病とケタミンの作用における側頭葉の役割を調べる

主な方法:

ラットとマウスのうつ病モデルを使って
オプトジェネティクス,薬理学, コンピューターモデリング
LHbのニューロン爆発活動とテータバンド同期を測定した.

主要な成果:

抑うつ状態のような状態は,ケタミンによって逆転した,LHbのNMDAR依存の破裂とセータ同期を示した.
LHbニューロンの刺激は絶望と無快感を誘発した
LHbにおけるNMDARsまたはT型カルシウムチャネル (T-VSCC) をブロックすると,迅速な抗うつ効果が生じます.

結論:

ケタミンの抗うつ効果は,LHbの爆発活動を抑制することから生じる.
この阻害は下流のモノアミネルジック報酬経路を無効化する.
LHbを標的とした新型,迅速に作用する抗うつ剤の開発の枠組みを提供している.

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