内生的なオピオイド回路は,国家依存の報酬消費を決定する

Daniel C Castro^1,2,3,4, Corinna S Oswell^5,6, Eric T Zhang^6,7

¹Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA. dcastro6@uw.edu.

Nature

|October 14, 2021

まとめ

研究者は報酬の消費を制御する重要な脳回路を特定しましたこの経路はムオピオイドペプチド受容体 (MOPR) と特定の投影を含み,オピオイドによる行動調節に関する新しい洞察を明らかにします.

科学分野:

神経科学
行動科学
薬理学について

背景:

ムオピオイドペプチド受容体 (MOPR) の刺激は呼吸,痛み緩和,報酬などの重要な機能に影響します.
薬物乱用や過剰摂取に MOPR 信号の調節不良が関与している.
MOPRが消費行動を制御する内生的なメカニズムは,ほとんど解明されていません.

研究の目的:

報酬の消費を規制する内生的なMOPRの規制メカニズムを調査する.
MOPR媒介による消費行動の制御に関与する特定の神経回路を特定する.

主な方法:

報酬消費のMOPR調節を研究するためにマウスモデルを使用した.
核アキュンベンスのプロジェクションを特定した.
核アキュンベンスの選択的調節を用いた.
CRISPR-Cas9遺伝子編集を適用してエンケファリン生成を妨害した.

主要な成果:

ネズミの報酬消費のMOPR規制は,背面ラフェから核アクンベンスの経路に依存することを発見した.
MOPRによるラフェ末端の阻害は,消費反応の制御に必要かつ十分であることを実証した.
報酬消費前に活性化したエンケファリンを含む核アキュンベンスの集合は,内生的なMOPRリガンド源として局所的なエンケファリンを示しています.

結論:

国家依存の消費行動に不可欠な内生性オピオイド回路を隔離しました
この回路は,特定の背面ラフェから核アクンベンスの投影と局所的なエンケファリン放出を含む.
報酬の経路を調節し,薬物乱用を治療するための新しい戦略を示唆しています.

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