ハベヌラール α5 ニコチン受容体サブユニットは,シグナリングを制御し,ニコチン摂取量を制御する
Christie D Fowler1, Qun Lu, Paul M Johnson
1Laboratory for Behavioral and Molecular Neuroscience, Department of Molecular Therapeutics, The Scripps Research Institute-Scripps Florida, Jupiter, Florida 33458, USA.
Nature
|February 1, 2011
まとめ
CHRNA5の遺伝的変異は,喫煙中毒のリスクを高めます. 中央のヘブンヌラにあるα5ニコチンアセチルコリン受容体のサブユニットは,報酬システムを阻害することによって,ニコチンの摂取を制限する.
科学分野:
- 神経科学は神経科学である.
- 遺伝学 遺伝学とは
- 薬理学 薬理学とは
背景:
- CHRNA5の遺伝的変異は,たばこ依存症と肺がんに対する脆弱性の増加と関連しています.
- CHRNA5がニコチン摂取と中毒に影響を与える正確なメカニズムは,依然としてほとんど不明です.
研究 の 目的:
- ニコチンアセチルコリン受容体α5 (α5 nAChR) のニコチン摂取と関連する神経経路の調節における役割を明らかにする.
- ニコチンの作用をα5 nAChRs経由で媒介するヘブンヌロ-インターペドンキュラー (MHb-IPN) 経路の機能を調査する.
主な方法:
- Chrna5のノックダウンマウスとラットで,中枢ヘブネュラ (MHb) の標的型α5サブユニットノックダウンを用いた.
- ニコチンの摂取量,脳の報酬システム活動,ニコチンの投与後の骨格間核 (IPN) の活性化を評価した.
- ニコチンの報酬効果と抑制効果に対するMHbにおけるα5サブユニット発現の影響を調査した.
主要な成果:
- Chrna5 ノックアウトマウスは,ニコチン摂取量が大幅に増加した.
- ノックアウトされたマウスのMHbにおけるα5サブユニットの再発は,この効果を回復させ,ノックダウンされたマウスのノックダウンは,その効果を再現した.
- MHbにおけるα5サブユニットのノックダウンは,ニコチンの報酬効果を変えることなく,脳の報酬システムに対するより高いニコチン用量の抑制効果を廃止しました.
- ニコチン誘発のIPN活性化はα5ノックアウトマウスで減少し,IPNシグナリングを妨害するとネズミのニコチン摂取量が増加しました.
結論:
- ニコチンは,α5を含むnAChRを介してMHb-IPN経路を活性化します.
- この活性化は,ニコチン摂取を制限するために役立つ抑制的動機付け信号を誘発します.
- MHbのα5 nAChRは,ニコチンに対する脳の反応を調節することによって,タバコ依存の脆弱性を調節する上で重要な役割を果たします.
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