コカイン中毒への移行のセロトニン調節の基礎となるシナプスメカニズム

Yue Li^1,2, Linda D Simmler^1,2, Ruud Van Zessen^1,2

¹Department of Basic Neurosciences, Medical Faculty, University of Geneva, CH-1211 Geneva, Switzerland.

Science (New York, N.Y.)

|September 13, 2021

まとめ

セロトニン (5-HT) は依存症に重要な役割を果たしますこの研究はドーパミンだけでなくセロトニンが薬物依存症の行動に影響を及ぼすことを示しています

科学分野:

神経科学
薬理学について
依存症研究

背景:

薬物中毒の特徴は薬物中毒は薬物中毒は薬物中毒は
メソリンビック・ドーパミンのシグナル伝達が衝動的行動を誘発することが知られています
コカインのような精神刺激薬はまた,細胞外セロトニン (5-HT) の再吸収を抑制することで増加させます.

研究の目的:

薬物乱用への移行におけるセロトニン (5-HT) の役割を調査する.
セロトニンが依存関係のある行動に影響を与えるメカニズムを解明する.

主な方法:

コカイン不敏感のセロトニントランスポーターでSERT Met172ノックイン (SertKI) を使ったマウス.
SertKIと野生型のマウスの自己投与パラダイムでコカインを投与.
ドーパミン経路の光遺伝的刺激によりセロトニンのレベルを変化させる薬理学的操作を行いました
プロジェクション特異のセロトニン5-HT_1Bレセプターノックアウトマウスを生成した.

主要な成果:

SertKIマウスはコカインの自己投与への急速な移行を示し,5HTの役割を示した.
ドーパミン誘発による刺激で 5-HTの薬理学的な上昇は衝動的行動を逆転させました
セロトニンは,5-HT_1B受容体を通して,前皮質から背筋皮質のシナプスでプレシナプス抑制を誘導する.
5HT_1B受容体のノックアウトは,特定の予測では,強迫的なコカインの自己投与の発生率を増加させた.

結論:

セロトニンシグナル伝達は,特に5-HT_1B受容体を通して,薬物乱用への移行を大幅に調節します.
セロトニンが特定の皮質のシナプスに及ぼす作用は依存症の根本的なメカニズムです
これらの発見はセロトニンが新しい依存症治療の重要な標的であることを強調しています

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