GPR3をニコチン離脱治療の開発の新しいアプローチとしてターゲットにする
Allison S Mogul1, Kendyl N Laumann1, Malia Bautista1
1Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
まとめ
新しいGタンパク質結合受容体3 (GPR3) アゴニストであるRTI-19318-32は,マウスのニコチン摂取を効果的に減少させ,新しいニコチン離脱療法の開発に希望を示しています.
科学分野:
- 神経科学
- 薬理学について
- 依存症 研究
背景:
- タバコの使用は,世界中で予防可能な死因の1つです.
- 現在のニコチン離脱補助薬は 長期的な効果が限られている.
- Gタンパク質結合受容体3 (GPR3) は,ニコチン依存症に不可欠な脳の領域で発現します.
研究 の 目的:
- ニコチン離脱の治療目標としてGPR3を研究する.
- ネズミのニコチン自己投与を減少させる新しいGPR3アゴニストRTI-19318-32の有効性を評価する.
主な方法:
- ニコチンを静脈内投与したマウスにRTI-19318-32を投与した.
- ニコチン摂取,食物補強,不安,移動に対するRTI-19318-32の影響を評価した.
- GPR3ノックアウトマウスを利用して,受容体の特異性を確認した.
- 中間ハベンヌラにおけるニコチンアセチルコリン受容体 (nAChR) サブユニットとGPR3の共同局所化を調べた.
主要な成果:
- RTI-19318-32は,雄性と雌性マウスの両方において,すべての試験用量においてニコチン摂取を著しく減少させた.
- この化合物はGPR3に対する選択性を示し,GPR3ノックアウトマウスにおけるニコチン摂取には影響はなかった.
- 高用量のRTI-19318-32は食品補強に影響を及ぼしたが,ベースラインの食品消費には影響を及ぼさなかったが,低用量のRTI-19318-32はニコチン摂取に選択的であった.
- GPR3の発現は,中央のヘブンヌラにおけるnAChRサブユニットと同局することが判明した.
結論:
- RTI-19318-32のようなアゴニストによるGPR3受容体の活性化は,ニコチン消費を減らすために機能的に有意である.
- GPR3はニコチン中断のための新薬の開発に 有望な治療目標です
- 特定の回路でGPR3の関与をターゲットにすることで,ニコチン消費への衝動を調節することができます.
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