絶滅によって引き起こされたAMPA受容体のアップレギュレーションは,コカイン探しの行動を減少させます
Michael A Sutton1, Eric F Schmidt, Kwang-Ho Choi
1Division of Molecular Psychiatry and the Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nature
|January 4, 2003
まとめ
コカイン依存症に対する絶滅訓練は,脳内のAMPAグルタミン酸受容体を増加させます. この神経可塑性は,ストレス下でもコカインの探求と再発を減らすのに役立ちます.
科学分野:
- 神経科学は神経科学である.
- 神経生物学 神経生物学とは
- 依存症の研究 依存症の研究
背景:
- コカイン依存症には,再発につながる持続的な神経生物学的な変化が含まれます.
- 抑制学習の形態である絶滅訓練は,報酬の欠如と薬物シグナルを関連付けることで,コカイン探しの行動を減らすことができます.
研究 の 目的:
- コカイン探求の減少における絶滅訓練の有効性を裏付ける神経生物学的メカニズムを調査する.
- 絶滅学習中の核アカンベンスの殻におけるAMPAグルタミン酸受容体の役割を決定する.
主な方法:
- 慢性的なコカインの自己投与に続いて,動物モデルでの離脱と絶滅訓練.
- AMPA受容体のサブユニット発現 (GluR1,GluR2/3) を核アキュンベンスの殻で測定した.
- ウイルスの媒介によるGluR1とGluR2の遺伝子過剰発現は,核アキュンベンスの殻にある.
主要な成果:
- 絶滅訓練は,核アクンベンスの殻にあるGluR1とGluR2/3のAMPA受容体サブユニットを増加させた.
- GluR1の発現の増加は,達成された絶滅の程度と正に相関していました.
- GluR1とGluR2の過剰発現は,コカイン探求の絶滅を容易にしたが,砂糖探求の絶滅を容易にしたわけではない.
- 過剰表現中の単一の絶滅セッションは,ストレス誘発の再発を弱めた.
結論:
- 核アキュンベンスの殻にあるAMPA受容体における絶滅誘発の可塑性は,コカイン探求に対するコントロールを容易にする.
- この可塑性は,グルタマタージックトーンを回復し,特にストレス下では,禁酒した人の再発傾向を軽減する可能性があります.
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