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依存性のモデルにおける強迫性の基礎となるストカスティックシナプス可塑性
Vincent Pascoli1, Agnès Hiver1, Ruud Van Zessen1
1Department of Basic Neurosciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Nature
|December 21, 2018
まとめ
薬物中毒の特徴である 薬物中毒の特徴である 薬物中毒の特徴である 薬物中毒の特徴である 薬物中毒の特徴である 薬物中毒の特徴である このシナプス強化が 否定的な結果にも関わらず 持続的な有害物質使用の根底にあるのです
科学分野:
- 神経科学
- 依存症 研究
- 行動科学
背景:
- メソリンビック・ドーパミンは 行動を強化しますが 薬物乱用などの 慢性的な過剰刺激は 薬物乱用につながる可能性があります
- 薬物依存症を誘発する神経機構を理解することは 効果的な薬物依存症治療法の開発に不可欠です
研究 の 目的:
- ネズミのモデルで 強制的な強化の背後にある 神経回路を調査する
- 特定の脳の領域と シナプスの変化を 特定するために 処罰にもかかわらず 薬物探しの持続的な行動と関連付けます
主な方法:
- ネズミはオプトジェネティックにドーパミン神経を自己刺激させられ,罰 (電気ショック) を経験した.
- 背面のストライアトゥームのプロジェクションへの軌道前頭皮質 (OFC) の活動がモニターされた.
- この経路におけるシナプス可塑性 (増強と減強) を操作して,強迫的行動におけるその因果的役割を評価した.
主要な成果:
- 強迫的なレバープレッシャーは 依存症のような行動を示し 背中の状体端に OFC の活動が増加した
- OFC-striatal経路における永久的なシナプス増強は,強迫的行動を示すマウスで観察されました.
- このシナプス増強を in vivoで操作すると 強制的なレバープレッシングが誘発され,減強は逆転した.
結論:
- オービトフロントアル皮質から 背筋筋に伝達するシナプスの強化は 強制的な強化の重要な要因です
- この発見は 依存症の主要な症状に 基づく特定のシナプスメカニズムを示しています
- OFC-striatal synaptic plasticityをターゲットにすることで 依存症に対する新しい治療戦略が提供されるかもしれません
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