脳内の転写因子デルタFosBの発現は,コカインに対する感受性を制御する

M B Kelz¹, J Chen, W A Carlezon

¹Laboratory of Molecular Psychiatry and Yale Center for Genes and Behavior, Yale University School of Medicine, New Haven, Connecticut 06508, USA.

Nature

|September 28, 1999

まとめ

慢性的にコカインに曝露すると,脳内のデルタFosBが持続的に増加します.

科学分野:

神経科学は神経科学である.
分子生物学は分子生物学である.
依存症の研究依存症の研究

背景:

急性コカイン曝露は,核アキュンベンスのFosタンパク質を一時的に誘導する.
慢性的なコカイン使用は,核アキュンベンスの持続的なデルタFosB発現につながります.
deltaFosBは,慢性的な薬物使用に関連した神経の可塑性に関与しています.

研究の目的:

慢性的なコカイン曝露の効果を媒介するデルタFosBの役割を調査する.
デルタFosB誘導が,コカインの報酬効果と運動運動効果に対する感受性を高めるかどうかを判断する.

主な方法:

誘導可能なデルタFosB発現を特定の中核アクンベンスのニューロンに誘導するためのトランスジェニックマウスを利用した.
行動反応と分子変化を評価するためにコカインを投与した.

主要な成果:

誘発されたデルタFosB発現は,コカインの報酬と運動運動活性化効果に対する反応性を高めました.
deltaFosB媒介の効果は,部分的にAMPAグルタミン酸受容体サブユニットGluR2発現の増加によるものでした.
核アクンベンスの持続的なデルタFosB蓄積は,持続的な行動の変化と相関しています.

結論:

deltaFosBは,コカインに対する感受性を高める上で重要な役割を果たします.
deltaFosBによる遺伝子発現の変化は,コカイン依存症の発達に寄与する可能性があります.
この転写因子は,中毒に対する潜在的な治療標的である.

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