The role of glutamate receptor redistribution in locomotor sensitization to cocaine.
The role of glutamate receptor redistribution in locomotor sensitization to cocaine.
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DOI：
10.1038/npp.2009.190
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发表时间：
2010-02
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--
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重复可卡因暴露戒断后，延髓核（NAc）中AMPA受体（AMPAR）的表面表达增强。然而，目前尚不清楚这是否有助于表达运动敏感性，以及是否可以在其他纹状体区域观察到类似的变化。在这里，我们研究了NAc中AMPAR表面表达与运动敏化之间的关系。我们还研究了AMPAR在背外侧纹状体（DS）和NMDA受体（NMDAR）在NAc和DS的分布。停药后NAc的NMDAR分布有趋势，但无显著变化。DS中未观察到变化。最后一次暴露于可卡因后15天，NAc中AMPAR表面表达增加，但DS中减少。在戒断第14天再次暴露于可卡因降低了NAc中AMPAR表面表达24小时，但不是30分钟，在挑战后，但在DS中增加了24小时和30分钟。在与NAc中AMPAR表面表达增加或减少相关的时间评估运动致敏性。致敏的程度并没有随着AMPAR表面表达水平的变化而变化，也没有通过在可卡因攻击之前通过NAc内输注CNQX减少AMPAR传输而显著降低。基于我们的研究结果，和其他研究结果，我们认为，敏感的表达有没有明确的关系，改变AMPAR表面表达NAc虽然后者可能发挥作用，在增强追求和自我管理的药物观察致敏大鼠。
AMPA receptor (AMPAR) surface expression in the nucleus accumbens (NAc) is enhanced after withdrawal from repeated cocaine exposure. However, it is unclear whether this contributes to the expression of locomotor sensitization and whether similar changes can be observed in other striatal regions. Here we examined the relationship between AMPAR surface expression in the NAc and locomotor sensitization. We also examined AMPAR distribution in the dorsolateral striatum (DS) and NMDA receptor (NMDAR) distribution in the NAc and DS. Trends but no significant changes in NMDAR distribution were found in the NAc after withdrawal. No changes were observed in the DS. AMPAR surface expression was increased in the NAc 15 days after the last exposure to cocaine, but decreased in the DS. Re-exposure to cocaine on withdrawal day 14 decreased AMPAR surface expression in the NAc 24 h, but not 30 min, after challenge, but increased it in the DS 24 h and 30 min after challenge. Locomotor sensitization was evaluated at times associated with increased or decreased AMPAR surface expression in the NAc. The magnitude of sensitization did not vary with changes in the level of AMPAR surface expression, nor was it significantly reduced by decreasing AMPAR transmission via intra-NAc infusion of CNQX prior to cocaine challenge. Based on our results, and other findings, we suggest that the expression of sensitization has no clear relationship to altered AMPAR surface expression in NAc although the latter may play a role in the enhanced pursuit and self-administration of drugs observed in sensitized rats.
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