Emergence of context-associated GluR(1) and ERK phosphorylation in the nucleus accumbens core during withdrawal from cocaine self-administration.
Emergence of context-associated GluR(1) and ERK phosphorylation in the nucleus accumbens core during withdrawal from cocaine self-administration.
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DOI：
10.1111/j.1369-1600.2010.00296.x
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发表时间：
2011-07
影响因子：
3.4
通讯作者：
Self DW
中科院分区：
文献类型：
--
作者：
Edwards S;Bachtell RK;Guzman D;Whisler KN;Self DW
再次暴露在与可卡因有关的环境中会促进寻求可卡因的复发，并对成功戒除构成持久的障碍。神经生物学适应被认为是在长期戒断期间保持寻求药物行为的基础，可能包括与可卡因配对环境特别相关的变化。我们在可卡因复发的动物模型中检测了大鼠纹状体亚区的GluR1S845和ERK磷酸化。有可卡因自我给药经历的动物及其连接的伴侣在停药一天或三周后在药物配对环境中暴露一小时，以在没有可卡因强化的情况下测量可卡因配对环境中诱导的蛋白质磷酸化。停药3周(而不是1天)后，自主给药组伏隔核核心GluR1S845(一种PKA活性指标)和ERK磷酸化增加，表明该伏隔核区上下文相关蛋白磷酸化的出现具有时间依赖性。相比之下，接受过自我给糖训练的动物在三周后再次暴露在蔗糖配对的环境中后，ERK表现出类似的增加，但GluR1S845没有显示出GluR1S845的磷酸化，这表明GluR1S845的磷酸化不仅仅是杠杆按压行为本身的结果。相比之下，基础(家笼)GluR1S845在伏隔核外壳和尾壳核中的磷酸化水平在戒断一天或三周可卡因后升高，无论背景如何。这些结果表明，伏隔核核心上下文相关的GluR1S845磷酸化的出现可能有助于可卡因寻找行为的持续，而ERK磷酸化可能是这种行为的结果。
Reexposure to cocaine-associated environments promotes relapse to cocaine seeking and represents a persistent impediment to successful abstinence. Neurobiological adaptations are thought to underlie the preservation of drug-seeking behavior during protracted withdrawal periods, possibly including changes associated specifically with cocaine-paired contexts. We measured GluR1S845 and ERK phosphorylation in rat striatal subregions in an animal model of cocaine relapse. Animals with cocaine self-administration experience and their yoked partners were exposed to extinction conditions for one hour in the drug-paired environmental context after one day or three weeks withdrawal to measure protein phosphorylation induced by the cocaine-paired context in the absence of cocaine reinforcement. GluR1S845 (an index of PKA activity) and ERK phosphorylation increased in the nucleus accumbens core of self-administering but not yoked animals after three weeks (but not one day) withdrawal, indicating a time-dependent emergence of context-associated protein phosphorylation in this accumbens subregion. In comparison, animals trained to self-administer sucrose displayed a similar increase in ERK, but not GluR1S845, phosphorylation following reexposure to a sucrose-paired environment three weeks later, indicating that GluR1S845 phosphorylation did not result solely from lever press behavior per se. In contrast, basal (home cage) GluR1S845 phosphorylation was elevated in the nucleus accumbens shell and caudate-putamen after one day or three weeks cocaine withdrawal regardless of context exposure. These results suggest that time-dependent emergence of context-associated GluR1S845 phosphorylation in the nucleus accumbens core may contribute to the persistence of cocaine-seeking behavior, whereas ERK phosphorylation may be a consequence of this behavior.
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影响因子：
16.2
作者：
Miller, CA;Marshall, JF
通讯作者：
Marshall, JF
影响因子：
3.4
作者：
EHRMAN, RN;ROBBINS, SJ;OBRIEN, CP
通讯作者：
OBRIEN, CP
影响因子：
25
作者：
Martin, Miquel;T Chen, Billy;Bonci, Antonello
通讯作者：
Bonci, Antonello
影响因子：
1.9
作者：
Cardinal, RN;Parkinson, JA;Everitt, BJ
通讯作者：
Everitt, BJ
影响因子：
4.7
作者：
Lu, L;Grimm, JW;Shaham, Y
通讯作者：
Shaham, Y