Involvement of amygdalar protein kinase A, but not calcium/calmodulin-dependent protein kinase II, in the reconsolidation of cocaine-related contextual memories in rats.
Involvement of amygdalar protein kinase A, but not calcium/calmodulin-dependent protein kinase II, in the reconsolidation of cocaine-related contextual memories in rats.
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DOI：
10.1007/s00213-013-3203-9
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发表时间：
2014-01
影响因子：
3.4
通讯作者：
Fuchs, Rita A.
中科院分区：
文献类型：
--
作者：
Arguello, Amy A.;Hodges, Matthew A.;Wells, Audrey M.;Lara, Honorio, III;Xie, Xiaohu;Fuchs, Rita A.
关键词：
对药物复发的情景控制依赖于成功地重新巩固和保留情景-反应-可卡因联系在长期记忆存储中。杏仁基底外侧核(BLA)在可卡因记忆再巩固和随后的药物环境诱导的可卡因寻找行为中起着关键作用；然而，对这一现象的细胞机制知之甚少。本研究评估了一种假说，即BLA中的蛋白激酶A(PKA)和钙/钙调蛋白依赖的蛋白激酶II(CaMKII)的激活对于促进随后的药物上下文诱导的可卡因寻找行为的上下文-反应-可卡因记忆的重新巩固是必要的。训练大鼠在不同的环境中杠杆按压注射可卡因，然后在不同的环境中进行消退训练。然后，大鼠被短暂地重新暴露在先前的可卡因配对环境或非配对环境中，以便分别重新激活与可卡因相关的上下文记忆并开始重新巩固它们，或者提供类似的行为体验，而不是明显地重新激活与可卡因相关的记忆。实验结束后，立即向BLA或后尾壳核(解剖控制区)内注入载体、PKA抑制剂RP-腺苷3‘，5’-环单硫代三乙基铵盐(RP-cAMPS)或CaMKII抑制剂KN-93。然后在可卡因配对环境和灭绝环境中测试大鼠的可卡因寻找行为(在之前的可卡因配对杠杆上的反应)。在可卡因记忆再巩固后，白血球内注射RP-cAMP，而不是KN-93，以剂量依赖、部位特异性和记忆再激活依赖的方式损害随后的可卡因寻找行为。PKA，而不是CaMKII，在BLA中的激活对可卡因记忆的重新稳定过程至关重要，该过程促进了随后的药物环境诱导的器质性可卡因寻找行为。
Contextual control over drug relapse depends on the successful reconsolidation and retention of context-response-cocaine associations in long-term memory stores. The basolateral amygdala (BLA) plays a critical role in cocaine memory reconsolidation and subsequent drug context-induced cocaine-seeking behavior; however, less is known about the cellular mechanisms of this phenomenon. The present study evaluated the hypothesis that protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII) activation in the BLA is necessary for the reconsolidation of context-response-cocaine memories that promote subsequent drug context-induced cocaine-seeking behavior. Rats were trained to lever-press for cocaine infusions in a distinct context, followed by extinction training in a different context. Rats were then briefly re-exposed to the previously cocaine-paired context or an unpaired context in order to reactivate cocaine-related contextual memories and initiate their reconsolidation or to provide a similar behavioral experience without explicit cocaine-related memory reactivation, respectively. Immediately after this session, rats received bilateral microinfusions of vehicle, the PKA inhibitor, Rp-Adenosine 3′,5′-cyclic monophosphorothioate triethylammonium salt (Rp-cAMPS), or the CaMKII inhibitor, KN-93, into the BLA or the posterior caudate putamen (anatomical control region). Rats were then tested for cocaine-seeking behavior (responses on the previously cocaine-paired lever) in the cocaine-paired context and the extinction context. Intra-BLA infusion of Rp-cAMPS, but not KN-93, following cocaine memory reconsolidation impaired subsequent cocaine-seeking behavior in a dose-dependent, site-specific, and memory reactivation-dependent fashion. PKA, but not CaMKII, activation in the BLA is critical for cocaine memory re-stabilization processes that facilitate subsequent drug context-induced instrumental cocaine-seeking behavior.
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影响因子：
5.2
作者：
Lee AM;Messing RO
通讯作者：
Messing RO
影响因子：
16.2
作者：
Miller, CA;Marshall, JF
通讯作者：
Marshall, JF
DOI：
10.1111/j.1460-9568.2009.06888.x
发表时间：
2009-09
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Fuchs RA;Bell GH;Ramirez DR;Eaddy JL;Su ZI
通讯作者：
Su ZI
影响因子：
2
作者：
Milton, Amy L.;Lee, Jonathan L. C.;Everitt, Barry J.
通讯作者：
Everitt, Barry J.
影响因子：
3.4
作者：
EHRMAN, RN;ROBBINS, SJ;OBRIEN, CP
通讯作者：
OBRIEN, CP