Basolateral amygdala cdk5 activity mediates consolidation and reconsolidation of memories for cocaine cues.
Basolateral amygdala cdk5 activity mediates consolidation and reconsolidation of memories for cocaine cues.
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基底外侧杏仁核 Cdk5 活性介导可卡因线索记忆的巩固和再巩固
DOI：
10.1523/jneurosci.2112-10.2010
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发表时间：
2010-08-04
期刊：
影响因子：
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通讯作者：
Lu L
中科院分区：
文献类型：
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作者：
Li FQ;Xue YX;Wang JS;Fang Q;Li YQ;Zhu WL;He YY;Liu JF;Xue LF;Shaham Y;Lu L
可卡因的使用和复发涉及可卡因相关的环境背景和离散刺激和可卡因效应之间的学习关联。最初，这些上下文和离散的线索在与可卡因接触配对后经历记忆巩固。在戒断期间，可卡因线索记忆可以在没有药物的情况下经历线索暴露后的记忆重新巩固。我们采用条件性位置偏爱（CPP）程序在大鼠研究神经元蛋白激酶细胞周期蛋白依赖性激酶5（Cdk 5）在巩固和再巩固可卡因线索记忆的作用。我们发现，可卡因CPP的表达在无药物测试后1天CPP训练（四对10毫克/公斤可卡因与一个上下文和四对生理盐水与不同的上下文）增加Cdk 5活性，和水平的Cdk 5激活剂p35在基底外侧，但不是中央杏仁核。我们还发现，在训练期间可卡因背景配对后立即（但不是6小时）向基底外侧（而不是中央）杏仁核注射Cdk 5抑制剂β-丁内酯（100 ng/侧），可阻止随后的可卡因CPP表达。训练后，在测试前即刻急性基底外侧（而非中央）杏仁核β-丁内酯注射阻止了可卡因CPP的表达;在1天后进行的第二次测试中也观察到了这种效应，表明对可卡因线索记忆的再巩固有影响。作为支持，在单次暴露于可卡因配对环境后立即（但不是6小时）给予基底外侧β-丁内酯注射，可在注射后1天和14天阻止可卡因CPP表达。结果表明，基底外侧杏仁核Cdk 5活性的可卡因相关的环境线索的记忆的巩固和再巩固是至关重要的。
Cocaine use and relapse involves learned associations between cocaine-associated environmental contexts and discrete stimuli and cocaine effects. Initially, these contextual and discrete cues undergo memory consolidation after being paired with cocaine exposure. During abstinence, cocaine cue memories can undergo memory reconsolidation after cue exposure without the drug. We used a conditioned place preference (CPP) procedure in rats to study the role of neuronal protein kinase cyclin-dependent kinase 5 (Cdk5) in consolidation and reconsolidation of cocaine cue memories. We found that the expression of cocaine CPP in drug-free tests 1 d after CPP training (four pairings of 10 mg/kg cocaine with one context and four pairings of saline with a different context) increased Cdk5 activity, and levels of the Cdk5 activator p35 in basolateral but not central amygdala. We also found that basolateral (but not central) amygdala injections of the Cdk5 inhibitor β-butyrolactone (100 ng/side) immediately (but not 6 h) after cocaine–context pairings during training prevented subsequent cocaine CPP expression. After training, acute basolateral (but not central) amygdala β-butyrolactone injections immediately before testing prevented the expression of cocaine CPP; this effect was also observed on a second test performed 1 d later, suggesting an effect on reconsolidation of cocaine cue memories. In support, basolateral β-butyrolactone injections, given immediately (but not 6 h) after a single exposure to the cocaine-paired context, prevented cocaine CPP expression 1 and 14 d after the injections. Results indicate that basolateral amygdala Cdk5 activity is critical for consolidation and reconsolidation of the memories of cocaine-associated environmental cues.