Reduction in Responding for Sucrose and Cocaine Reinforcement by Disruption of Memory Reconsolidation.
Reduction in Responding for Sucrose and Cocaine Reinforcement by Disruption of Memory Reconsolidation.
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DOI：
10.1523/eneuro.0009-15.2015
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发表时间：
2015-03
期刊：
影响因子：
3.4
通讯作者：
Lee JL
中科院分区：
文献类型：
--
作者：
Exton-McGuinness MT;Lee JL
这项研究增加了越来越多的证据，证明工具性记忆（与世界互动的记忆）经历了重新巩固，这是一种以前认为不会经历重新巩固的记忆。此外，我们认为，可能有一个共同激活的D1 Rs和NMDARs的食欲记忆的不稳定和重新巩固的作用。储存的记忆是动态的，当重新激活时，可以经历一个不稳定和重新巩固的过程，以更新新的信息。重新巩固已被证明是各种实验设置;最近的学习工具记忆，一类记忆以前被认为不会经历重新巩固。在这里，我们在大鼠身上测试了在强化偶然性发生变化后，训练不足的按压记忆是否会不稳定。我们发现，在适当的条件下，对蔗糖和可卡因强化的按压记忆不稳定，并且这种记忆的再巩固被NMDA受体（NMDAR）拮抗剂[5 R，10 S]-[+]-5-甲基-10，1-二氢-5H-二苯并[a，d]环庚烯-5，10-亚胺（MK-801）的全身给药所损害。我们继续研究了延髓核（NAc）在蔗糖强化的工具记忆的再巩固中的潜在作用，表明共输注NMDAR拮抗剂2-氨基-5-磷酸戊酸（AP-5）和多巴胺-1受体（D1 R）拮抗剂7-氯-3-甲基-1-苯基-1，2，4，5-四氢-3-苯并氮杂卓-8-醇（SCH 23390）在记忆再激活前进入NAc损害再巩固;然而，当这些药物单独输注时没有影响。这种效果的进一步研究表明，联合输注破坏了记忆的巴甫洛夫成分的重新巩固，我们假设，共同激活的D1 R和NMDARs可能有助于食欲记忆的不稳定和重新巩固。我们的工作表明，弱训练的工具记忆经历类似的参数下，训练有素的重新巩固，也表明受体共激活的NAC可能有助于记忆不稳定。此外，它提供了一个重要的示范的治疗潜力，以巩固为基础的治疗，目标的工具组件的记忆在适应不良的药物寻求。
This research adds to the growing body of evidence that instrumental memories (memories of interactions with the world) undergo reconsolidation, a class of memory previously not thought to undergo reconsolidation. Furthermore, we suggest that there may be a role for coactivation of accumbal D1Rs and NMDARs in the destabilization and reconsolidation of appetitive memory. Stored memories are dynamic and, when reactivated, can undergo a process of destabilization and reconsolidation to update them with new information. Reconsolidation has been shown for a variety of experimental settings; most recently for well-learned instrumental memories, a class of memory previously thought not to undergo reconsolidation. Here we tested, in rats, whether a weakly-trained lever-pressing memory destabilized following a shift in reinforcement contingency. We show that lever-pressing memory for both sucrose and cocaine reinforcement destabilized under appropriate conditions, and that the reconsolidation of this memory was impaired by systemic administration of the NMDA receptor (NMDAR) antagonist [5R,10S]-[+]-5-methyl-10,1-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801). We went on to investigate the potential role of the nucleus accumbens (NAc) in the reconsolidation of sucrose-reinforced instrumental memories, showing that co-infusion of the NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP-5) and the dopamine-1 receptor (D1R) antagonist 7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol (SCH23390) into the NAc prior to memory reactivation impaired reconsolidation; however, there was no effect when these drugs were infused alone. Further investigation of this effect suggests the combined infusion disrupted the reconsolidation of pavlovian components of memory, and we hypothesize that coactivation of accumbal D1Rs and NMDARs may contribute to both the destabilization and reconsolidation of appetitive memory. Our work demonstrates that weakly-trained instrumental memories undergo reconsolidation under similar parameters to well-trained ones, and also suggests that receptor coactivation in the NAc may contribute to memory destabilization. Furthermore, it provides an important demonstration of the therapeutic potential of reconsolidation-based treatments that target the instrumental components of memory in maladaptive drug seeking.