Opposite action of hippocampal CB1 receptors in memory reconsolidation and extinction
Opposite action of hippocampal CB1 receptors in memory reconsolidation and extinction
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DOI：
10.1016/j.neuroscience.2008.05.005
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发表时间：
2008-07-17
期刊：
影响因子：
3.3
通讯作者：
Quillfeldt, J. A.
中科院分区：
文献类型：
--
作者：
Alvares, L. De Oliveira;Genro, B. Pasqualini;Quillfeldt, J. A.
提取巩固的记忆会触发许多过程，这些过程取决于再激活阶段的持续时间，其中包括：再巩固需要一个短暂的再激活阶段，而消退则需要一个长时间的再激活阶段。本研究的范围是探讨海马内源性大麻素系统的再巩固和灭绝过程中的潜在作用。将CB 1大麻素受体拮抗剂N-（哌啶-1-基）-5-（4-碘苯基）-1-（2，4-二氯苯基）-4-甲基-1H-吡唑-3-甲酰胺（AM 251）双侧注入Wistar大鼠背侧海马CA 1区，在记忆再激活后促进了背景恐惧条件记忆的再巩固。DRB抑制同一脑区的蛋白质合成阻断了记忆的再巩固。这两种效应都是持续的，在第一次取回经验后持续长达7天。与此相反，局部输注的大麻素阻断记忆再巩固，这是拮抗大麻素与阈下剂量的CB 1拮抗剂的联合给药的效果，支持CB 1介导的作用，海马内源性大麻素系统的调制的记忆再巩固。局部注入AM 251到CA 1阻断记忆消退，而管理的anandamide促进它，然而，当结合阈下浓度的CB 1拮抗剂，anandamide没有影响的灭绝过程。在每种情况下观察到的明显相反的效果表明，海马内源性大麻素系统可能是一种开关机制，决定将发生哪些过程，要么保持原始记忆（重新巩固），要么促进新的学习（灭绝）。(C)2008年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Retrieval of a consolidated memory triggers a number of processes which depend, among other factors, on the duration of the reactivation session: reconsolidation requires a brief reactivation session, and extinction, a prolonged one. The scope of this study is to explore the potential role of the hippocampal endocannabinoid system on reconsolidation and extinction processes. Bilateral infusion of the CB1 cannabinoid receptor antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) into the CA1 region of the dorsal hippocampus of Wistar rats after memory reactivation facilitated the reconsolidation of the contextual fear conditioning memory. The inhibition of protein synthesis with DRB in the same brain region blocked memory reconsolidation. Both effects were persistent, lasting up to 7 days after the first retrieval experience. In contrast, the local infusion of anandamide blocked memory reconsolidation, an effect that was antagonized by the combined administration of anandamide with a subthreshold dose of a CB1 antagonist, supporting a CB1-mediated role of the hippocampal endocannabinoid system in the modulation of the memory reconsolidation. Local infusion of AM251 into CA1 blocked memory extinction whereas the administration of anandamide facilitated it; however, when combined with a subthreshold concentration of the CB1 antagonist, anandamide did not affect the extinction process. The clear-cut, opposite effects observed in each situation suggest a possible role of the hippocampal endocannabinoid system as a switching mechanism deciding which processes will take place, either maintaining the original memory (reconsolidation) or promoting a new learning (extinction). (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.