Systemic treatment with protein synthesis inhibitors attenuates the expression of cocaine memory
Systemic treatment with protein synthesis inhibitors attenuates the expression of cocaine memory
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DOI：
10.1016/j.bbr.2009.12.034
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发表时间：
2010-04-02
影响因子：
2.7
通讯作者：
Yu, Lung
中科院分区：
文献类型：
--
作者：
Fan, Hsin-Yi;Cherng, Chianfang G.;Yu, Lung
有人提出，记忆痕迹每次被提取时都会进入一个不稳定阶段。重新激活的记忆依赖于从头蛋白质合成，以忠实地重新巩固和恢复。因此，在理论上，与药物使用相关的长期和病理性记忆可以通过在记忆恢复后立即使用蛋白质合成抑制剂来抑制其再巩固而被破坏。然而，重新激活药物记忆的有效和高效的策略仍然难以捉摸。本研究采用几种旨在重新激活先前获得的记忆的策略，研究了全身性放线菌酮和茴香霉素治疗对重新激活的可卡因条件性位置偏爱（CPP）小鼠的再巩固和维持的影响。我们发现，茴香霉素（50毫克/公斤/注射）和放线菌酮（15毫克/公斤/注射）后立即给予可卡因-CPP的重新激活改善随后的表达和维持这种记忆。同样，当在额外的可卡因和盐水条件试验后立即给予茴香霉素和放线菌酮时，由这些额外的训练试验产生的重新激活的记忆也减少了。然而，一个类似的茴香霉素给药方案未能影响随后的可卡因-CPP的表达时，额外的可卡因条件试验中使用的额外的盐水试验。最后，可卡因和生理盐水给药的小鼠在他们的家笼与或没有茴香霉素治疗没有影响以后的可卡因-CPP的表达。总之，这些发现表明，可卡因-CPP重新激活后立即用蛋白质合成抑制剂进行全身治疗有效地减少了这种可卡因记忆的再巩固和维持。更重要的是，可卡因-CPP的重新激活可以通过呈现可卡因条件线索以及通过以平衡的方式施用额外的可卡因和盐水条件试验来实现。(C)2010 Elsevier B. V.保留所有权利。
It has been proposed that a memory trace enters a labile phase each time it is retrieved. A reactivated memory relies on de novo protein synthesis to be faithfully reconsolidated and restored. Thus, in theory, a long-lasting and pathological memory associated with drug use may be disrupted by inhibiting its reconsolidation through use of protein synthesis inhibitors administered immediately following the memory retrieval. However, effective and efficient strategies to reactivate drug memory remained elusive. This study was undertaken to examine the effects of systemic cycloheximide and anisomycin treatment on the reconsolidation and maintenance of a reactivated cocaine-conditioned place preference (CPP) in mice using several strategies designed to reactivate the previously acquired memory. We found that anisomycin (50 mg/kg/injection) and cycloheximide (15 mg/kg/injection) administered immediately after the reactivation of cocaine-CPP ameliorated subsequent expression and maintenance of this memory. Likewise, when anisomycin and cycloheximide were administered immediately after additional cocaine and saline conditioning trials, the reactivated memory engendered by those extra training trials was also diminished. However, a similar anisomycin dosing regimen failed to affect subsequent expression of cocaine-CPP when additional cocaine conditioning trial was used in the absence of additional saline trial. Finally, cocaine and saline administration to mice in their home cages with or without anisomycin treatment had no effect on later cocaine-CPP expression. Taken together, these findings suggest that systemic treatment with protein synthesis inhibitors immediately after the reactivation of cocaine-CPP effectively diminished the reconsolidation and maintenance of such a cocaine memory. More importantly, reactivation of cocaine-CPP could be achieved by presentation of cocaine-conditioned cues as well as by administering additional cocaine and saline conditioning trials in a balanced fashion. (C) 2010 Elsevier B.V. All rights reserved.