Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan, ROC.
Behav Brain Res. 2010 Apr 2;208(2):522-7. doi: 10.1016/j.bbr.2009.12.034. Epub 2010 Jan 8.
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.
有人提出，每次记忆被检索时，记忆痕迹都会进入不稳定状态。重新激活的记忆依赖于新的蛋白质合成来进行准确的再巩固和恢复。因此，从理论上讲，与药物使用相关的持久和病理性记忆可以通过在记忆检索后立即使用蛋白质合成抑制剂来阻止其再巩固而被破坏。然而，抑制药物记忆再巩固的有效且高效的策略仍然难以捉摸。本研究旨在通过使用几种旨在重新激活先前获得的记忆的策略，检查全身环己酰亚胺和放线菌酮处理对重新激活可卡因条件性位置偏爱（CPP）的再巩固和维持的影响。我们发现，可卡因-CPP 重新激活后立即给予放线菌酮（50mg/kg/注射）和环己酰亚胺（15mg/kg/注射）可改善该记忆的后续表达和维持。同样，当在额外的可卡因和盐水条件作用试验后立即给予放线菌酮和环己酰亚胺时，这些额外训练试验引起的重新激活的记忆也减少了。然而，当在没有额外的盐水试验的情况下使用额外的可卡因条件作用试验时，类似的放线菌酮剂量方案未能影响随后可卡因-CPP 的表达。最后，在家笼中给予可卡因和盐水，无论是否给予放线菌酮治疗，对随后可卡因-CPP 的表达均无影响。总之，这些发现表明，可卡因-CPP 重新激活后立即给予全身蛋白质合成抑制剂治疗可有效减少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以平衡的方式给予额外的可卡因和盐水条件作用试验来实现。
