Department of Experimental Psychology, University of Cambridge, Cambridge, United Kingdom.
Learn Mem. 2010 Aug 27;17(9):444-53. doi: 10.1101/lm.1757410. Print 2010 Sep.
A distributed limbic-corticostriatal circuitry is implicated in cue-induced drug craving and relapse. Exposure to drug-paired cues not only precipitates relapse, but also triggers the reactivation and reconsolidation of the cue-drug memory. However, the limbic cortical-striatal circuitry underlying drug memory reconsolidation is unclear. The aim of this study was to investigate the involvement of the nucleus accumbens core and the basolateral amygdala in the reconsolidation of a cocaine-conditioned stimulus-evoked memory. Antisense oligodeoxynucleotides (ASO) were infused into each structure to knock down the expression of the immediate-early gene zif268, which is known to be required for memory reconsolidation. Control infusions used missense oligodeoxynucleotides (MSO). The effects of zif268 knockdown were measured in two complementary paradigms widely used to assess the impact of drug-paired CSs upon drug seeking: the acquisition of a new instrumental response with conditioned reinforcement and conditioned place preference. The results show that both intranucleus accumbens core and intrabasolateral amygdala zif268 ASO infusions at memory reactivation impaired the reconsolidation of the memory underlying a cocaine-conditioned place preference. However, knockdown of zif268 in the nucleus accumbens at memory reactivation had no effect on the memory underlying the conditioned reinforcing properties of the cocaine-paired CS measured subsequently, and this is in contrast to the marked impairment observed previously following intrabasolateral amygdala zif268 ASO infusions. These results suggest that both the basolateral amygdala and nucleus accumbens core are key structures within limbic cortical-striatal circuitry where reconsolidation of a cue-drug memory occurs. However reconsolidation of memory representations formed during Pavlovian conditioning are differentially localized in each site.
一个分布式边缘皮质纹状体电路被牵连在提示诱导的药物渴望和复发中。暴露于药物配对的提示不仅会引发复发，还会触发提示-药物记忆的重新激活和再巩固。然而，药物记忆再巩固的边缘皮质-纹状体电路尚不清楚。本研究旨在探讨伏隔核核心和基底外侧杏仁核在可卡因条件刺激诱发记忆再巩固中的作用。反义寡核苷酸（ASO）被注入每个结构中，以敲低已知对记忆再巩固至关重要的即时早期基因 zif268 的表达。对照注入使用错义寡核苷酸（MSO）。通过两种广泛用于评估药物配对 CS 对药物寻求影响的互补范式来测量 zif268 敲低的效果：具有条件强化的新工具反应的获得和条件位置偏好。结果表明，在记忆再激活时，核伏隔核核心和核基底外侧杏仁核中的 zif268 ASO 输注均损害了可卡因条件位置偏好的记忆再巩固。然而，在记忆再激活时，核伏隔核中的 zif268 敲低对随后测量的可卡因配对 CS 的条件强化特性的记忆没有影响，这与先前观察到的基底外侧杏仁核 zif268 ASO 输注后明显受损形成鲜明对比。这些结果表明，基底外侧杏仁核和核伏隔核核心都是边缘皮质纹状体电路中发生提示-药物记忆再巩固的关键结构。然而，在每个部位，形成的条件性记忆的再巩固表现出不同的定位。
