Activation of amygdaloid PKC pathway is necessary for conditioned cues-provoked cocaine memory performance
Activation of amygdaloid PKC pathway is necessary for conditioned cues-provoked cocaine memory performance
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DOI：
10.1016/j.nlm.2008.03.006
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发表时间：
2008-07-01
影响因子：
2.7
通讯作者：
Yu, Lung
中科院分区：
文献类型：
--
作者：
Lai, Yu-Ting;Fan, Hsin-Yi;Yu, Lung
药物相关线索在恢复药物服用行为中至关重要，即使在长期戒断期间，因此被认为是诱导药物渴望和导致复吸的关键因素。杏仁核复合体在调节情绪经验储存和情绪线索调节的记忆提取中具有重要的生理功能。本研究旨在探讨杏仁核基底外侧核及其胞内信号分子在药物线索诱发的可卡因记忆提取中的作用。提取实验前给予茴香霉素可显著抑制可卡因诱发的条件性位置偏爱记忆。同样，在测试前，通过将茴香霉素和放线菌酮输注到杏仁核的基底外侧核中，实现了对线索引起的可卡因CPP表现的类似阻断。杏仁核内注射蛋白激酶A抑制剂H89或MEK抑制剂U0126并不影响可卡因CPP记忆的恢复。相比之下，杏仁核内注射PKC抑制剂NPC 15437，可消除线索诱导的可卡因CPP表达，而记忆本身保持完整。杏仁核内输注NPC 15437似乎不影响自主活动或产生可观察到的厌恶效应。综上所述，我们的研究结果表明，PKC信号通路的激活和可能的杏仁核基底外侧核的下游从头蛋白质合成是必要的线索引起的可卡因记忆性能。然而，暂时抑制这一信号通路似乎并不影响可卡因CPP记忆本身。(C)2008年爱思唯尔公司All rights reserved.
Drug-associated cues are critical in reinstating the drug taking behavior even during prolonged abstinence and thus are thought to be a key factor to induce drug craving and to cause relapse. Amygdaloid complex has been known for its physiological function in mediating emotional experience storage and emotional cues-regulated memory retrieval. This study was undertaken to examine the role of basolateral nuclei of amygdala and the intracellular signaling molecule in drug cues-elicited cocaine memory retrieval. Systemic anisomycin treatment prior to the retrieval test abolished the cues-provoked cocaine conditioned place preference (CPP) memory. Likewise, a similar blockade of cues-provoked cocaine CPP performance was achieved by infusion of anisomycin and cycloheximide into the basolateral nuclei of amygdala before the test. Intra-amygdaloid infusion of H89, a protein kinase A inhibitor, or U0126, a MEK inhibitor, did not affect retrieval of the cues-elicited cocaine CPP memory. In contrast, intra-amygdaloid infusion of NPC 15437, a PKC inhibitor, abolished the cues-elicited cocaine CPP expression, while left the memory per se intact. Intra-amygdaloid infusion of NPC 15437 did not seem to affect locomotor activity or exert observable aversive effect. Taken together, our results suggest that activation of PKC signaling pathway and probably downstream de novo protein synthesis in the basolateral nuclei of amygdala is required for the cues-elicited cocaine memory performance. However, temporary inhibition of this signaling pathway does not seem to affect cocaine CPP memory per se. (C) 2008 Elsevier Inc. All rights reserved.