The Activation of NMDA Receptor-ERK Pathway in the Central Amygdala is Required for the Expression of Morphine-Conditioned Place Preference in the Rat
The Activation of NMDA Receptor-ERK Pathway in the Central Amygdala is Required for the Expression of Morphine-Conditioned Place Preference in the Rat
复制标题
中央杏仁核 NMDA 受体-ERK 通路的激活是大鼠吗啡条件位置偏好表达所必需的
DOI：
10.1007/s12640-011-9250-2
复制
发表时间：
2011-11-01
影响因子：
3.7
通讯作者：
Li, Chang-Qi
中科院分区：
文献类型：
--
作者：
Li, Fang;Wang, Xiao-Sheng;Li, Chang-Qi
成瘾药物的强化效应可以用条件化位置偏好(CPP)测验来评价，该测验既包括药物的作用，也包括环境线索。然而，编码的神经回路和潜在的信号机制还没有完全被理解。本研究采用大鼠吗啡-CPP模型，研究N-甲基-D-天冬氨酸(NMDA)受体和杏仁中央核(CEA)细胞外信号调节激酶(ERK)的磷酸化在吗啡诱导的CPP表达中的作用。我们发现，在训练后1天或7天，吗啡重复配对治疗引起了对与吗啡配对的明显偏好，这与CEA中ERK1/2磷酸化(p-ERK1/2，衡量ERK活性的指标)的增加有关。免疫荧光双标结果显示，80%以上的p-ERK1/2阳性神经元表达NMDA受体亚单位NR1。在CEA内注入MEK抑制剂U0126或NMDA受体拮抗剂MK-801，不仅可以抑制CEA中ERK1/2的激活，而且可以取消CPP的表达。这些结果表明，CEA中NMDA受体-ERK信号通路的激活是吗啡诱导的大鼠位置偏爱表达所必需的。
Reinforcing effects of addictive drugs can be evaluated with the conditioned place preference (CPP) test which involves both the action of drugs and environmental cues. However, the encoded neural circuits and underlying signaling mechanism are not fully understood. In this study, we have used morphine-CPP model in the rat and characterized the role of N-methyl-D-aspartate (NMDA) receptor and the phosphorylation of extracellular signal-regulated kinase (ERK) in the central nuclei of amygdala (CeA) in the expression of morphine-induced CPP. We have found that morphine repeated pairing treatment causes a significant preference for compartment paired with morphine after 1 day or 7 days post-training, which is associated with increased ERK1/2 phosphorylation (p-ERK1/2, a measure of ERK activity) in the CeA. More than 80% of the positive p-ERK1/2 neurons express NMDA receptor subunit NR1 by double immunofluorescence studies. The infusion of either MEK inhibitor U0126 or NMDA receptor antagonist MK-801 in the CeA not only suppresses the activation of ERK1/2 in the CeA but also abolishes the expression of CPP. These results suggest that the activation of the NMDA receptor-ERK signaling pathway in the CeA is required for the expression of morphine-induced place preference in the rat.