Changes in the Levels of p-ERK, p-CREB, and c-fos in Rat Mesocorticolimbic Dopaminergic System After Morphine-Induced Conditioned Place Preference: The Role of Acute and Subchronic Stress
Changes in the Levels of p-ERK, p-CREB, and c-fos in Rat Mesocorticolimbic Dopaminergic System After Morphine-Induced Conditioned Place Preference: The Role of Acute and Subchronic Stress
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DOI：
10.1007/s10571-013-0011-z
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发表时间：
2014-03-01
影响因子：
4
通讯作者：
Khodagholi, Fariba
中科院分区：
文献类型：
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作者：
Haghparast, Abbas;Fatahi, Zahra;Khodagholi, Fariba
ERK信号通路在细胞对环境变化的适应性反应中起着重要作用。应激条件可诱导神经细胞中活化ERK及其下游靶点CREB和c-fos的活化。服用阿片类药物也有同样的效果。本研究探讨了吗啡诱导的条件性位置偏爱（CPP）对中脑皮质边缘多巴胺能系统（NAc、AMY、Str和PFC）p-ERK/ERK比值、p-CREB/CREB比值和c-fos水平的影响。我们的目的是确定急性和亚慢性应激是否会影响这些变化。雄性Wistar大鼠分为两个盐水和吗啡治疗组。每组包括对照组、急性应激组和亚慢性应激组。对所有大鼠进行CPP程序。我们解剖出NAc，AMY，Str和PFC区域，并通过Western blot分析测量上述比率和c-fos水平。结果表明，生理盐水处理组动物在急性和亚慢性应激后，各因子均显著增强，但应激前额叶和纹状体p-ERK/ERK比值变化不显著;急性应激时，各因子变化不显著。条件反射评分在施加亚慢性而非急性应激后降低。在吗啡治疗的动物中，所有因素在应用急性和亚慢性应激后均增加，应激后条件反射评分也降低。我们的研究结果表明，在盐水或吗啡治疗的动物，急性和亚慢性应激增加p-ERK，p-CREB，和c-fos水平在中皮质边缘系统。已经表明，吗啡诱导上述因素的增强;另一方面，我们的结果表明，应激可以放大这些变化。
ERK pathway plays a critical role in the cellular adaptive responses to environmental changes. Stressful conditions can induce the activation of activate ERK, and its downstream targets, CREB and c-fos, in neural cells. Exposure to opioids has the same effect. In this study, we investigated the effects of morphine-induced conditioned place preference (CPP) on p-ERK/ERK ratio, p-CREB/CREB ratio and c-fos level in the mesocorticolimbic dopaminergic system including the nucleus accumbens (NAc), amygdala (AMY), striatum (Str), and prefrontal cortex (PFC). Our aim was to determine if acute and subchronic stress would affect these alterations. Male Wistar rats were divided into two saline-and morphine-treated groups. Each group contained of control, acute stress, and subchronic stress subgroups. The CPP procedure was performed for all of the rats. We dissected out the NAc, AMY, Str, and PFC regions and measured the mentioned ratios and c-fos level by Western blot analysis. The results revealed that in saline-treated animals, all factors enhanced significantly after performing acute and subchronic stress while there was an exception in p-ERK/ERK ratio in the Str and PFC; the changes were not significant during acute stress. Conditioning score decreased after applying the subchronic but not acute stress. In morphine-treated animals, all factors were increased after application of acute and subchronic stress, and conditioning scores also decreased after stress. Our findings suggest that in saline-or morphine-treated animals, acute and subchronic stress increases p-ERK, p-CREB, and c-fos levels in the mesocorticolimbic system. It has been shown that morphine induces the enhancement of the mentioned factors; on the other hand, our result demonstrates that stress can amplify these changes.