ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE/Akt-MAMMALIAN TARGET OF Rapamycin SIGNALING PATHWAY IN THE HIPPOCAMPUS IS ESSENTIAL FOR THE ACQUISITION OF MORPHINE-INDUCED PLACE PREFERENCE IN RATS
ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE/Akt-MAMMALIAN TARGET OF Rapamycin SIGNALING PATHWAY IN THE HIPPOCAMPUS IS ESSENTIAL FOR THE ACQUISITION OF MORPHINE-INDUCED PLACE PREFERENCE IN RATS
复制标题
海马中雷帕霉素信号通路磷脂酰肌醇 3-激酶/Akt-哺乳动物靶点的激活对于大鼠获得吗啡诱导的位置偏好至关重要。
DOI：
10.1016/j.neuroscience.2010.08.064
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发表时间：
2010-11-24
期刊：
影响因子：
3.3
通讯作者：
Liu, X. G.
中科院分区：
文献类型：
--
作者：
Cui, Yue;Zhang, X. Q.;Liu, X. G.
海马是吗啡诱导的条件性位置偏爱（CPP）获得的关键结构，CPP是评价药物奖赏的常用学习范式。然而，确切的机制在很大程度上仍然未知。磷脂酰肌醇3-激酶（PI 3 K）及其下游靶点包括Akt、哺乳动物雷帕霉素靶蛋白（mTOR）和70-kDa核糖体S6激酶（p70 S6 K），是与学习和记忆有关的关键分子。在此，我们检测了PI 3 K/Akt-mTOR-p70 S6 K信号通路在吗啡诱导的海马CPP中的作用。我们的研究结果表明，收购吗啡CPP增加Akt的磷酸化在海马CA 3区，但不是在脑桥核（NAc），腹侧被盖区（VTA）或CA 1。此外，磷酸化Akt仅在CA 3神经元中表达。同样，吗啡CPP后CA 3中磷酸化mTOR和p70 S6 K的水平显著增强。这些磷酸化蛋白的改变与吗啡CPP的获得呈正相关。更重要的是，在CA 3区微量注射PI 3 K抑制剂（LY 294002）或mTOR抑制剂（Rapamycin）可阻止CPP的获得，并抑制PI 3 K-Akt信号通路的激活。此外，将β-FNA（β-盐酸funalcidamine）（一种选择性不可逆μ阿片受体拮抗剂）预输注到CA 3中可显著阻止CPP的获得并损害Akt磷酸化。以上结果提示，海马CA 3区μ阿片受体激活的PI 3 K-Akt信号通路在吗啡诱导的CPP获得中起重要作用。(C)2010年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Hippocampus is a critical structure for the acquisition of morphine-induced conditioned place preference (CPP), which is a usual learning paradigm for assessing drug reward. However, the precise mechanisms remain largely unknown. Phosphatidylinositol 3-kinase (PI3K) and its downstream targets, including Akt, mammalian target of Rapamycin (mTOR) and 70-kDa ribosomal S6 kinase (p70S6K), are critical molecules implicated in learning and memory. Here, we tested the role of PI3K/Akt-mTOR-p70S6K signaling pathway in morphine-induced CPP in the hippocampus. Our results showed that the acquisition of morphine CPP increased phosphorylation of Akt in the hippocampal CA3, but not in the nucleus accumbens (NAc), the ventral tegmental area (VTA) or the CA1. Moreover, the phosphorylated Akt exclusively expressed in the CA3 neurons. Likewise, levels of phosphorylated mTOR and p70S6K were significantly enhanced in the CA3 following morphine CPP. The alterations of these phosphorylated proteins are positively correlated with the acquisition of morphine CPP. More importantly, microinjection of PI3K inhibitor (LY294002) or mTOR inhibitor (Rapamycin) into the CA3 prevented the acquisition of CPP and inhibited the activation of PI3K-Akt signaling pathway. In addition, pre-infusion of beta-FNA (beta-funaltrexamine hydrochloride), a selective irreversible mu opioid receptor antagonist, into CA3 significantly prevented the acquisition of CPP and impaired Akt phosphorylation. All these results strongly implied that the PI3K-Akt signaling pathway activated by mu opioid receptor in hippocampal CA3 plays an important role in acquisition of morphine-induced CPP. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.