IFENPRODIL ATTENUATES THE ACQUISITION AND EXPRESSION OF METHAMPHETAMINE-INDUCED BEHAVIORAL SENSITIZATION AND ACTIVATION OF RAS-ERK1/2 CASCADE IN THE CAUDATE PUTAMEN
IFENPRODIL ATTENUATES THE ACQUISITION AND EXPRESSION OF METHAMPHETAMINE-INDUCED BEHAVIORAL SENSITIZATION AND ACTIVATION OF RAS-ERK1/2 CASCADE IN THE CAUDATE PUTAMEN
复制标题
艾芬地尔减弱了尾壳核中甲基苯丙胺诱导的行为敏化和 RAS-ERK1/2 级联的获取和表达以及激活
DOI：
10.1016/j.neuroscience.2016.08.022
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发表时间：
2016-10-01
期刊：
影响因子：
3.3
通讯作者：
Liu, Xinshe
中科院分区：
文献类型：
--
作者：
Li, Lu;Qiao, Chuchu;Liu, Xinshe
长期不连续使用许多精神运动兴奋剂会导致行为过敏，并且由于其与复发具有共同的机制，大多数研究人员使用其动物模型来探索成瘾的神经生物学机制。最近的研究证明，N-甲基-D-天冬氨酸受体（NMDAR）与精神运动兴奋剂诱导的行为敏化有关。然而，含 GluN2B 的 NMDAR 的功能及其在甲基苯丙胺 (METH) 行为敏化的获取和表达中的潜在下游级联尚未被探索。在本研究中，使用 2.5、5 和 10 mg/kg GluN2B 特异性抑制剂艾芬地尔来探索这些受体在小鼠对 METH 行为致敏的不同阶段中的功能。然后，使用蛋白质印迹法检测前额皮质（PFc）、伏隔核（NAc）和尾壳核（CPu）中的Ras、pERK1/2/ERK1/2和Delta FosB水平。行为结果表明，低剂量艾芬地尔显着减弱了对冰毒行为过敏的获得和表达。蛋白质印迹分析显示，在采集过程中预注射低剂量艾芬地尔显着减弱了 METH 诱导的 CPu 中 Ras、pERK1/2/ERK1/2 和 DFosB 蛋白水平的上升。然而，表达预处理仅影响CPu中Ras和pERK1/2/ERK1/2水平的变化。此外，长期服用 METH 会增加 NAc 中的 pERK1/2/ERK1/2 水平。总之，含有 GluN2B 的 NMDAR 有助于小鼠对 METH 行为敏化的获得和表达。此外，获取阶段可能由CPu中的Ras-ERK1/2-DFosB级联介导，而表达阶段可能由CPu中的Ras-ERK1/2级联调节。 (C) 2016 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Chronic discontinuous use of many psychomotor stimulants leads to behavioral sensitization and, owing to it shares common mechanisms with relapse, most researchers use its animal model to explore the neurobiological mechanisms of addiction. Recent studies have proved that N-methyl-D-aspartate receptors (NMDARs) are implicated in psychomotor stimulant-induced behavioral sensitization. However, the function of GluN2B-containing NMDARs and their potential downstream cascade(s) in the acquisition and expression of behavioral sensitization to methamphetamine (METH) have not been explored. In this study, 2.5, 5, and 10 mg/kg ifenprodil, the specific inhibitor of GluN2B, was used to explore the function of these receptors in distinct phases of behavioral sensitization to METH in mice. Then, using western blot, Ras, pERK1/2/ERK1/2, and Delta FosB levels in the prefrontal cortex (PFc), nucleus accumbens (NAc), and caudate putamen (CPu) were detected. Behavioral results showed that low-dose ifenprodil attenuated the acquisition and expression of behavioral sensitization to METH significantly. Western blot analysis revealed that pre-injection of low-dose ifenprodil in the acquisition markedly attenuated METH-induced ascent of Ras, pERK1/2/ERK1/2, and DFosB protein levels in the CPu. However, pre-treatment in the expression only affected the alterations of Ras and pERK1/2/ERK1/2 levels in the CPu. Moreover, chronic METH administration increased pERK1/2/ERK1/2 level in the NAc. In conclusion, GluN2B-containing NMDARs contribute to both the acquisition and expression of behavioral sensitization to METH in mice. Furthermore, the acquisition phase might be mediated by the Ras-ERK1/2-DFosB cascade in the CPu while the expression phase may be regulated by the Ras-ERK1/2 cascade in the CPu. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.