Generation and Characterization of MORIP Transgenic Mice

项目总结(见说明)： Mu阿片受体(MOR)负责吗啡和相关药物的许多主要作用， 而MOR与其他细胞信号分子之间的相互作用是本项目研究的重点。它是 假设MOR相互作用蛋白，MORIP，对MOR的调节很重要，特别是作为 关于阿片类药物依赖和成瘾。为了更好地了解MORIP在阿片类药物中的作用 药理学和依赖性、急性和阿片类药物治疗对已知MORIP表达的影响 在B6小鼠的区域大脑区域，将使用一系列具有不同MOR结合的激动剂进行评估 属性。一种新的MORIP，GPR177，将通过对GPR177转基因小鼠的研究进行评估。老鼠 GPR177分子的低表达和高表达将进行生化研究(MORIP和MOR 基因表达)和行为(阿片依赖表型和与一般阿片相关的表型 药理学)使用吗啡、依托啡和丁丙诺啡的急性和慢性阿片类药物治疗。 我们还将研究纳洛酮催促戒断慢性吗啡治疗的效果。 模特。此外，我们还将研究与慢性阿片类药物治疗相关的细胞表型，包括措施 树突状分枝和神经发生。总体研究将阐明MORIP的作用，以及 特别是在阿片类药物与阿片依赖相关的影响方面

PROJECT SUMMARY (See instructions): The Mu opioid receptor (MOR) is responsible for many of the major effects of morphine and related drugs, and the interaction between MOR and other cell signaling molecules is the focus of this project. It is hypothesized that MOR interacting proteins, MORIPs, are important for regulation of the MOR, especially as regards opioid dependence and addiction. In order to better understand the role of MORIPs in opioid pharmacology and dependence, the effects of acute and opioid treatment on expression of known MORIPs in regional brain areas of B6 mice will be assessed using a series of agonists with different MOR binding properties. A novel MORIP, GPR177, will be assessed through the study of GPR177 transgenic mice. Mice which underexpress and overexpress the GPR177 molecule will be studied biochemically (MORIP and MOR gene expression) and behaviorally (opioid dependence phenotypes and phenotypes related to general opioid pharmacology) using both acute and chronic opioid treatment with morphine, etorphine and buprenorphine. We will also examine the effects of naloxone-precipated withdrawal from chronic morphine treatment in this model. In addition we will study cellular phenotypes related to chronic opioid treatment including measures of dendritic arborization and neurogenesis. Overall studies will shed light on the role of MORIPs, and GPR177 in particular, in the effects of opioids related to opioid dependence