Generation and Characterization of MORIP Transgenic Mice

项目总结（见说明）： Mu阿片受体（莫尔）负责吗啡和相关药物的许多主要作用， 而莫尔与其他细胞信号分子的相互作用是本课题的重点。是 假设莫尔相互作用蛋白MORIPs对于调节莫尔是重要的，特别是当 关于阿片类药物依赖和成瘾。为了更好地了解MORIPs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MORIPs表达的影响 将使用一系列具有不同莫尔结合的激动剂 特性.将通过对GPR177转基因小鼠的研究来评估一种新的MORIP，GPR177。小鼠 将对其进行生物化学研究（MORIP和莫尔 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、埃托啡和丁丙诺啡的急性和慢性阿片样物质治疗。 我们还将检查纳洛酮沉淀的慢性吗啡治疗戒断的影响， 模型此外，我们将研究与慢性阿片类药物治疗相关的细胞表型，包括测量 树突状分支和神经发生。总体研究将阐明MORIPs的作用， 特别是GPR177在阿片类药物依赖相关的阿片类药物作用中的作用

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