Generation and Characterization of MORIP Transgenic Mice

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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