000000508 001__ 508 000000508 005__ 20260219145619.0 000000508 0247_ $$2DOI$$a10.6083/M4736NWT 000000508 037__ $$aETD 000000508 245__ $$aOpioid agonists differentially engage and regulate mu opioid receptor desensitization, trafficking and recovery from desensitization 000000508 260__ $$bOregon Health and Science University 000000508 269__ $$a2010 000000508 336__ $$aThesis 000000508 502__ $$bPh.D. 000000508 502__ $$gNeuroscience 000000508 520__ $$aMorphine has a potency and efficacy for producing analgesia and a pharmacokinetic profile that make it favorable for use in pain treatment. Continued use of morphine and other opioids results in some degree of tolerance, such that the dose needs to be escalated to achieve the same effect. This can become problematic in the treatment of chronic pain, as elevated doses of opioids can produce unwanted side effects such as respiratory depression and dependence. Methadone, a synthetic agonist, is being increasingly used in the treatment of pain. In cancer patients, less dose escalation is required for those who are receiving sustained release methadone versus morphine. Thus the development of tolerance may differ depending on the agonist being used and understanding the adaptations that produce tolerance will be useful for pain treatment. The goal of this work is to understand the cellular mechanisms involved in desensitization and resensitization of mu opioid receptors in the locus coeruleus (LC) and how these processes are regulated by acute and long‐term administration of various opioids. To do this electrophysiological recording was used to measure mu opioid receptor (MOR) stimulated hyperpolarizations and 2‐photon imaging of epitope‐tagged receptors was used to monitor MOR trafficking in neurons in live brain slices. Desensitization and internalization induced by various agonists was examined in opiate naïve LC neurons. [Met5]‐enkephalin, methadone and etorphine resulted in both desensitization and internalization while oxycodone caused neither. Morphine 000000508 540__ $$fCC BY 000000508 542__ $$fIn copyright - single owner 000000508 650__ $$aArrestins$$031591 000000508 650__ $$aMethadone$$022132 000000508 650__ $$aMorphine$$022430 000000508 650__ $$aReceptors, Opioid, mu$$029979 000000508 650__ $$aSensory Receptor Cells$$025218 000000508 6531_ $$amethadone hydrochloride 000000508 691__ $$aSchool of Medicine$$041369 000000508 692__ $$aVollum Institute$$041509 000000508 7001_ $$aQuillinan, Nidia$$uOregon Health and Science University$$041354 000000508 7201_ $$aWilliams, John$$uOregon Health and Science University$$041354$$7Personal$$eAdvisor 000000508 8564_ $$909a45e93-e42d-4acd-9aea-e92e755e3c9a$$s1805491$$uhttps://digitalcollections.ohsu.edu/record/508/files/509_etd.pdf$$ePublic$$21ef3e0bcfd1584e98c22a4e86fd90839$$31 000000508 905__ $$a/rest/prod/bn/99/96/74/bn999674d 000000508 909CO $$ooai:digitalcollections.ohsu.edu:508$$pstudent-work 000000508 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument 000000508 980__ $$aTheses and Dissertations