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dc.contributor.authorCai, N.-S.
dc.contributor.authorQuiroz, C.
dc.contributor.authorBonaventura, J.
dc.date.accessioned2019-09-13T16:42:00Z
dc.date.available2019-09-13T16:42:00Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85063967898&doi=10.1172%2fJCI126912&partnerID=40&md5=464d7311b10f9903ec894294b828672d
dc.identifier.urihttp://hdl.handle.net/10713/10704
dc.description.abstractIdentifying nonaddictive opioid medications is a high priority in medical science, but μ-opioid receptors (MORs) mediate both the analgesic and addictive effects of opioids. We found a significant pharmacodynamic difference between morphine and methadone that is determined entirely by heteromerization of MORs with galanin Gal1 receptors (Gal1Rs), rendering a profound decrease in the potency of methadone. This finding was explained by the weaker proficiency of methadone in activating the dopaminergic system as compared with morphine and predicted a dissociation of the therapeutic and euphoric effects of methadone, which was corroborated by a significantly lower incidence of self-reports of feeling “high” in methadone-medicated patients. These results suggest that μ-opioid–Gal1R heteromers mediate the dopaminergic effects of opioids. The results further suggest a lower addictive liability of some opioids, such as methadone, due to their selective low potency for the μ-opioid–Gal1R heteromer.en_US
dc.description.sponsorshipThis study was supported by intramural funds from the NIDA and by grants from the Restless Legs Foundation; the Foundation for Science of the Therapeutic Experience; the University of Maryland MPowering the State Opioid Use Disorder initiative; the “Ministerio de Economía y Competitividad” with FEDER funds (SAF2017-87629-R); and the “Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas” (CB06/05/0064).en_US
dc.description.urihttps://doi.org/10.1172/JCI126912en_US
dc.language.isoen-USen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.relation.ispartofJournal of Clinical Investigation
dc.subject.meshMethadoneen_US
dc.subject.meshMorphineen_US
dc.subject.meshReceptor, Galanin, Type 1en_US
dc.titleOpioid-galanin receptor heteromers mediate the dopaminergic effects of opioidsen_US
dc.typeArticleen_US
dc.identifier.doi10.1172/JCI126912
dc.identifier.pmid30913037


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