Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids
JournalJournal of Clinical Investigation
PublisherAmerican Society for Clinical Investigation
MetadataShow full item record
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.
SponsorsThis 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).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85063967898&doi=10.1172%2fJCI126912&partnerID=40&md5=464d7311b10f9903ec894294b828672d; http://hdl.handle.net/10713/10704