Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids

@article{Cai:2019aa,

title = {Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids.},

author = {Ning-Sheng Cai and Cesar Quiroz and Jordi Bonaventura and Alessandro Bonifazi and Thomas O Cole and Julia Purks and Amy S Billing and Ebonie Massey and Michael Wagner and Eric D Wish and Xavier Guitart and William Rea and Sherry Lam and Estefania Moreno and Veronica Casado-Anguera and Aaron D Greenblatt and Arthur E Jacobson and Kenner C Rice and Vicent Casado and Amy Hauck Newman and John W Winkelman and Michael Michaelides and Eric Weintraub and Nora D Volkow and Annabelle M Belcher and Sergi Ferre},

url = {https://www.ncbi.nlm.nih.gov/pubmed/30913037},

doi = {10.1172/JCI126912},

issn = {1558-8238 (Electronic); 0021-9738 (Linking)},

year  = {2019},

date = {2019-03-26},

urldate = {2019-03-26},

journal = {J Clin Invest},

volume = {130},

abstract = {Identifying non-addictive opioid medications is a high priority in medical sciences, but mu-opioid receptors 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 mu-opioid receptors with galanin Gal1 receptors, rendering a profound decrease in the potency of methadone. This was explained by methadone's weaker proficiency to activate the dopaminergic system as compared to morphine and predicted a dissociation of therapeutic versus euphoric effects of methadone, which was corroborated by a significantly lower incidence of self-report of "high" in methadone-maintained patients. These results suggest that mu-opioid-Gal1 receptor heteromers mediate the dopaminergic effects of opioids that may lead to a lower addictive liability of opioids with selective low potency for the mu-opioid-Gal1 receptor heteromer, exemplified by methadone.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}