Opioid–galanin receptor heteromers differentiate the dopaminergic effects of morphine and methadone
Randal A. Serafini and Venetia Zachariou
Nash Family Department of Neuroscience and Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Address correspondence to: Venetia Zachariou, 1425 Madison Ave, Box 10-65, New York, New York 10029, USA. Phone: 212.659.8612; Email: venetia.zachariou@mssm.edu.
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Nash Family Department of Neuroscience and Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Address correspondence to: Venetia Zachariou, 1425 Madison Ave, Box 10-65, New York, New York 10029, USA. Phone: 212.659.8612; Email: venetia.zachariou@mssm.edu.
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First published May 28, 2019 - More info
J Clin Invest. 2019;129(7):2653–2654. https://doi.org/10.1172/JCI128987.
© 2019 American Society for Clinical Investigation
As the opioid addiction crisis reaches epidemic levels, the identification of opioid analgesics that lack abuse potential may provide a path to safer treatment of chronic pain. Preclinical studies have demonstrated that galanin affects physical dependence and rewarding actions associated with morphine. In the brain and periphery, galanin and opioids signal through their respective GPCRs, GalR1–3 and the μ-opioid receptor (MOR). In this issue of the JCI, Cai and collaborators reveal that heteromers between GalR1 and MOR in the rat ventral tegmental area attenuate the potency of methadone, but not other opioids, in stimulating the dopamine release that produces euphoria. These studies help us understand why some synthetic opioids, such as methadone, do not trigger the release of dopamine in the mesolimbic system but still possess strong analgesic properties.
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Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)