Mu opioid receptors in GABAergic neurons of the forebrain promote alcohol reward and drinking

Addiction Biology
Sami Ben HamidaBrigitte L Kieffer

Abstract

Mu opioid receptors (MORs) are widely distributed throughout brain reward circuits and their role in drug and social reward is well established. Substantial evidence has implicated MOR and the endogenous opioid system in alcohol reward, but circuit mechanisms of MOR-mediated alcohol reward and intake behavior remain elusive, and have not been investigated by genetic approaches. We recently created conditional knockout (KO) mice targeting the Oprm1 gene in GABAergic forebrain neurons. These mice (Dlx-MOR KO) show a major MOR deletion in the striatum, whereas receptors in midbrain (including the Ventral Tegmental Area or VTA) and hindbrain are intact. Here, we compared alcohol-drinking behavior and rewarding effects in total (MOR KO) and conditional KO mice. Concordant with our previous work, MOR KO mice drank less alcohol in continuous and intermittent two-bottle choice protocols. Remarkably, Dlx-MOR KO mice showed reduced drinking similar to MOR KO mice, demonstrating that MOR in the forebrain is responsible for the observed phenotype. Further, alcohol-induced conditioned place preference was detected in control but not MOR KO mice, indicating that MOR is essential for alcohol reward and again, Dlx-MOR KO recapitulated the MOR ...Continue Reading

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Citations

Apr 21, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·L J BoulosB L Kieffer
Jan 11, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jérémie NeastaSami Ben Hamida
Jul 21, 2020·Addiction Biology·Kaitlin C ReevesBrady K Atwood
May 27, 2020·Neuroscience Bulletin·Xin-Yan ZhangYan-Gang Sun
Jun 24, 2018·Nature Reviews. Neuroscience·Emmanuel Darcq, Brigitte Lina Kieffer
Apr 20, 2018·The Journal of Pharmacology and Experimental Therapeutics·Yan Zhou, Mary Jeanne Kreek
Mar 11, 2020·Frontiers in Neuroanatomy·Mageswary SivalingamIshwar S Parhar
Jan 16, 2021·Pharmacogenomics·Mongi Benjeddou, Ana M Peiró
Sep 4, 2021·Neurotoxicology· SushmaSrikanta Kumar Rath

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