دورية أكاديمية
Mu opioid receptors in GABAergic neurons of the forebrain promote alcohol reward and drinking.
العنوان: | Mu opioid receptors in GABAergic neurons of the forebrain promote alcohol reward and drinking. |
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المؤلفون: | Ben Hamida S; Département de Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U-964, CNRS UMR-7104, Université de Strasbourg, France.; Douglas Research Center, Department of Psychiatry, Faculty of Medicine, McGill University, Canada., Boulos LJ; Département de Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U-964, CNRS UMR-7104, Université de Strasbourg, France.; Douglas Research Center, Department of Psychiatry, Faculty of Medicine, McGill University, Canada., McNicholas M; Douglas Research Center, Department of Psychiatry, Faculty of Medicine, McGill University, Canada., Charbogne P; Douglas Research Center, Department of Psychiatry, Faculty of Medicine, McGill University, Canada.; Current position: Department of Neuroscience, School of Medicine, Brain Science Institute, Johns Hopkins University, Baltimore, MD, USA., Kieffer BL; Département de Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U-964, CNRS UMR-7104, Université de Strasbourg, France.; Douglas Research Center, Department of Psychiatry, Faculty of Medicine, McGill University, Canada. |
المصدر: | Addiction biology [Addict Biol] 2019 Jan; Vol. 24 (1), pp. 28-39. Date of Electronic Publication: 2017 Nov 02. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 9604935 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1369-1600 (Electronic) Linking ISSN: 13556215 NLM ISO Abbreviation: Addict Biol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Hoboken, NJ : Wiley-Blackwell Original Publication: Abingdon, Oxfordshire, UK ; Cambridge, MA : Carfax, c1996- |
مواضيع طبية MeSH: | Reward*, Alcohol Drinking/*genetics , Central Nervous System Depressants/*administration & dosage , Ethanol/*administration & dosage , GABAergic Neurons/*metabolism , Neostriatum/*metabolism , Receptors, Opioid, mu/*genetics , Ventral Tegmental Area/*metabolism, Alcohol Drinking/metabolism ; Animals ; Behavior, Animal ; Mesencephalon/metabolism ; Mice ; Mice, Knockout ; Prosencephalon/metabolism ; Rhombencephalon/metabolism ; Self Administration |
مستخلص: | 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 KO phenotype. Taste preference and blood alcohol levels were otherwise unchanged in mutant lines. Together, our data demonstrate that MOR expressed in forebrain GABAergic neurons is essential for alcohol reward-driven behaviors, including drinking and place conditioning. Challenging the prevailing VTA-centric hypothesis, this study reveals another mechanism of MOR-mediated alcohol reward and consumption, which does not necessarily require local VTA MORs but rather engages striatal MOR-dependent mechanisms. (© 2017 Society for the Study of Addiction.) |
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معلومات مُعتمدة: | International Institut National de la Santé et de la Recherche Médicale (INSERM); P50 DA005010 United States DA NIDA NIH HHS; International Centre National de la Recherche Scientifique (CNRS); NIAAA #16658 United States NH NIH HHS; International Université de Strasbourg; International Canada Research Chairs; NIDA # 005010 United States NH NIH HHS; U01 AA016658 United States AA NIAAA NIH HHS |
فهرسة مساهمة: | Keywords: alcohol intake; forebrain GABAergic neurons; mu opioid receptor |
المشرفين على المادة: | 0 (Central Nervous System Depressants) 0 (Oprm protein, mouse) 0 (Receptors, Opioid, mu) 3K9958V90M (Ethanol) |
تواريخ الأحداث: | Date Created: 20171103 Date Completed: 20200402 Latest Revision: 20231112 |
رمز التحديث: | 20231112 |
مُعرف محوري في PubMed: | PMC5932272 |
DOI: | 10.1111/adb.12576 |
PMID: | 29094432 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1369-1600 |
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DOI: | 10.1111/adb.12576 |