Journal
BRAIN STRUCTURE & FUNCTION
Volume 220, Issue 2, Pages 677-702Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00429-014-0717-9
Keywords
Mouse mu opioid receptor; Mouse delta opioid receptor; Receptor brain atlas; Heteromer; Aversive stimuli
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Funding
- Centre National de la Recherche Scientifique
- Institut National de la Sante et de la Recherche Medicale
- Universite de Strasbourg
- Agence Nationale pour la Recherche (IMOP)
- National Institutes of Health [NIDA DA-05010]
- Stefan and Shirley Hatos Center for Neuropharmacology
- region Alsace fellowship
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Opioid receptors are G protein-coupled receptors (GPCRs) that modulate brain function at all levels of neural integration, including autonomic, sensory, emotional and cognitive processing. Mu (MOR) and delta (DOR) opioid receptors functionally interact in vivo, but whether interactions occur at circuitry, cellular or molecular levels remains unsolved. To challenge the hypothesis of MOR/DOR heteromerization in the brain, we generated redMOR/greenDOR double knock-in mice and report dual receptor mapping throughout the nervous system. Data are organized as an interactive database offering an opioid receptor atlas with concomitant MOR/DOR visualization at subcellular resolution, accessible online. We also provide co-immunoprecipitation-based evidence for receptor heteromerization in these mice. In the forebrain, MOR and DOR are mainly detected in separate neurons, suggesting system-level interactions in high-order processing. In contrast, neuronal co-localization is detected in subcortical networks essential for survival involved in eating and sexual behaviors or perception and response to aversive stimuli. In addition, potential MOR/DOR intracellular interactions within the nociceptive pathway offer novel therapeutic perspectives.
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