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Nociceptin and its receptor are widely distributed throughout the brain in regions associated with reward behavior, yet how and when they act is unknown. Here, we dissected the role of a nociceptin peptide circuit in reward seeking. We generated a prepronociceptin (Pnoc)-Cre mouse line that revealed a unique subpopulation of paranigral ventral tegmental area (pnVTA) neurons enriched in prepronociceptin. Fiber photometry recordings during progressive ratio operant behavior revealed pnVTA neurons become most active when mice stop seeking natural rewards. Selective pnVTA neuron ablation, inhibition, and conditional VTA nociceptin receptor (NOPR) deletion increased operant responding, revealing that the pnVTA nucleus and VTA NOPR signaling are necessary for regulating reward motivation. Additionally, optogenetic and chemogenetic activation of this pnVTA nucleus caused avoidance and decreased motivation for rewards. These findings provide insight into neuromodulatory circuits that regulate motivated behaviors through identification of a previously unknown neuropeptide-containing pnVTA nucleus that limits motivation for rewards.
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http://dx.doi.org/10.1016/j.cell.2019.06.034 | DOI Listing |
J Neurosci
July 2025
Departments of Neuroscience, Northwestern University, Chicago, Illinois 60611
Opioid abuse poses a major healthcare challenge. To meet this challenge, the brain mechanisms underlying opioid abuse need to be more systematically characterized. It is commonly thought that the addictive potential of opioids stems from their ability to enhance the activity of ventral tegmental area (VTA) dopaminergic neurons.
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July 2019
Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA; Division of Bi