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A Paranigral VTA Nociceptin Circuit that Constrains Motivation for Reward.
Parker, Kyle E; Pedersen, Christian E; Gomez, Adrian M; Spangler, Skylar M; Walicki, Marie C; Feng, Shelley Y; Stewart, Sarah L; Otis, James M; Al-Hasani, Ream; McCall, Jordan G; Sakers, Kristina; Bhatti, Dionnet L; Copits, Bryan A; Gereau, Robert W; Jhou, Thomas; Kash, Thomas J; Dougherty, Joseph D; Stuber, Garret D; Bruchas, Michael R.
Affiliation
  • Parker KE; Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
  • Pedersen CE; 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.
  • Gomez AM; Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
  • Spangler SM; Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA; Neuroscience Program (DBBS), Washington University School of Medicine, St. Louis, MO, USA.
  • Walicki MC; Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
  • Feng SY; Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
  • Stewart SL; Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
  • Otis JM; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
  • Al-Hasani R; 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 Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, MO, USA; Cente
  • McCall JG; 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 Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, MO, USA; Cente
  • Sakers K; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
  • Bhatti DL; Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
  • Copits BA; Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
  • Gereau RW; Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
  • Jhou T; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
  • Kash TJ; Department of Pharmacology and Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • Dougherty JD; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
  • Stuber GD; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA.
  • Bruchas MR; 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
Cell ; 178(3): 653-671.e19, 2019 07 25.
Article in En | MEDLINE | ID: mdl-31348890
ABSTRACT
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 pnVTAPnoc neurons become most active when mice stop seeking natural rewards. Selective pnVTAPnoc neuron ablation, inhibition, and conditional VTA nociceptin receptor (NOPR) deletion increased operant responding, revealing that the pnVTAPnoc nucleus and VTA NOPR signaling are necessary for regulating reward motivation. Additionally, optogenetic and chemogenetic activation of this pnVTAPnoc 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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Reward / Ventral Tegmental Area / Opioid Peptides / Motivation Type of study: Prognostic_studies Limits: Animals Language: En Journal: Cell Year: 2019 Document type: Article Affiliation country: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Reward / Ventral Tegmental Area / Opioid Peptides / Motivation Type of study: Prognostic_studies Limits: Animals Language: En Journal: Cell Year: 2019 Document type: Article Affiliation country: United States