A Paranigral VTA Nociceptin Circuit that Constrains Motivation for Reward.

Cell

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

Published: July 2019


Article Synopsis

  • Researchers investigated the role of nociceptin and its receptor in the brain's reward-seeking behavior.
  • They created a mouse model to identify specific neurons in the paranigral ventral tegmental area (pnVTA) that are activated when animals stop pursuing rewards.
  • The study found that these pnVTA neurons and nociceptin receptor signaling are crucial for controlling motivation for rewards, and manipulating these neurons can either increase motivation or lead to avoidance of rewards.

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Article 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 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001890PMC
http://dx.doi.org/10.1016/j.cell.2019.06.034DOI Listing

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A Paranigral VTA Nociceptin Circuit that Constrains Motivation for Reward.

Cell

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

Article Synopsis
  • Researchers investigated the role of nociceptin and its receptor in the brain's reward-seeking behavior.
  • They created a mouse model to identify specific neurons in the paranigral ventral tegmental area (pnVTA) that are activated when animals stop pursuing rewards.
  • The study found that these pnVTA neurons and nociceptin receptor signaling are crucial for controlling motivation for rewards, and manipulating these neurons can either increase motivation or lead to avoidance of rewards.
View Article and Find Full Text PDF