PMID- 31348890
OWN - NLM
STAT- MEDLINE
DCOM- 20200427
LR  - 20231213
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 178
IP  - 3
DP  - 2019 Jul 25
TI  - A Paranigral VTA Nociceptin Circuit that Constrains Motivation for Reward.
PG  - 653-671.e19
LID - S0092-8674(19)30737-8 [pii]
LID - 10.1016/j.cell.2019.06.034 [doi]
AB  - 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(Pnoc) neurons become most active when mice stop seeking 
      natural rewards. Selective pnVTA(Pnoc) neuron ablation, inhibition, and 
      conditional VTA nociceptin receptor (NOPR) deletion increased operant responding, 
      revealing that the pnVTA(Pnoc) nucleus and VTA NOPR signaling are necessary for 
      regulating reward motivation. Additionally, optogenetic and chemogenetic 
      activation of this pnVTA(Pnoc) 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.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Parker, Kyle E
AU  - Parker KE
AD  - Departments of Anesthesiology, Division of Basic Research, Anatomy and 
      Neurobiology, and Washington University Pain Center, Washington University School 
      of Medicine, St. Louis, MO, USA.
FAU - Pedersen, Christian E
AU  - Pedersen CE
AD  - 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.
FAU - Gomez, Adrian M
AU  - Gomez AM
AD  - Departments of Anesthesiology, Division of Basic Research, Anatomy and 
      Neurobiology, and Washington University Pain Center, Washington University School 
      of Medicine, St. Louis, MO, USA.
FAU - Spangler, Skylar M
AU  - Spangler SM
AD  - 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.
FAU - Walicki, Marie C
AU  - Walicki MC
AD  - Departments of Anesthesiology, Division of Basic Research, Anatomy and 
      Neurobiology, and Washington University Pain Center, Washington University School 
      of Medicine, St. Louis, MO, USA.
FAU - Feng, Shelley Y
AU  - Feng SY
AD  - Departments of Anesthesiology, Division of Basic Research, Anatomy and 
      Neurobiology, and Washington University Pain Center, Washington University School 
      of Medicine, St. Louis, MO, USA.
FAU - Stewart, Sarah L
AU  - Stewart SL
AD  - Departments of Anesthesiology, Division of Basic Research, Anatomy and 
      Neurobiology, and Washington University Pain Center, Washington University School 
      of Medicine, St. Louis, MO, USA.
FAU - Otis, James M
AU  - Otis JM
AD  - Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
FAU - Al-Hasani, Ream
AU  - Al-Hasani R
AD  - 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; Center for Clinical 
      Pharmacology, St. Louis College of Pharmacy and Washington University School of 
      Medicine, St. Louis, MO, USA; Division of Biology and Biomedical Sciences, 
      Washington University School of Medicine, St. Louis, MO, USA.
FAU - McCall, Jordan G
AU  - McCall JG
AD  - 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; Center for Clinical 
      Pharmacology, St. Louis College of Pharmacy and Washington University School of 
      Medicine, St. Louis, MO, USA; Division of Biology and Biomedical Sciences, 
      Washington University School of Medicine, St. Louis, MO, USA.
FAU - Sakers, Kristina
AU  - Sakers K
AD  - Department of Genetics, Washington University School of Medicine, St. Louis, MO, 
      USA; Department of Psychiatry, Washington University School of Medicine, St. 
      Louis, MO, USA.
FAU - Bhatti, Dionnet L
AU  - Bhatti DL
AD  - Departments of Anesthesiology, Division of Basic Research, Anatomy and 
      Neurobiology, and Washington University Pain Center, Washington University School 
      of Medicine, St. Louis, MO, USA.
FAU - Copits, Bryan A
AU  - Copits BA
AD  - Departments of Anesthesiology, Division of Basic Research, Anatomy and 
      Neurobiology, and Washington University Pain Center, Washington University School 
      of Medicine, St. Louis, MO, USA.
FAU - Gereau, Robert W
AU  - Gereau RW
AD  - Departments of Anesthesiology, Division of Basic Research, Anatomy and 
      Neurobiology, and Washington University Pain Center, Washington University School 
      of Medicine, St. Louis, MO, USA.
FAU - Jhou, Thomas
AU  - Jhou T
AD  - Department of Neuroscience, Medical University of South Carolina, Charleston, SC, 
      USA.
FAU - Kash, Thomas J
AU  - Kash TJ
AD  - Department of Pharmacology and Bowles Center for Alcohol Studies, School of 
      Medicine, University of North Carolina, Chapel Hill, NC, USA.
FAU - Dougherty, Joseph D
AU  - Dougherty JD
AD  - Department of Genetics, Washington University School of Medicine, St. Louis, MO, 
      USA; Department of Psychiatry, Washington University School of Medicine, St. 
      Louis, MO, USA.
FAU - Stuber, Garret D
AU  - Stuber GD
AD  - 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.
FAU - Bruchas, Michael R
AU  - Bruchas MR
AD  - 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 Biology and 
      Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, 
      USA; Department of Psychiatry, Washington University School of Medicine, St. 
      Louis, MO, USA. Electronic address: mbruchas@uw.edu.
LA  - eng
GR  - R37 DA033396/DA/NIDA NIH HHS/United States
GR  - F32 DA041184/DA/NIDA NIH HHS/United States
GR  - P30 CA091842/CA/NCI NIH HHS/United States
GR  - T32 DA007261/DA/NIDA NIH HHS/United States
GR  - UL1 TR000448/TR/NCATS NIH HHS/United States
GR  - R01 DA038168/DA/NIDA NIH HHS/United States
GR  - R21 DA034929/DA/NIDA NIH HHS/United States
GR  - T32 EB014855/EB/NIBIB NIH HHS/United States
GR  - T32 GM008151/GM/NIGMS NIH HHS/United States
GR  - R00 DA038725/DA/NIDA NIH HHS/United States
GR  - P30 DA048736/DA/NIDA NIH HHS/United States
GR  - U01 MH109133/MH/NIMH NIH HHS/United States
GR  - UL1 TR002345/TR/NCATS NIH HHS/United States
GR  - R37 DA032750/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Opioid Peptides)
RN  - 0 (Protein Precursors)
RN  - 0 (Receptors, Opioid)
RN  - 0 (prepronociceptin)
RN  - 0 (Nociceptin Receptor)
RN  - 0 (Oprl1 protein, mouse)
SB  - IM
CIN - Nat Rev Neurosci. 2019 Oct;20(10):574-575. PMID: 31391547
CIN - Neuron. 2019 Aug 7;103(3):364-366. PMID: 31394061
MH  - Action Potentials
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Motivation/*drug effects
MH  - Neurons/physiology
MH  - Opioid Peptides/*pharmacology
MH  - Patch-Clamp Techniques
MH  - Protein Precursors/genetics
MH  - Receptors, Opioid/agonists/deficiency/genetics
MH  - *Reward
MH  - Ventral Tegmental Area/*metabolism
MH  - Nociceptin Receptor
MH  - Nociceptin
PMC - PMC7001890
MID - NIHMS1533128
OTO - NOTNLM
OT  - NOPR
OT  - motivation
OT  - neuropeptide
OT  - nociceptin
OT  - opioid
OT  - optogenetics
OT  - orphanin FQ
OT  - photometry
OT  - reward
OT  - ventral tegmental area
COIS- Declaration of Interests The authors declare no competing interests.
EDAT- 2019/07/28 06:00
MHDA- 2020/04/28 06:00
PMCR- 2020/07/25
CRDT- 2019/07/27 06:00
PHST- 2018/01/04 00:00 [received]
PHST- 2018/08/16 00:00 [revised]
PHST- 2019/06/25 00:00 [accepted]
PHST- 2019/07/27 06:00 [entrez]
PHST- 2019/07/28 06:00 [pubmed]
PHST- 2020/04/28 06:00 [medline]
PHST- 2020/07/25 00:00 [pmc-release]
AID - S0092-8674(19)30737-8 [pii]
AID - 10.1016/j.cell.2019.06.034 [doi]
PST - ppublish
SO  - Cell. 2019 Jul 25;178(3):653-671.e19. doi: 10.1016/j.cell.2019.06.034.