<p>Nociceptin/orphanin FQ (N/OFQ), an endogenous opioid neuropeptide, and its G-protein coupled receptor NOPR have been implicated in motivation, feeding behaviors, and aversion. Stress-induced dysfunction in these states is central to the development of numerous psychiatric disorders, and the N/OFQ-NOPR system’s role in reward- and stress-related responses has driven broad interest in NOPR as a therapeutic target for anxiety and depression. However, the impact of stress on N/OFQ signaling in the context of its influence on discrete midbrain reward circuitry remains unknown. To this end, we focused on a possible candidate population of N/OFQ neurons in the paranigral ventral tegmental area (pnVTA<sup>PNOC</sup>) that have been shown to act locally on NOPR-containing VTA dopamine neurons to suppress motivation. Here we report and characterize pnVTA<sup>PNOC</sup> sensitivity during exposure to a diverse range of stressors. Our results indicate that pnVTA<sup>PNOC</sup> neurons become recruited during exposure to a variety of acute stressor types, suggesting that this N/OFQ population in the pnVTA could act as a critical bridge between stress and motivation.</p>

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Identification of a stress-sensitive endogenous opioid-containing neuronal population in the paranigral ventral tegmental area

  • Carrie Stine,
  • Amanda L. Pasqualini,
  • Ananya S. Achanta,
  • Joseph C. Johnson,
  • Sanjana Jadhav,
  • David J. Marcus,
  • Michael R. Bruchas

摘要

Nociceptin/orphanin FQ (N/OFQ), an endogenous opioid neuropeptide, and its G-protein coupled receptor NOPR have been implicated in motivation, feeding behaviors, and aversion. Stress-induced dysfunction in these states is central to the development of numerous psychiatric disorders, and the N/OFQ-NOPR system’s role in reward- and stress-related responses has driven broad interest in NOPR as a therapeutic target for anxiety and depression. However, the impact of stress on N/OFQ signaling in the context of its influence on discrete midbrain reward circuitry remains unknown. To this end, we focused on a possible candidate population of N/OFQ neurons in the paranigral ventral tegmental area (pnVTAPNOC) that have been shown to act locally on NOPR-containing VTA dopamine neurons to suppress motivation. Here we report and characterize pnVTAPNOC sensitivity during exposure to a diverse range of stressors. Our results indicate that pnVTAPNOC neurons become recruited during exposure to a variety of acute stressor types, suggesting that this N/OFQ population in the pnVTA could act as a critical bridge between stress and motivation.