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

TL;DR

The study identifies a group of neurons in the brain that respond to stress and may link stress to changes in motivation.

Contribution

The novel finding is the characterization of a stress-sensitive N/OFQ-containing neuronal population in the pnVTA and its potential role in stress-motivation interactions.

Findings

pnVTAPNOC neurons are activated by various acute stressors.

These neurons may serve as a bridge between stress and motivation.

The N/OFQ-NOPR system in the pnVTA could influence midbrain reward circuitry.

Abstract

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.

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