Nociceptin/orphanin FQ neurons in the Arcuate Nucleus and Ventral Tegmental Area Act via Nociceptin Opioid Peptide Receptor Signaling to Inhibit Proopiomelanocortin and A10 Dopamine Neurons and Thereby Modulate Ingestion of Palatable Food

摘要: The neuropeptide nociceptin/orphanin FQ (N/OFQ) inhibits neuronal activity via its cognate nociceptin opioid peptide (NOP) receptor throughout the peripheral and central nervous systems, including those areas involved in homeostatic hedonic regulation of energy homeostasis. We thus tested hypothesis that N/OFQ neurons hypothalamic arcuate nucleus (ARC) ventral tegmental area (VTA) act NOP signaling to inhibit nearby anorexigenic proopiomelanocortin (POMC) A10 dopamine excitability, respectively, thereby modulate ingestion palatable food. Electrophysiologic recordings were performed slices prepared from transgenic male ovariectomized (OVX) female N/OFQ-cre/enhanced green fluorescent protein-POMC, N/OFQ-cre tyrosine hydroxylase-cre animals see if optogenetically-stimulated release could directly these populations. Binge-feeding behavioral experiments also conducted where exposed a high-fat-diet (HFD) for one hour each day five days monitored intake. Photostimulation ARC VTA produces an outward current POMC receiving input cells. This is associated with hyperpolarization decreased firing. These features are sex hormone- diet-dependent; estradiol-treated OVX females being less sensitive, obese males more N/OFQ. Limited access HFD causes dramatic escalation consumption, such eat 25-45% their daily intake during one-hour exposure. Moreover, receptor-mediated balance circuits engaged, as injected into or respectively diminishes potentiates this binge-like increase manner heightened by diet-induced obesity dampened estradiol females. Collectively, findings provide key support idea regulates appetitive behavior sex-, site- diet-specific ways, along important insights aberrant patterns feeding pertinent pathogenesis food addiction.