title: The neuronal circuit between nociceptin/orphanin FQ and hypocretins/orexins coordinately modulates stress-induced analgesia and anxiety-related behavior.
abstract: The neuropeptide nociceptin/orphanin FQ (N/OFQ), acting on its receptors (NOP), modulates a variety of biological functions and neurobehavior including nociception, stress responses, water and food-intake, locomotor activity, and spatial attention. N/OFQ is conventionally regarded as an "antiopiate" peptide in the brain because central administration of N/OFQ attenuates stress-induced analgesia (SIA) and produces anxiolytic effects. However, naloxone-irreversible SIA and anxiolytic action are unlikely to be mediated by the opiate system. Both N/OFQ and NOP receptors are expressed most abundantly in the hypothalamus, where two other neuropeptides, the hypocretins/orexins (Hcrts), are exclusively synthesized in the lateral hypothalamic area. N/OFQ and Hcrt regulate most cellular physiological responses in opposite directions (e.g., ion channel modulation and second messenger coupling), and produce differential modulations for almost all neurobehavior assessed, including sleep/wake, locomotion, and rewarding behaviors. This chapter focuses on recent studies that provide evidence at a neuroanatomical level showing that a local neuronal circuit linking N/OFQ to Hcrt neurons exists. Functionally, N/OFQ depresses Hcrt neuronal activity at the cellular level, and modulates stress responses, especially SIA and anxiety-related behavior in the whole organism. N/OFQ exerts its attenuation of SIA and anxiolytic action on fear-induced anxiety through direct modulation of Hcrt neuronal activity. The information obtained from these studies has provided insights into how interaction between the Hcrt and N/OFQ systems positively and negatively modulates the complex and integrated stress responses.
authors: AfaSci Research Laboratories, Redwood City, California, USA; Department of Anesthesia, Stanford University School of Medicine, Stanford, California, USA. Electronic address: simonxie@afasci.com.
authors: Xinmin Simon
authors: XS
authors: Xie
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D018847:Opioid Peptides / Q000378:metabolism*; D064446:Orexin Receptors / Q000819:agonists* / Q000378:metabolism; D000068797:Orexins; D011957:Receptors, Opioid / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018847:Opioid Peptides; D064446:Orexin Receptors; D000068797:Orexins; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human
keywords: Anxiety; Anxiolytic; Hypocretin/orexin; Neuronal circuit; Nociceptin/orphanin FQ; Stress-induced analgesia