Role of nociceptin/orphanin FQ and nociceptin opioid peptide receptor in depression and antidepressant effects of nociceptin opioid peptide receptor antagonists

• Published in: The Korean journal of physiology & pharmacology Vol. 23; no. 6; pp. 427 - 448
• Main Authors: Park, Jong Yung, Chae, Suji, Kim, Chang Seop, Kim, Yoon Jae, Yi, Hyun Joo, Han, Eunjoo, Joo, Youngshin, Hong, Surim, Yun, Jae Won, Kim, Hyojung, Shin, Kyung Ho
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Physiological Society and The Korean Society of Pharmacology 01.11.2019; 대한약리학회
• Subjects: Review; 약리학; Depression; Neuropeptide; Antidepressive agents; Receptors, drug
• ISSN: 1226-4512; 2093-3827
• DOI: 10.4196/kjpp.2019.23.6.427

Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying K channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants.