Korean J Physiol Pharmacol.  2019 Nov;23(6):427-448. 10.4196/kjpp.2019.23.6.427.

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

• Park JY
• Chae S
• Kim CS
• Kim YJ
• Yi HJ
• Han E
• Joo Y
• Hong S
• Yun JW
• Kim H
• Shin KH

• KMID: 2461036
• DOI: http://doi.org/10.4196/kjpp.2019.23.6.427

Abstract

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.

Keyword

Antidepressive agents; Depression; Neuropeptide; Receptors, drug

MeSH Terms

Amygdala
Antidepressive Agents
Brain
Brain Stem
Calcium Channels
Depression*
Habenula
Models, Animal
Neurons
Neuropeptides
Opioid Peptides*
Receptors, Drug
Septal Nuclei
Antidepressive Agents
Calcium Channels
Neuropeptides
Opioid Peptides
Receptors, Drug