1.Role of nociceptin/orphanin FQ and nociceptin opioid peptide receptor in depression and antidepressant effects of nociceptin opioid peptide receptor antagonists
Jong Yung PARK ; Suji CHAE ; Chang Seop KIM ; Yoon Jae KIM ; Hyun Joo YI ; Eunjoo HAN ; Youngshin JOO ; Surim HONG ; Jae Won YUN ; Hyojung KIM ; Kyung Ho SHIN
The Korean Journal of Physiology and Pharmacology 2019;23(6):427-448
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.
Amygdala
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Antidepressive Agents
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Brain
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Brain Stem
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Calcium Channels
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Depression
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Habenula
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Models, Animal
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Neurons
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Neuropeptides
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Opioid Peptides
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Receptors, Drug
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Septal Nuclei