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

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

doi:10.4196/kjpp.2019.23.6.427

Cited by 11 publications

(7 citation statements)

References 170 publications

(295 reference statements)

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“…Unlike µ- and δ-opioid receptor subtypes, activation of ĸ-opioid and nociceptin opioid peptide (NOP) receptors are generally associated with a decrease in central monoaminergic activity (Gavioli and Calo, 2013; Schlicker and Morari, 2000; Tao and Auerbach, 2005; Yılmaz et al, 2006). It has also been suggested that agonists of ĸ- or NOP-receptors cause negative effects on mood (Ji et al, 2021; Toll et al, 2021), and blocking these receptors causes antidepressant-like effects (Jacobson et al, 2020; Park et al, 2019; Shang et al, 2021). Therefore, further studies are needed to clarify whether the antidepressant-like activity of tofisopam is associated with any attenuation in the functions of ĸ- and NOP-opioidergic receptors.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study

et al. 2022

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Background: Depression is a disease that affects millions of people worldwide, and the discovery and development of effective and safe antidepressant drugs is one of the important topics of psychopharmacology. Objectives: In this study, it was aimed to investigate the antidepressant-like activity potential of tofisopam, an anxiolytic drug with 2,3-benzodiazepine structure, and to elucidate the pharmacological mechanisms mediating this effect. Methods: The antidepressant-like activity of tofisopam was investigated using tail suspension and modified forced swimming tests. Possible interactions of tofisopam with µ- and δ-opioid receptor subtypes were clarified by pharmacological antagonism, molecular docking and molecular dynamics simulation studies. Results: Tofisopam (50 and 100 mg/kg) significantly shortened the immobility time of mice in both the tail suspension and the modified forced swimming tests. The drug, at the same doses, prolonged the duration of swimming and climbing behaviours measured in modified forced swimming tests. A dosage of 25 mg/kg was ineffective. Mechanistic studies showed that the pretreatment with p-chlorophenylalanine methyl ester (serotonin synthesis inhibitor; 4 consecutive days, 100 mg/kg), α-methyl-para-tyrosine methyl ester (catecholamine synthesis inhibitor; 100 mg/kg), naloxonazine (selective µ-opioid receptor blocker, 7 mg/kg) and naltrindole (a selective δ-opioid receptor blocker, 0.99 mg/kg) abolished the anti-immobility effect induced by the 50 mg/kg dose of tofisopam in the tail suspension tests. Our in silico studies supported the behavioural findings that the antidepressant-like effect of tofisopam is mediated by μ- and δ-opioid receptors. Conclusion: This study is the first to show that tofisopam has antidepressant-like activity mediated by the serotonergic, catecholaminergic and opioidergic systems.

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Section: Discussionmentioning

confidence: 99%

Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study

et al. 2022

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“…However, it should be remarked that the expression of NOP receptors in different neuronal ensembles within the same brain regions could lead to the disinhibition of their outputs in response to N/OFQ. Furthermore, given the adaptability of the N/OFQ-NOP receptor system in response to behaviorally relevant experiences, the net effects of its activation/inactivation could also be regulated by state-dependent physiological and pathological factors such as anxiety, mood disorders and drug addiction (for review see [ 57 , 59 ]. Consistently, neuroanatomical data demonstrated a high expression of N/OFQ and NOP receptor in brain regions of the mesocorticolimbic system, the extended amygdala and the hypothalamus, that are known to subserve the regulation of motivated behaviors, stress response and affection [ 17 , 18 , 60 , 61 , 62 ].…”

Section: Neurobiology Of the N/ofq-nop Receptor Systemmentioning

confidence: 99%

“…This effect was specific to the BNST, since intra-CeA N/OFQ microinjections were ineffective [ 127 ]. Although highly speculative, an intriguing explanation is that N/OFQ could promote stress response by silencing the inhibitory signals that the BNST tonically sends to the PVN [ 59 ]. N/OFQ and NOP receptors mRNAs are also enriched in the suprachiasmatic nucleus of the hypothalamus (SCN) [ 128 , 129 ].…”

Section: Neurobiology Of the N/ofq-nop Receptor Systemmentioning

confidence: 99%

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders

Ubaldi

Cannella

Borruto

et al. 2021

IJMS

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Nociceptin/orphanin FQ (N/OFQ) is a 17-residue neuropeptide that binds the nociceptin opioid-like receptor (NOP). N/OFQ exhibits nucleotidic and aminoacidics sequence homology with the precursors of other opioid neuropeptides but it does not activate either MOP, KOP or DOP receptors. Furthermore, opioid neuropeptides do not activate the NOP receptor. Generally, activation of N/OFQ system exerts anti-opioids effects, for instance toward opioid-induced reward and analgesia. The NOP receptor is widely expressed throughout the brain, whereas N/OFQ localization is confined to brain nuclei that are involved in stress response such as amygdala, BNST and hypothalamus. Decades of studies have delineated the biological role of this system demonstrating its involvement in significant physiological processes such as pain, learning and memory, anxiety, depression, feeding, drug and alcohol dependence. This review discusses the role of this peptidergic system in the modulation of stress and stress-associated psychiatric disorders in particular drug addiction, mood, anxiety and food-related associated-disorders. Emerging preclinical evidence suggests that both NOP agonists and antagonists may represent a effective therapeutic approaches for substances use disorder. Moreover, the current literature suggests that NOP antagonists can be useful to treat depression and feeding-related diseases, such as obesity and binge eating behavior, whereas the activation of NOP receptor by agonists could be a promising tool for anxiety.

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“…KNT-127 [121], Rubiscolin-6 [122], and SNC80 [123] are preclinical DOR receptor agonists that decreased depressive-like behaviors in mouse models of depression. N/OFQ is an endogenous opioid peptide that binds to nociceptin receptor (NOPr), part of the opioid receptor family [124]. NOPr antagonists such as LY2940094 [125] and UFP-101 [126] reduced anhedonia and rescued stress-like and anxiety-like behaviors by restoring neurogenesis after chronic stress.…”

Section: Opioid Receptorsmentioning

confidence: 99%

Novel Pharmacological Approaches to the Treatment of Depression

Elias

Zhang

Manners

2022

Life

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Major depressive disorder is one of the most prevalent mental health disorders. Monoamine-based antidepressants were the first drugs developed to treat major depressive disorder. More recently, ketamine and other analogues were introduced as fast-acting antidepressants. Unfortunately, currently available therapeutics are inadequate; lack of efficacy, adverse effects, and risks leave patients with limited treatment options. Efforts are now focused on understanding the etiology of depression and identifying novel targets for pharmacological treatment. In this review, we discuss promising novel pharmacological targets for the treatment of major depressive disorder. Targeting receptors including N-methyl-D-aspartate receptors, peroxisome proliferator-activated receptors, G-protein-coupled receptor 39, metabotropic glutamate receptors, galanin and opioid receptors has potential antidepressant effects. Compounds targeting biological processes: inflammation, the hypothalamic-pituitary-adrenal axis, the cholesterol biosynthesis pathway, and gut microbiota have also shown therapeutic potential. Additionally, natural products including plants, herbs, and fatty acids improved depressive symptoms and behaviors. In this review, a brief history of clinically available antidepressants will be provided, with a primary focus on novel pharmaceutical approaches with promising antidepressant effects in preclinical and clinical studies.

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

Cited by 11 publications

References 170 publications

Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study

Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders

Novel Pharmacological Approaches to the Treatment of Depression

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