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Nociceptin/orphanin FQ receptor antagonists as innovative antidepressant drugs.
Pharmacol Ther 2013; 140(1):10-25P&T

Abstract

Nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) were identified in the mid 90s as a novel peptidergic system structurally related to opioids. A growing body of preclinical evidence suggests that blockade of NOP receptors evokes antidepressant-like actions. These have been explored using a range of compounds (peptide and non peptide antagonists), across different species (rat and mouse) and assays (behavioral despair and chronic mild stress) suggesting a robust and consistent antidepressant-like effect. Moreover, rats and mice knockout for the NOP receptor gene display an antidepressant-like phenotype in behavioral despair assays. Electrophysiological, immunohistochemical and neurochemical studies point to an important role played by monoaminergic systems, particularly 5-HTergic, in mediating the antidepressant-like properties of NOP antagonists. However other putative mechanisms of action, including modulation of the CRF system, circadian rhythm and a possible neuroendocrine-immune control might be involved. A close relationship between the N/OFQ-NOP receptor system and stress responses is well described in the literature. Stressful situations also alter endocrine, behavioral and neurochemical parameters in rats and chronic administration of a NOP antagonist restored these alterations. Interestingly, clinical findings showed that plasma N/OFQ levels were significantly altered in major and post-partum depression, and bipolar disease patients. Collectively, data in the literature support the notion that blockade of NOP receptor signaling could be a novel and interesting strategy for the development of innovative antidepressants.

Authors+Show Affiliations

Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, 59078-970 Natal-RN, Brazil. Electronic address: egavioli@hotmail.com.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23711793

Citation

Gavioli, Elaine Cristina, and Girolamo Calo'. "Nociceptin/orphanin FQ Receptor Antagonists as Innovative Antidepressant Drugs." Pharmacology & Therapeutics, vol. 140, no. 1, 2013, pp. 10-25.
Gavioli EC, Calo' G. Nociceptin/orphanin FQ receptor antagonists as innovative antidepressant drugs. Pharmacol Ther. 2013;140(1):10-25.
Gavioli, E. C., & Calo', G. (2013). Nociceptin/orphanin FQ receptor antagonists as innovative antidepressant drugs. Pharmacology & Therapeutics, 140(1), pp. 10-25. doi:10.1016/j.pharmthera.2013.05.008.
Gavioli EC, Calo' G. Nociceptin/orphanin FQ Receptor Antagonists as Innovative Antidepressant Drugs. Pharmacol Ther. 2013;140(1):10-25. PubMed PMID: 23711793.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nociceptin/orphanin FQ receptor antagonists as innovative antidepressant drugs. AU - Gavioli,Elaine Cristina, AU - Calo',Girolamo, Y1 - 2013/05/24/ PY - 2013/05/06/received PY - 2013/05/07/accepted PY - 2013/5/29/entrez PY - 2013/5/29/pubmed PY - 2014/4/8/medline KW - 5-HT KW - 5-HT neurotransmission KW - ACTH KW - Accumbens nucleus KW - Amy KW - BDNF KW - CRF KW - DRN KW - HPA KW - Hipp KW - LC KW - MAPK KW - Mood disorders KW - N/OFQ KW - NAc KW - NOP antagonists KW - NOP receptor KW - NTS KW - Nociceptin/orphanin FQ KW - PFC KW - POMC KW - Stress KW - VTA KW - adrenocorticotropic hormone KW - amygdala KW - brain derived neurotrophic factor KW - corticotropin release factor KW - dorsal raphe nucleus KW - hippocampus KW - hypothalamus–pituitary–adrenal axis KW - locus ceruleus KW - mitogen-activated protein kinase KW - nociceptin/orphanin FQ KW - nociceptin/orphanin FQ peptide receptor KW - nucleus of the solitary tract KW - ppN/OFQ KW - prefrontal cortex KW - prepronociceptin/orphanin FQ KW - proopiomelanocortin KW - serotonin KW - ventral tegmental area SP - 10 EP - 25 JF - Pharmacology & therapeutics JO - Pharmacol. Ther. VL - 140 IS - 1 N2 - Nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) were identified in the mid 90s as a novel peptidergic system structurally related to opioids. A growing body of preclinical evidence suggests that blockade of NOP receptors evokes antidepressant-like actions. These have been explored using a range of compounds (peptide and non peptide antagonists), across different species (rat and mouse) and assays (behavioral despair and chronic mild stress) suggesting a robust and consistent antidepressant-like effect. Moreover, rats and mice knockout for the NOP receptor gene display an antidepressant-like phenotype in behavioral despair assays. Electrophysiological, immunohistochemical and neurochemical studies point to an important role played by monoaminergic systems, particularly 5-HTergic, in mediating the antidepressant-like properties of NOP antagonists. However other putative mechanisms of action, including modulation of the CRF system, circadian rhythm and a possible neuroendocrine-immune control might be involved. A close relationship between the N/OFQ-NOP receptor system and stress responses is well described in the literature. Stressful situations also alter endocrine, behavioral and neurochemical parameters in rats and chronic administration of a NOP antagonist restored these alterations. Interestingly, clinical findings showed that plasma N/OFQ levels were significantly altered in major and post-partum depression, and bipolar disease patients. Collectively, data in the literature support the notion that blockade of NOP receptor signaling could be a novel and interesting strategy for the development of innovative antidepressants. SN - 1879-016X UR - https://www.unboundmedicine.com/medline/citation/23711793/Nociceptin/orphanin_FQ_receptor_antagonists_as_innovative_antidepressant_drugs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0163-7258(13)00123-X DB - PRIME DP - Unbound Medicine ER -