title: Nociceptin/orphanin FQ receptor antagonists as innovative antidepressant drugs.
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.affiliation: Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, 59078-970 Natal-RN, Brazil. Electronic address: egavioli@hotmail.com.
authors.forename: Elaine Cristina
authors.initials: EC
authors.lastname: Gavioli
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calo'
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001007:Anxiety / Q000378:metabolism; D006801:Humans; D019964:Mood Disorders / Q000378:metabolism; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology; D013315:Stress, Psychological / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D000928:Antidepressive Agents; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human
keywords: 5-HT; 5-HT neurotransmission; ACTH; Accumbens nucleus; Amy; BDNF; CRF; DRN; HPA; Hipp; LC; MAPK; Mood disorders; N/OFQ; NAc; NOP antagonists; NOP receptor; NTS; Nociceptin/orphanin FQ; PFC; POMC; Stress; VTA; adrenocorticotropic hormone; amygdala; brain derived neurotrophic factor; corticotropin release factor; dorsal raphe nucleus; hippocampus; hypothalamus–pituitary–adrenal axis; locus ceruleus; mitogen-activated protein kinase; nociceptin/orphanin FQ; nociceptin/orphanin FQ peptide receptor; nucleus of the solitary tract; ppN/OFQ; prefrontal cortex; prepronociceptin/orphanin FQ; proopiomelanocortin; serotonin; ventral tegmental area