title: Blockade of nociceptin/orphanin FQ receptor signaling reverses LPS-induced depressive-like behavior in mice.
abstract: Nociceptin/orphanin FQ is the natural ligand of a Gi-protein coupled receptor named NOP. This peptidergic system is involved in the regulation of mood states and inflammatory responses. The present study aimed to investigate the consequences of blocking NOP signaling in lipopolysaccharide (LPS)-induced sickness and depressive-like behaviors in mice. LPS 0.8mg/kg, ip, significantly induced sickness signs such as weight loss, decrease of water and food intake and depressive-like behavior in the tail suspension test. Nortriptyline (ip, 60min prior the test) reversed the LPS-induced depressive states. The NOP receptor antagonist SB-612111, 30min prior LPS, did not modify LPS-induced sickness signs and depressive-like behavior. However, when injected 24h after LPS, NOP antagonists (UFP-101, icv, and SB-612111, ip) significantly reversed the mood effects of LPS. LPS evoked similar sickness signs and significantly increased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) plasma levels 6h post-injection in wild-type ((NOP(+/+)) and NOP knockout ((NOP(-/-)) mice. However, LPS treatment elicited depressive-like effects in NOP(+/+) but not in NOP(-/-) mice. In conclusion, the pharmacological and genetic blockade of NOP signaling does not affect LPS evoked sickness signs while reversing depressive-like behavior.
authors.affiliation: Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil; Department of Medical Science, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.
authors.forename: Iris U
authors.initials: IU
authors.lastname: Medeiros
authors.affiliation: Department of Medical Science, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ruzza
authors.affiliation: Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Laila
authors.initials: L
authors.lastname: Asth
authors.affiliation: Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Pedro R T
authors.initials: PR
authors.lastname: Romão
authors.affiliation: Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil. Electronic address: egavioli@hotmail.com.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Gavioli
authors.affiliation: Department of Medical Science, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calo
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000094942:Nociceptin Receptor
chemical_list: D000928:Antidepressive Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011957:Receptors, Opioid; D014409:Tumor Necrosis Factor-alpha; D000094942:Nociceptin Receptor; C000722287:Oprl1 protein, mouse
keywords: Depression; Inflammation; Lipopolysaccharide-induced depressive; NOP receptor; Nociceptin/orphanin FQ; Tail suspension test