title: Formyl peptide receptor as a novel therapeutic target for anxiety-related disorders.
abstract: Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface.
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Irene
authors.initials: I
authors.lastname: Gallo
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Rattazzi
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Piras
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gobbetti
authors.affiliation: Department of Experimental Pharmacology, University of Naples "Federico II", Naples, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Panza
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
authors.affiliation: Department of Psychology, University of Cambridge, Cambridge, United Kingdom; Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Dalley
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Fulvio
authors.initials: F
authors.lastname: D'Acquisto
mesh_terms: D000818:Animals; D001007:Anxiety / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D005106:Exploratory Behavior / Q000187:drug effects; D017353:Gene Deletion; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy; D009422:Nervous System Diseases / Q000150:complications* / Q000188:drug therapy*; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; C033373:butyloxycarbonyl-phenylalanyl-leucyl-phenylalanyl-leucyl-phenylalanine; D003345:Corticosterone