Formyl peptide receptor as a novel therapeutic target for anxiety-related disorders.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Molecular Targeted Therapy*; Anxiety/*complications ; Anxiety/*drug therapy ; Nervous System Diseases/*complications ; Nervous System Diseases/*drug therapy ; Receptors, Formyl Peptide/*metabolism; Animals ; Anxiety/metabolism ; Anxiety/pathology ; Corticosterone/blood ; Exploratory Behavior/drug effects ; Gene Deletion ; Male ; Mice ; Oligopeptides/pharmacology ; Oligopeptides/therapeutic use ; Receptors, Formyl Peptide/antagonists & inhibitors ; Receptors, Formyl Peptide/deficiency ; Receptors, Formyl Peptide/genetics ; Recognition, Psychology/drug effects ; Signal Transduction/drug effects

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.

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0 (Oligopeptides)
0 (Receptors, Formyl Peptide)
66556-73-8 (butyloxycarbonyl-phenylalanyl-leucyl-phenylalanyl-leucyl-phenylalanine)
W980KJ009P (Corticosterone)

Date Created: 20141218 Date Completed: 20150930 Latest Revision: 20191210

20221213

PMC4269406

10.1371/journal.pone.0114626

25517119