Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

• DOI: 10.1371/journal.pone.0114626
• Publication Date: 2014-12-18T05:34:52Z
• Authors: Irene Gallo; Lorenza Rattazzi; Giuseppa Piras; Thomas Gobbetti; Elisabetta Panza; Mauro Perretti; Jeffrey W. Dalley; Fulvio D'Acquisto
• Keywords: Male; 0301 basic medicine; Science; Q; R; Recognition, Psychology; Anxiety; Receptors, Formyl Peptide; 3. Good health; Mice; 03 medical and health sciences; Exploratory Behavior; Medicine; Animals; Molecular Targeted Therapy; Nervous System Diseases; Corticosterone; Oligopeptides; Gene Deletion; Research Article; Signal Transduction

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.