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

Irene Gallo, Lorenza Rattazzi, Giuseppa Piras, Thomas Gobbetti, Elisabetta Panza, Mauro Perretti, Jeffrey W. Dalley, Fulvio D'Acquisto

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)e114626
JournalPLoS One
Issue number12
Publication statusPublished - 17 Dec 2014


  • Animals
  • Anxiety
  • Corticosterone
  • Exploratory Behavior
  • Gene Deletion
  • Male
  • Mice
  • Molecular Targeted Therapy
  • Nervous System Diseases
  • Oligopeptides
  • Receptors, Formyl Peptide
  • Recognition (Psychology)
  • Signal Transduction
  • Journal Article

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