title: Reduced fear memory and anxiety-like behavior in mice lacking formylpeptide receptor 1.
abstract: N-formylpeptide receptor 1 (FPR1) is a G protein-coupled receptor that mediates pro-inflammatory chemotactic responses by phagocytic leukocytes to N-formylpeptides produced by bacteria or mitochondria. Mice lacking Fpr1 (Fpr1 (-/-) mice) have increased susceptibility to challenge with certain bacteria. FPR1 is also a receptor for annexin-1, which mediates the anti-inflammatory effects of glucocorticoids as well as negative feedback by glucocorticoids of the hypothalamic-pituitary-adrenocortical axis. However, homeostatic functions of FPR1 in the neuroendocrine system have not previously been defined. Here we show that in systematic behavioral testing Fpr1 (-/-) mice exhibited increased exploratory activity, reduced anxiety-like behavior, and impaired fear memory, but normal spatial memory and learning capacity. Consistent with this, the homeostatic serum level of corticosterone in Fpr1 (-/-) mice was significantly lower compared with wild-type mice. The data implicate Fpr1 in modulation of anxiety-like behavior and fear memory by regulating glucocorticoid production.
authors.affiliation: Molecular Signalling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N107, NIH, Bethesda, MD 20892, USA. jgao@niaid.nih.gov
authors.forename: Ji-Liang
authors.initials: JL
authors.lastname: Gao
authors.forename: Erich H
authors.initials: EH
authors.lastname: Schneider
authors.forename: Eugene L
authors.initials: EL
authors.lastname: Dimitrov
authors.forename: Forrest
authors.initials: F
authors.lastname: Haun
authors.forename: Therese M
authors.initials: TM
authors.lastname: Pham
authors.forename: Abdul H
authors.initials: AH
authors.lastname: Mohammed
authors.forename: Ted B
authors.initials: TB
authors.lastname: Usdin
authors.forename: Philip M
authors.initials: PM
authors.lastname: Murphy
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005239:Fear; D005938:Glucocorticoids / Q000378:metabolism; D006706:Homeostasis; D007249:Inflammation; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000235:genetics*
chemical_list: D000305:Adrenal Cortex Hormones; C469988:Fpr1 protein, mouse; D005938:Glucocorticoids; D044042:Receptors, Formyl Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine