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Reduced fear memory and anxiety-like behavior in mice lacking formylpeptide receptor 1
Ji-Liang Gao1, Erich H Schneider, Eugene L Dimitrov
1Molecular 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
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.
Insights
N-formylpeptide receptor 1 (FPR1) influences neuroendocrine functions. Mice lacking FPR1 show altered anxiety and fear memory, linked to changes in corticosterone levels.
Area of Science:
- Neuroendocrinology
- Immunology
- Behavioral Neuroscience
Background:
- N-formylpeptide receptor 1 (FPR1) is a G protein-coupled receptor involved in inflammatory responses and glucocorticoid signaling.
- Its homeostatic functions within the neuroendocrine system remain largely undefined.
Purpose of the Study:
- To investigate the role of FPR1 in neuroendocrine regulation and behavior.
- To determine the impact of FPR1 deficiency on anxiety-like behavior, fear memory, and corticosterone levels.
Main Methods:
- Systematic behavioral testing of Fpr1 knockout mice (Fpr1 (-/-)) and wild-type littermates.
- Measurement of homeostatic serum corticosterone levels.
Main Results:
- Fpr1 (-/-) mice displayed increased exploratory activity and reduced anxiety-like behavior.
- Fear memory was impaired in Fpr1 (-/-) mice, while spatial memory and learning remained normal.
- Homeostatic serum corticosterone levels were significantly lower in Fpr1 (-/-) mice compared to wild-type controls.
Conclusions:
- FPR1 plays a crucial role in modulating anxiety-like behavior and fear memory.
- These behavioral effects are associated with FPR1's regulation of glucocorticoid production within the neuroendocrine system.
