Corticotropin-releasing factor receptor type 2-deficient mice display impaired coping behaviors during stress

Two cognate receptors (CRF₁ and CRF₂) mediate the actions of the stress-regulatory corticotropin-releasing factor (CRF) family of peptides. Defining the respective roles of these receptors in the central nervous system is critical in understanding stress neural circuitry and the development of psychiatric disorders. Here, we examined the role of CRF ₂ in several paradigms that assess coping responses to stress. We report that CRF₂ knockout mice responded to a novel setting with increased aggressive behavior toward a bulbectomized conspecific male and show increased immobility during acute swim stress compared with wild-type mice. In addition, CRF₂-deficient mice exhibited impaired adaptation to isolation stress as evinced by prolonged hypophagia and associated weight loss. Collectively, these results point toward a role for CRF₂ pathways in neural circuits that subserve stress-coping behaviors.