Comparative effects of stressors on behavioral and neuroimmune responses of fawn-hooded (FH/Wjd) and Wistar rats: Implications for models of depression

Abstract Patients with depression and rodent models of depression show increased cytokines and activated microglia. Fawn Hooded (FH/Wjd) rats have long been used as a model of depression based on their depressive-like behaviors, high basal corticosterone levels and altered serotonergic levels, but little is known about the neuroimmune function in this model. To test whether depressive-like behaviors relate to dysfunction of the neuroimmune system, depressive-like behaviors in the forced swim test (FST) and corticosterone (CORT) response to the swim test were compared in male Fawn Hooded versus Wistar rats, and cytokine levels in plasma and brain and plasma CORT in response to lipopolysaccharide (LPS, an endotoxin that activates the neuroimmune system) or 1 h restraint were measured. Fawn Hooded rats had more depressive-like behaviors in the FST (decreased swim time and increased immobility) and increased overall plasma CORT compared with Wistar rats. Additionally, Fawn Hooded rats exhibited blunted brain and plasma cytokine response to LPS compared with Wistar rats, an effect that might be related to the blunted plasma CORT response to LPS. No strain differences were found on these measures in response to restraint stress. These results suggest that Fawn Hooded rats have a depressive-like phenotype potentially more closely associated with serotonin dysregulation and a dysregulated HPA axis and remain a relevant model for further defining the role of these systems in depressive conditions.