The antidepressant-like effect of resolvin E1 in repeated prednisolone-induced depression model mice

Resolvin E1 (RvE1) is an anti-inflammatory lipid mediator derived from eicosapentaenoic acid. We previously demonstrated that intracerebroventricular (i.c.v.) and intra-medial prefrontal cortex (mPFC) infusions of RvE1 produce antidepressant-like effects in a lipopolysaccharide-induced depression mouse model. To further confirm the antidepressant-like effect of RvE1, the present study examined whether RvE1 ameliorated depression-like behavior induced by repeated injections of prednisolone (PSL), a synthetic glucocorticoid, in male ICR mice. We first ascertained whether repeated subcutaneous treatment with PSL (50 mg/kg, once a day) affected locomotor activity and anxiety-like behavior in the open field test (OFT; after a 5-day PSL treatment) and induced depression-like behavior in the tail suspension test (TST; after a 6-day PSL treatment) and forced swim test (FST; after a 7-day PSL treatment). Repeated PSL injections significantly increased immobility in the FST, which was not ameliorated by acute desipramine treatment (30 mg/kg, i.p.), but not in the TST, without affecting locomotor activity and anxiety-like behavior in the OFT. Subsequently, we investigated the therapeutic effects of i.c.v. (1 ng) and intra-mPFC (50 pg/side) infusions of RvE1 in the repeated PSL-induced depression mouse model using the OFT and FST after 5- and 6-day PSL treatments, respectively. The repeated PSL-induced increase in immobility in the FST was significantly attenuated by both i.c.v. and intra-mPFC infusions of RvE1 without affecting the locomotor activity and anxiety-like behavior. In addition, a single i.c.v. infusion of RvE1 immediately before the first or fourth injection of PSL also attenuated PSL-induced depression-like behavior in the FST, suggesting the preventive effect of RvE1. These results indicate that RvE1 produces antidepressant-like effects in a mouse model of repeated PSL-induced depression.