Insulin-like growth factor 2 mitigates depressive behavior in a rat model of chronic stress

Depression is a common psychiatric disorder associated with chronic stress. Insulin-like growth factor 2 (IGF2) is a growth factor that serves important roles in the brain during development and at adulthood. Here, the role of IGF2 expression in the hippocampus was investigated in a rat model of depression. A chronic restraint stress (CRS) model of depression was established in rats, exhibiting depression-like behavior as assessed with the sucrose preference test (SPT) and forced swimming test (FST), and with evaluation of the corticosterone levels. Hippocampal IGF2 levels were significantly lower in rats suffering CRS than in controls, as were levels of pERK1/2 and GluR1. Lentivirus-mediated hippocampal IGF2 overexpression alleviated depressive behavior in restrained rats, elevated the levels of pERK1/2 and GluR1 proteins, but it did not affect the expression of pGSK3β, GluR2, NMDAR1, and NMDAR2A. These results suggest the chronic restraint stress induces depressive behavior, which may be mediated by ERK-dependent IGF2 signaling, pointing to an antidepressant role for this molecular pathway. •Chronic restraint stress was associated with decreased IGF2 expression in the hippocampus.•Induced IGF2 expression alleviated depressive-like behaviors in stressed rats.•Induced IGF2 expression prevented GluR1 down-regulation in stressed rats.•The antidepressant effect of IGF2 was mediated by ERK signaling.