Here, we generated an animal model of PPD in which the effects of chronic unpredictable stress on depressive behaviors of postpartum female mice were tested. Additionally, Bdnf and Bdnf-specific exon mRNA expression in the medial PFC (mPFC) were evaluated and the correlation between depressive behaviors and BDNF expresson levels were analyzed. Next, we measured the susceptibility of postpartum mice to the subthreshold stress. We also analyzed the FoxO1 mRNA and protein expression and its correlation with depressive behaviors. Finally, we generated mice with conditional BDNF deletion in the mPFC and determined the impact of BDNF loss on depression-related behaviors and FoxO1 expression in mPFC.