Noradrenergic Regulation of the Medial Prefrontal Cortex Mediates Stress Coping in Postpartum Female Mice

The prevalence of depression in women increases during the postpartum period. We previously reported that subchronic exposure to social stress decreased passive coping in postpartum female mice. This study aimed to investigate whether noradrenaline regulation might regulate coping styles in mice. We first determined whether a different type of stress, subchronic physical stress, decreases passive coping in postpartum females. Postpartum female, virgin female, and male mice were exposed to subchronic restraint stress (restraint stress for 4 h for 5 consecutive days). Subchronic restraint stress decreased passive coping in postpartum females but not in virgin females and males in the forced swim and tail suspension tests. We next examined the neuronal mechanism by which subchronic stress decreases passive coping in postpartum female mice. Neuronal activity and expression of noradrenergic receptors in the medial prefrontal cortex (mPFC) were analyzed using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction, respectively. The mPFC was manipulated using chemogenetics, knockdown, or an α_2A adrenergic receptor (AR) antagonist. Immunohistochemistry revealed that subchronic restraint stress increased glutamatergic neuron activation in the mPFC via forced swim stress and decreased α_2A AR expression in postpartum females. Chemogenetic activation of glutamatergic neurons in the mPFC, knockdown of α_2AAR in the mPFC, and the α_2A AR receptor antagonist atipamezole treatment decreased passive coping in postpartum females. Subchronic restraint stress decreased passive coping in postpartum females by increasing glutamatergic neuron activity in the mPFC through α_2A AR attenuation. The noradrenergic regulation of the mPFC may be a new target for treating postpartum depression.