Upregulations of?1 adrenergic receptors and noradrenaline synthases in the medial prefrontal cortex are associated with emotional and cognitive dysregulation induced by post-weaning social isolation in male rats

Early-life social isolation induces emotional and cognitive dysregulation, such as increased aggression and anxiety, and decreases neuron excitability in the medial prefrontal cortex (mPFC). The noradrenergic system in the mPFC regulates emotion and cognitive function via alpha 1 or alpha 2A adrenergic receptors, depending on noradrenaline levels. However, social isolation-induced changes in the mPFC noradrenergic system have not been reported. Here, male Wistar rats received post-weaning social isolation for nine consecutive weeks and were administered behavioral tests (novel object recognition, elevated plus maze, aggression, and forced swimming, sequentially). Protein expression levels in the mPFC noradrenergic system (alpha 1 and alpha 2A adrenergic receptors, tyrosine hydroxylase, and dopamine-beta-hydroxylase used as indices of noradrenaline synthesis and release) were examined through western blotting. Social isolation caused cognitive dysfunction, anxiety-like behavior, and aggression, but not behavioral despair. Socially-isolated rats exhibited increased protein levels of the alpha 1 adrenergic receptor, tyrosine hydroxylase, and dopamine-beta-hydroxylase in the mPFC; there was no significant difference between the groups in the alpha 2A adrenergic receptor expression levels. Preferential activation of the alpha 1 adrenergic receptor caused by high noradrenaline concentration in the mPFC may be involved in social isolation-induced emotional and cognitive regulation impairments. Targeting the alpha 1 adrenergic receptor signaling pathway is a potential therapeutic strategy for psychiatric disorders with symptomatic features such as emotional and cognitive dysregulation.