Correction of medial prefrontal cortex and adrenal gland left/right imbalance by deep brain stimulation for depression in rats

Hemispheric brain asymmetries are related to stress coping in both humans and rodents, and imbalanced neural activity between the left and right medial prefrontal cortexes (mPFCs) is observed in depression disorders. Brain stimulation of the PFC is effective to cure depression symptoms. We therefore hypothesized that the imbalanced activity of the mPFCs as well as depression-like behaviors can be induced by chronic stress in rats, and that deep brain stimulation (DBS) can treat such behavior by correcting the asymmetrical activity of the brain regions. Our results indeed show that chronic stress exposure by social isolation (SI) causes depression-like behavior and left/right mPFC activity changes. SI suppressed the activity of both the prelimbic and the infralimbic cortex; however, the extent of the suppression in these regions was oppositely asymmetric. Two weeks of DBS recovered the depression-like behavior and corrected the imbalanced brain activity. In addition, original weight differences between the left and right adrenal glands (AGs) were decreased by SI and recovered by DBS. The integrated index obtained from the mPFCs and AGs asymmetry scores could be useful for estimating the degree of depression. In conclusion, DBS can recover depression-like behavior accompanied by correcting imbalances in both the mPFCs and the AGs.