Stress Reduces Extracellular ATP in the Prefrontal Cortex and Activates the Prefrontal Cortex–Lateral Habenula Pathway for Depressive-like Behavior

Major depressive disorder (MDD) is a common and devastating mental disorder that causes feelings of sadness and anhedonia (loss of pleasure or interest in activities), lack of motivation, cognitive deficits, and vegetative symptoms. It is the leading cause of disability around the world, affecting 4.4% of world’s population. Although the etiology of MDD remains unclear, recent research has begun to unravel its pathophysiological mechanisms. Arguably, three brain regions stand out as most involved in MDD—the prefrontal cortex (PFC), the hippocampus, and the amygdala—of which the PFC seems to be most consistently impaired in MDD (1).