Abstract

The prefrontal cortex (PFC) plays a critical role in mediating executive functions and orchestrating the way in which we think, decide, and behave. Many studies have shown that PFC neurons not only play a major role in mediating behavioral responses to stress but are also sensitive to stress and undergo remodeling following stress exposure. Activation of the hypothalamic-pituitary-adrenal axis as a result of stress initiates a flood of alterations in prefrontal neurotransmitter release. Dopamine (DA) neurotransmission in the PFC is involved in the modulation of stress responsiveness. Compelling results show that stressful events are associated with increased DA concentrations in the medial PFC. Excessive DA-ergic activity in the medial prefrontal cortex following stress has a negative impact on working memory and executive functions in rodents, monkeys, and humans, making them unable to processing information selectively and impairing cognitive function. Therefore, an exact understanding of these mechanisms may provide important insights into the pathophysiology of executive dysfunction and novel treatment avenues. The present review provides a summary of the neuronal circuitry involved in alterations of PFC dopaminergic neurons under conditions of stress, and then addresses the interaction of PFC DA with glucocorticoids leading to impairment of working memory under conditions of stress.