Chronic stress is a factor in many psychiatric diseases, such as depression, PTSD and other anxiety disorders. The brain noradrenergic (NE) system is important in arousal and acute stress reactivity, and is implicated in the etiology of stress-related psychiatric disorders. In the previus grant period, we showed that increasing NE transmission acutely in the prefrontal cortex (PFC) of rats facilitates cognitive flexibility on an attentional setshifting test (AST). By contrast, chonic unpredictable stress (CUS) compromised cognitive flexibility.