Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder.

This review focuses on the role of norepinephrine (NE) in traumatic stress. The review is divided into three sections. The first section, "Norepinephrine and Arousal," describes preclinical studies related to norepinephrine's role in arousal, orienting to novel stimuli, selective attention and vigilance. It also contains a brief discussion of NE and its relationship to fear-provoking stimuli followed by preclinical and clinical studies that demonstrate heightened noradrenergic neuronal reactivity, increased alpha 2 receptor sensitivity and exaggerated arousal in organisms that have been exposed to chronic uncontrollable stress. The second section, "Norepinephrine and Memory," describes preclinical and clinical studies related to norepinephrine's role in enhanced encoding of memory for arousing and aversive events and in subsequent re-experiencing symptoms such as, intrusive memories and nightmares. The third section, "Norepinephrine and Pharmacologic Treatment," briefly discusses the use of adrenergic blockers, clonidine and propranol, as well as tricyclic and MAO inhibitors, for the treatment of PTSD. Finally, we attempt to synthesize trauma-related preclinical and clinical studies of norepinephrine. We do this, in part, by focusing on a series of yohimbine studies in subjects with PTSD because data from these studies allow for a discussion that brings together preclinical and clinical findings relevant to trauma-related alterations in arousal and memory.