Increased cerebrospinal fluid (CSF) levels of CRH have been linked to PTSD by several studies.47-48 Psychobiological

resilience may be related to an ability to restrain the initial CRH response to acute stress. Too few investigations have been conducted in other anxiety disorder patient groups to form definitive conclusions regarding the pathophysiological role of CRH. LC-NE system Activation of the LC results in increased release of NE in LC projection regions, such as the amygdala, PFC, and the hippocampus. The LC is activated Inhibitors,research,lifescience,medical by a variety of endogenous (hypoglycemia, decreased blood volume, decreased blood pressure, altered thermoregulation, and distention of colon and bladder) and exogenous (environmental Inhibitors,research,lifescience,medical stress, threat) stressors. Such activation is likely important to survival from a life-threatening situation and serves as a general alarm function.49

The ability of acute Pazopanib order stress to activate both the HPA and LC-NE systems facilitates the encoding and relay of aversively charged emotional memories beginning in the amygdala. The amygdala and the LC inhibit the PFC, and stimulate hypothalamic CRH release. These feedback loops among the PFC, amygdala, hypothalamus, and brain stem noradrenergic neurons contain the elements for a sustained and powerful stress Inhibitors,research,lifescience,medical response.22 Psychological resilience and reduced anxiety responses to stress are probably associated with LC-NE system activation, which stays within

a window of adaptive elevation required to respond to danger, but not so high as to produce incapacity, anxiety, and fear. If unchecked, persistent hyperresponsiveness of the LC-NE system will contribute to chronic anxiety, fear, Inhibitors,research,lifescience,medical intrusive memories, and increased risk of hypertension and cardiovascular disease. In some patients with PD and PTSD, there is evidence of heightened LC-NE activity.50-53 More research Inhibitors,research,lifescience,medical is needed to determine the role of the LC-NE system in GAD and SAD. There is preliminary evidence that β-receptor antagonist treatment shortly after traumatic stress exposure may have beneficial and perhaps preventative effects.54,55 α1 receptor blockade with prazosin has been shown to reduce nightmares and associated sleep disturbances in PTSD.56 Neuropeptide Y Neuropeptide Y (NPY) is among the most abundant neuropeptides in mammalian brain next with high concentrations in the LC57; paraventricular nucleus of the hypothalamus58; septohippocampal neurons59; nucleus of solitary tract; and ventrolateral medulla.60 Moderate levels are found in the amygdala, hippocampus, cerebral cortex, basal ganglia, and the thalamus.61 NPY has been shown to have anxiolytic activity and to impair the consolidation of memories. These effects are mediated at least, in part, by NPY-1 receptors in the amygdala.62-66 The anxiolytic effects of NPY may also involve effects on LC function, since NPY reduces the firing of LC neurons via the NPY-2 receptor.