26 Southwick et al27 found that after receiving yohimbine, a subset of PTSD patients not only exhibited physiological arousal such as increased heart rate and blood pressure, but also developed severe anxiety symptoms including acute panic

attacks and increased PTSD symptoms such as intrusive thoughts, flashbacks, and emotional numbing. Yohimbine did not elicit similar responses in trauma-exposed controls without PTSD. Morgan et al28 demonstrated that yohimbine infusion Inhibitors,research,lifescience,medical enhanced acoustic startle responses in combat veterans with PTSD, but did not affect startle responses in combat veterans without PTSD. Consistent with psychophysiologic findings, these result further support the hypothesis that increased noradrenergic responsivity is a core Thiazovivin mouse biological feature of PTSD. Neuroendocrine changes in PTSD Baseline neuroendocrine changes In addition to activating the noradrenergic system, exposure to acute stress elicits important neuroendocrine changes that are modulated by the HPA axis. In response Inhibitors,research,lifescience,medical to acute stress, corticotropin-releasing

hormone (CRH) is released from nuclei in the hypothalamus, amygdala, and cortex.29 CRH is a 41-amino-acid peptide that is transported to the anterior lobe of the pituitary gland Inhibitors,research,lifescience,medical where it stimulates pituitary secretion of adrenocorticotropic hormone (ACTH). ACTH enters the Inhibitors,research,lifescience,medical systemic circulation and binds

to cells in the adrenal cortex, thereby stimulating the secretion of Cortisol. Cortisol is the primary stress hormone. Cortisol binds to the type I and type II glucocorticoid receptors that are present on cell membranes and activates a cascade of physiologic stress responses involving altered metabolism, increased cellular uptake of glucose, modulation of immune activity, and induction of hepatic enzymes. This has been reviewed by Michelson et al.30 Cortisol also blocks Inhibitors,research,lifescience,medical further secretion of CRH and ACTH, thereby curtailing the acute stress response once the stress is over. This is a crucial function of Cortisol, since uncontrolled activation of Bay 11-7085 acute stress hormones can significantly harm host tissue. There is clear evidence from animal studies that persistent activation of the HPA axis by chronic and repetitive stress can have deleterious effects such as the acceleration of aging, disruption of reproductive function, immunosuppression, and reduced ability to fight cancers: these findings have been reviewed by Johnson et al.31 Noting that increased HPA axis activity is associated with chronic stress in preclinical studies, investigators initially predicted that individuals with PTSD would have elevated plasma Cortisol levels and would fail to suppress Cortisol levels after being administered dexamethasone.