The symptomatology of post-traumatic stress disorder (PTSD) involves sympathetic hyperarousal. Several of these sympathetic symptoms are mediated through end-organ beta2-adrenergic receptors (beta2AR). Increased sympathetic activity in PTSD could therefore be due to increased betaAR function. This study investigated betaAR function in 30 healthy controls and 20 drug-free PTSD patients. BetaAR binding studies were conducted using antagonist-saturation and agonist-displacement experiments. Measures of beta2AR coupling to Gs protein were derived from agonist-displacement experiments. PTSD patients had significantly higher beta2AR density particularly in the high-conformational state and higher beta2AR coupling than controls, as reflected in a higher percentage of receptors in the high conformational state and a higher ratio of the agonist dissociaton constant from the receptor in the low/high-conformational state. Increased betaAR function in PTSD is consistent with the symptomatology of this disorder. Increased betaAR density and coupling may be consistent with downregulation of betaAR density and uncoupling by antidepressants and may underlie their partial efficacy in PTSD. Dysregulation in Gs protein function is postulated and, agonist-mediated regulation of betaAR expression and/or betaAR kinase activity in PTSD should be investigated in future studies.

Various studies suggest ␣ 2 -adrenergic receptor ( ␣ 2 AR) dysregulation in panic disorder (PD). Platelet

Low platelet membrane alpha2-adrenergic receptor (alpha2AR) density and low basal and forskolin-stimulated cyclic adenosine monophosphate responses, which have been reported in post-traumatic stress disorder (PTSD), suggest either abnormal alpha2AR coupling to G(i) protein or dysregulation in post-receptor signal transduction mechanisms. alpha2AR density in the high- and low-conformational states, agonist affinity in both states and coupling to G(i) protein were investigated in 23 drug-free combat PTSD patients and 25 normal controls. alpha2AR coupling measures were not different between PTSD patients and controls. Total alpha2AR density was higher in PTSD patients than controls, due to a higher density of the receptor in the high-conformational state. There were no differences in agonist affinity to the receptor in either conformational state. Results rule out dysregulation in alpha2AR coupling to G(i) protein. Studies of post-receptor signal transduction mechanisms are warranted.

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