YOHIMBINE FACILITATED ACOUSTIC - STARTLE IN COMBAT VETERANS WITH POSTTRAUMATIC STRESS DISORDER

Preclinical and clinical studies have suggested that the acoustic star tle reflex (ASR) is a useful model to investigate the neurochemical ba sis of anxiety and fear states. This work has revealed that the anxiog enic alpha-2 receptor antagonist, yohimbine, increases the amplitude o f the ASR in laboratory animals and in healthy human controls, Because of the growing body of data that support the hypothesis that severe s tress results in substantial alterations in noradrenergic neuronal rea ctivity, the present investigation evaluated the effects of yohimbine on the ASR of 18 patients with PTSD and 11 healthy combat controls. Su bjects received IV yohimbine (0.4 mg/kg) or saline placebo on 2 separa te days in a randomized double blind placebo control design, A trial o f two tone frequencies with varied intensity (90, 96, 102, 108, 114 dB ) white noise and instantaneous rise time, was delivered binaurally th rough headphones. Tones were delivered every 25-60 s, for a 40-ms dura tion. Startle testing was performed 80 min post-infusion and lasted 15 -20 min. Yohimbine significantly increased the amplitude, magnitude an d probability of the ASR in combat veterans with PTSD, but did not do so in combat controls. Overall startle was significantly larger in the PTSD subjects; however, this did not account for the differential eff ect of yohimbine, since yohimbine had no significant effect in the con trol group. This study demonstrates an excitatory effect of yohimbine on the amplitude, magnitude and probability of the ASR in PTSD patient s that is not seen in combat controls. In the context of the key role of this reflex in the alarm response, this finding adds to the array o f documented behavioral, biochemical and cardiovascular effects of yoh imbine in humans which support the relationship between increased nora drenergic function and exaggerated startle symptomatology of PTSD.