Preclinical and clinical studies have suggested that the acoustic startle reflex (ASR) is a useful model to investigate the neurochemical basis of anxiety and fear states. This work has revealed that the anxiogenic alpha-2 receptor antagonist,
yohimbine, increases the amplitude of the ASR in laboratory animals and in healthy human controls. Because of the growing body of data that support the hypothesis that severe stress results in substantial alterations in noradrenergic neuronal reactivity, the present investigation evaluated the effects of
yohimbine on the ASR of 18 patients with
PTSD and 11 healthy combat controls. Subjects received IV
yohimbine (0.4 mg/kg) or saline placebo on 2 separate days in a randomized double blind placebo control design. A trial of two tone frequencies with varied intensity (90, 96, 102, 108, 114 dB) white noise and instantaneous rise time, was delivered binaurally through headphones. Tones were delivered every 25-60 s, for a 40-ms duration. Startle testing was performed 80 min post-infusion and lasted 15-20 min.
Yohimbine significantly increased the amplitude, magnitude and 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 effect of
yohimbine, since
yohimbine had no significant effect in the control group. This study demonstrates an excitatory effect of
yohimbine on the amplitude, magnitude and probability of the ASR in
PTSD patients that is not seen in combat controls.(ABSTRACT TRUNCATED AT 250 WORDS)