Elsevier

Biological Psychiatry

Volume 60, Issue 7, 1 October 2006, Pages 760-766
Biological Psychiatry

Original article
The Benzodiazepine Alprazolam Dissociates Contextual Fear from Cued Fear in Humans as Assessed by Fear-potentiated Startle

https://doi.org/10.1016/j.biopsych.2005.11.027Get rights and content

Background

The startle reflex is potentiated by aversive states. It has been proposed that phasic startle potentiation to a threat cue and sustained startle potentiation to contextual stimuli reflect distinct processes mediated by different brain structures. The present study tested the hypothesis that alprazolam would reduce the sustained startle potentiation to contextual threats but not the startle potentiation to a threat cue.

Methods

Sixteen healthy subjects received each of four treatments: placebo, .5 mg of alprazolam, 1 mg of alprazolam, and 50 mg of diphenhydramine (Benadryl) in a crossover design. Participants were exposed to three conditions, including one in which predictable aversive shocks were signaled by a cue, a second in which shocks were administered unpredictably, and a third condition in which no shocks were anticipated. Acoustic startle were delivered regularly across conditions.

Results

Phasic startle potentiation to the threat cue in the predictable condition was not affected by alprazolam. In contrast, the sustained increase in startle in the predictable and unpredictable conditions was reduced significantly by the high dose of alprazolam.

Conclusions

Startle responses to an explicit threat cue and to an aversive context are psychopharmacologically distinct, suggesting that they may represent functionally dissociable aversive states.

Section snippets

Participants

Participants were healthy volunteers who gave written informed consent that had been approved by the National Institutes of Mental Health Human Investigation Review Board. Inclusion criteria included the following: (1) no past or current psychiatric disorders as per Structured Clinical Interview for DSM-IV (SCID; First et al 1995), (2) no medical condition that interfered with the objectives of the study as established by a physician, and (3) no use of illicit drugs or psychoactive medications

Cued Fear

The results in each condition and in each treatment are presented in Table 1.Figure 1A displays the magnitude of fear-potentiated startle (cue minus ITI). There was a significant main effect of condition [F(2,30) = 11.9, p = .001, GG-ϵ = .65], reflecting greater fear-potentiated startle during the cue in the U condition, compared to the N and P condition. These effects were not affected by treatment, as reflected by a lack of treatment main effect [F(3,45) = .03, ns] and treatment × condition

Discussion

The present study sought to establish a psychopharmacological distinction by using the benzodiazepine alprazolam between a phasic aversive response to a threat cue (cued fear) and a more sustained aversive response associated with the experimental context in which shocks are anticipated (contextual anxiety). The experimental model to elicit these two aversive states was based on preclinical data in rodents (Davis 1998) and on empirical work in our laboratory that used the threat of predictable

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