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Journal of Psychopharmacology
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0269881107083843v1
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Article

Effects of threat of electric shockand diazepam on the N1/P2auditory-evoked potential elicited by low-intensity auditory stimuli

Khayria Al-Abduljawad1*, F. Baqui2, R.W. Langley2, C.M. Bradshaw2, and E. Szabadi2

1 Department of Audiology, College of Applied Medical Sciences, King Saud University,Riyadh 11656, Saudi Arabia.
2 Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Nottingham, UK

* To whom correspondence should be addressed.


   Abstract

The acoustic startle response includes rapid muscular contractionselicited by loud sounds; it may be measured in humans as the electromyographicresponse of the orbicularis oculi muscle. Enhancementof this response during exposure to threat of electric shock (fearpotentiatedstartle) is a widely used model of human anxiety. A problemwith the use of the startle reflex in studies of human anxiety is theaversiveness of startle-eliciting sounds, which may, in some subjects,exceed the aversiveness of the electric shock itself. We have recentlyfound that the long-latency N1/P2 auditory-evoked potential elicited byloud sounds is subject to fear potentiation. However, it is not knownwhether N1/P2 potentials elicited by low-intensity sounds, which do notelicit the startle response, are also subject to fear potentiation. Thisstudy examined the susceptibility of the N1/P2 potential elicited by lowintensitysounds to fear potentiation, and the effect of the anxiolyticdiazepam on the N1/P2 potential in the absence and presence of threatof electric shock. Fifteen male volunteers (18-43 years) participated inthree sessions in which they received placebo, diazepam 5mg anddiazepam 10mg according to a double-blind protocol. Sixty minutes aftertreatment, auditory-evoked potentials were elicited by 40ms 1 kHz tones5, 10, 15, 20 and 25 dB[A] above a background of 70 dB[A]. Recordingsessions consisted of eight alternating 2 min THREAT and SAFE blocks;unpredictable shocks (1.8 mA, 50ms) were delivered to the subject'swrist in THREAT blocks (1-4 shocks per block). The amplitude of theN1/P2 potential increased monotonically as a function of stimulus intensity.The responses were significantly greater during THREAT blocks thanduring SAFE blocks (fear potentiation). Diazepam attenuated theresponses in both the SAFE and THREAT conditions. Fear potentiation ofthe N1/P2 potential was significantly reduced by diazepam. Diazepamreduced subjective alertness and lowered critical flicker fusion frequency,a measure of arousal. The results suggest that fear potentiation of theN1/P2 potential is not simply a manifestation of the fear-potentiatedstartle response. The use of low-intensity stimuli may be advantageous instudies of fear potentiation in humans.

Key Words: N1/P2 auditory-evoked potential, diazepam, fear potentiation, humans

First published on January 21, 2008, doi:10.1177/0269881107083843

Journal of Psychopharmacology 2008;22:828.

A more recent version of this article appeared on November 1, 2008


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