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J Psychopharmacol. 2008 Nov;22(8):828-35. doi: 10.1177/0269881107083843. Epub 2008 Jan 21.

Effects of threat of electric shock and diazepam on the N1/P2 auditory-evoked potential elicited by low-intensity auditory stimuli.

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  • 1Department of Audiology, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.


The acoustic startle response includes rapid muscular contractions elicited by loud sounds; it may be measured in humans as the electromyographic response of the orbicularis oculi muscle. Enhancement of this response during exposure to threat of electric shock (fear- potentiated startle) is a widely used model of human anxiety. A problem with the use of the startle reflex in studies of human anxiety is the aversiveness of startle-eliciting sounds, which may, in some subjects, exceed the aversiveness of the electric shock itself. We have recently found that the long-latency N1/P2 auditory-evoked potential elicited by loud sounds is subject to fear potentiation. However, it is not known whether N1/P2 potentials elicited by low-intensity sounds, which do not elicit the startle response, are also subject to fear potentiation. This study examined the susceptibility of the N1/P2 potential elicited by low-intensity sounds to fear potentiation, and the effect of the anxiolytic diazepam on the N1/P2 potential in the absence and presence of threat of electric shock. Fifteen male volunteers (18-43 years) participated in three sessions in which they received placebo, diazepam 5 mg and diazepam 10 mg according to a double-blind protocol. Sixty minutes after treatment, auditory-evoked potentials were elicited by 40 ms 1 kHz tones 5, 10, 15, 20 and 25 dB[A] above a background of 70 dB[A]. Recording sessions consisted of eight alternating 2 min THREAT and SAFE blocks; unpredictable shocks (1.8 mA, 50 ms) were delivered to the subject's wrist in THREAT blocks (1-4 shocks per block). The amplitude of the N1/P2 potential increased monotonically as a function of stimulus intensity. The responses were significantly greater during THREAT blocks than during SAFE blocks (fear potentiation). Diazepam attenuated the responses in both the SAFE and THREAT conditions. Fear potentiation of the N1/P2 potential was significantly reduced by diazepam. Diazepam reduced subjective alertness and lowered critical flicker fusion frequency, a measure of arousal. The results suggest that fear potentiation of the N1/P2 potential is not simply a manifestation of the fear-potentiated startle response. The use of low-intensity stimuli may be advantageous in studies of fear potentiation in humans.

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