Al-Abduljawad K A, Baqui F, Langley R W, Bradshaw C M, Szabadi E
Department of Audiology, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
J Psychopharmacol. 2008 Nov;22(8):828-35. doi: 10.1177/0269881107083843. Epub 2008 Jan 21.
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.
听觉惊跳反应包括由响亮声音引发的快速肌肉收缩；在人类中，它可以通过眼轮匝肌的肌电图反应来测量。在暴露于电击威胁期间这种反应的增强（恐惧增强惊跳）是一种广泛使用的人类焦虑模型。在人类焦虑研究中使用惊跳反射的一个问题是引发惊跳的声音具有厌恶性，在某些受试者中，这种厌恶性可能超过电击本身的厌恶性。我们最近发现，由响亮声音引发的长潜伏期N1/P2听觉诱发电位会受到恐惧增强作用。然而，尚不清楚由不引发惊跳反应的低强度声音引发的N1/P2电位是否也会受到恐惧增强作用。本研究考察了由低强度声音引发的N1/P2电位对恐惧增强作用的易感性，以及抗焦虑药物地西泮在有无电击威胁情况下对N1/P2电位的影响。15名男性志愿者（18 - 43岁）参加了三个阶段的实验，按照双盲方案，他们分别接受安慰剂、5毫克地西泮和10毫克地西泮。治疗60分钟后，在70 dB[A]的背景之上，用40毫秒、1千赫的纯音，强度分别为高于背景5、10、15、20和25 dB[A]来引发听觉诱发电位。记录阶段由八个交替的2分钟“威胁”和“安全”时段组成；在“威胁”时段（每个时段1 - 4次电击）向受试者的手腕施加不可预测的电击（1.8毫安，50毫秒）。N1/P2电位的幅度随刺激强度单调增加。在“威胁”时段的反应显著大于“安全”时段（恐惧增强）。地西泮在“安全”和“威胁”两种情况下均减弱了反应。地西泮显著降低了N1/P2电位的恐惧增强作用。地西泮降低了主观警觉性，并降低了临界闪烁融合频率，这是一种觉醒程度的指标。结果表明，N1/P2电位的恐惧增强作用并非仅仅是恐惧增强惊跳反应的表现。在人类恐惧增强作用的研究中，使用低强度刺激可能具有优势。
