Bitsios P, Szabadi E, Bradshaw C M
Department of Psychiatry, Queen's Medical Centre, Nottingham, UK.
Psychopharmacology (Berl). 1998 Jan;135(1):93-8. doi: 10.1007/s002130050489.
We have shown previously that pupil diameter increases and the amplitude of the pupillary light reflex is reduced when subjects are under threat of an aversive event (electric shock), and that light reflex amplitude correlates negatively with subjective anxiety. We have suggested that the "fear-inhibited light reflex" paradigm could be used as a laboratory model of human anxiety. In the present study, we examined whether two doses (5 mg and 10 mg) of the anxiolytic drug diazepam would antagonize the effects of threat on the pupillary light reflex. Twelve healthy male volunteers participated in three weekly sessions, each associated with one of three treatments (diazepam 5 mg or 10 mg or placebo) in a double-blind, balanced, cross-over design. The light reflex was recorded during either the anticipation of a shock ("threat" blocks) or periods in which no shocks were anticipated ("safe" blocks). At the end of each "threat" or "safe" block, subjects rated their anxiety using visual analogue scales. Two-factor ANOVA (treatment x condition) showed that diazepam treatment antagonized the effect of threat on light reflex amplitude in a dose-dependent manner but it did not affect the threat-induced increase in pupil diameter. Diazepam had no effect on the pupillary light reflex in the "safe" condition. Diazepam also reduced subjective anxiety and alertness in the threat condition. These results show the sensitivity of the threat-induced reduction of light reflex amplitude to anxiolytic drugs, and provide further evidence for the utility of the fear-inhibited light reflex paradigm as a laboratory model of human anxiety.
我们之前已经表明，当受试者面临厌恶事件（电击）的威胁时，瞳孔直径会增大，瞳孔对光反射的幅度会减小，并且光反射幅度与主观焦虑呈负相关。我们曾提出，“恐惧抑制光反射”范式可作为人类焦虑的实验室模型。在本研究中，我们检验了两种剂量（5毫克和10毫克）的抗焦虑药物地西泮是否会拮抗威胁对瞳孔对光反射的影响。12名健康男性志愿者参加了为期三周的实验，每次实验与三种治疗方法（5毫克或10毫克地西泮或安慰剂）中的一种相关，采用双盲、平衡、交叉设计。在预期电击时（“威胁”时段）或未预期电击时（“安全”时段）记录光反射。在每个“威胁”或“安全”时段结束时，受试者使用视觉模拟量表对自己的焦虑程度进行评分。双因素方差分析（治疗×状态）表明，地西泮治疗以剂量依赖的方式拮抗了威胁对光反射幅度的影响，但不影响威胁引起的瞳孔直径增加。地西泮在“安全”状态下对瞳孔对光反射没有影响。地西泮还降低了威胁状态下的主观焦虑和警觉性。这些结果表明了威胁引起的光反射幅度降低对抗焦虑药物的敏感性，并为恐惧抑制光反射范式作为人类焦虑的实验室模型的实用性提供了进一步的证据。
