Sensitivity of the fear-inhibited light reflex to diazepam

Abstract

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.

Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine

“…This observation is in agreement with numerous previous reports demonstrating the sedative effects of diphenhydramine (for example [32][33][34][35]) and diazepam (for example [6,36,37). Recent evidence suggests that the sedative effects of both drugs may be mediated by the central histaminergic system originating from the tuberomamillary nucleus of hypothalamus.…”

“…The doses of the drugs were selected on the basis of published information and also experience in our laboratory. Diazepam 10 mg consistently evokes a robust sedative effect in laboratory conditions [6,7,18]. Although most studies have used smaller single doses (25 mg or 50 mg) of diphenhydramine [19], it has been reported that a higher dose of 75 mg is required to evoke reproducible robust sedative effects [20].…”

“…The method used here was similar to that used by Bitsios et al [6,18,27]. The sampling rate of the pupillometer was 50 Hz and the detection accuracy was better than 0.05 mm.…”

“…Another class of drug not conforming to the general rule of an association between sedation and miosis are the benzodiazepines. These drugs, although highly sedative, have been reported not to influence pupillary diameter [2][3][4][5][6].…”

“…Another class of drug not conforming to the general rule of an association between sedation and miosis are the benzodiazepines. These drugs, although highly sedative, have been reported not to influence pupillary diameter [2][3][4][5][6]. Diphenhydramine is a first-generation antihistamine [7], which has high affinity for H1 histamine receptors [8,9], without any affinity for H2 histamine receptors [10].…”