The effects of clonidine on the fear-inhibited light reflex

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. Furthermore, we have shown that the threat-induced reduction in light reflex amplitude is sensitive to the effect of the anxiolytic drug diazepam. 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 a single oral dose (200 mu g) of the sedative-sympatholytic drug clonidine would antagonize the effects of threat on the pupillary light reflex. Twelve healthy male volunteers participated in two sessions separated by seven days in which they ingested clonidine 200 mg or placebo in a double-blind, balanced, crossover design. Light stimuli (0.43 mW/cm(2), 200 msec) were generated by a green (peak wavelength 565 nm) light-emitting diode, and pupil diameter was monitored by computerized binocular infrared television pupillometry in the dark. The light reflex response was recorded during either the anticipation of a shock ('threat' blocks) or periods in which no shocks were anticipated ('safe' blocks). The shock was a single square wave current pulse (1.5 mA, 50 msec) applied to the median nerve at the end of the experiment. Following each 'threat' or 'safe' block, subjects rated their anxiety using visual analogue scales. Two-factor ANOVA (treatment x condition) showed that clonidine treatment antagonized both the threat-induced increase in pupil diameter and the threat-induced reduction in light reflex amplitude. These effects, however, were not threat-specific since clonidine also reduced pupil diameter and enhanced light reflex amplitude in the 'safe' condition. Clonidine also reduced subjective alertness but not subjective anxiety in the 'threat' condition. These findings suggest that the mutual antagonism between clonidine and threat is likely to reflect the opposite effects of the two variables on the central noradrenergic control of pupillary functions, rather than a specific anxiolytic effect.