THE EFFECTS OF CLONIDINE ON THE FEAR-INHIBITED LIGHT REFLEX

We have shown previously that pupil diameter increases and the amplitu de of the pupillary light reflex is reduced when subjects are under th reat of an aversive event (electric shock), and that light reflex ampl itude correlates negatively with subjective anxiety. Furthermore, we h ave shown that the threat-induced reduction in light reflex amplitude is sensitive to the effect of the anxiolytic drug diazepam. We have su ggested that the 'fear-inhibited light reflex' paradigm could be used as a laboratory model of human anxiety. In the present study, we exami ned whether a single oral dose (200 mu g) of the sedative-sympatholyti c drug clonidine would antagonize the effects of threat on the pupilla ry light reflex. Twelve healthy male volunteers participated in two se ssions separated by seven days in which they ingested clonidine 200 mg or placebo in a double-blind, balanced, crossover design. Light stimu li (0.43 mW/cm(2), 200 msec) were generated by a green (peak wavelengt h 565 nm) light-emitting diode, and pupil diameter was monitored by co mputerized 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 anticipat ed ('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 experim ent. Following each 'threat' or 'safe' block, subjects rated their anx iety using visual analogue scales. Two-factor ANOVA (treatment x condi tion) showed that clonidine treatment antagonized both the threat-indu ced increase in pupil diameter and the threat-induced reduction in lig ht 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 a lertness but not subjective anxiety in the 'threat' condition. These f indings suggest that the mutual antagonism between clonidine and threa t is likely to reflect the opposite effects of the two variables on th e central noradrenergic control of pupillary functions, rather than a specific anxiolytic effect.