| Abstract |
The discovery of the infrared pupillometer in the 50s gave impetus to research which in the 60s through to the 80s established a great deal of knowledge on the physiology, pharmacology and psychophysiology of the pupillary test system. Pupillary research in the 90s took advantage of progress made in animal models of conditioned fear and established the close relationship of the fear-inhibited pupillary light reflex and the fear-potentiated startle reflex, two paradigms that are suitable for translational research in fear and anxiety. An additional advantage of the pupillary test system is that it can separate between attentional/general arousal processes reflected in tonic or phasic increases in pupil diameter (a response mediated by increase in sympathetic output to the iris dilator muscle) and fear- or anxiety-related processes that are reflected in the inhibition of the light reflex (mediated by central, supranuclear inhibition of the parasympathetic Edinger-Westphal nucleus and reduced output to the iris constrictor muscle). In this thesis, we exploited these properties of the pupillary test system and studied the effects of serotonergically acting drugs (ketanserin in experiment 1) and non-benzodiazepine anxiolytic drugs (buspirone, propranolol in experiments 2 and 3) on physiological arousal as measured by resting pupil diameter in the dark. Ketanserin, but not buspirone or propranolol had a fully sedative profile in the pupillary test system and other objective and subjective measures of arousal. In experiments 4 and 5 we examined the profiles of ketanserin and buspirone respectively on the fear-inhibited light reflex. We found that buspirone but not ketanserin normalized fear-inhibiton of the light reflex consistent with animal studies on the conceptually similar startle-potentiated startle reflex paradigm and in agreement with the clinical utility of buspirone but not ketanserin in human anxiety disorders. The studies of this thesis advance both the understanding of the pupillary test system as a model of arousal and anxiety as well as the pharmacological mediation of
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human arousal and anxiety. Because the current fear-inhibited light reflex models phasic fear/anxiety, in experiment 6 we developed an alternative light reflex protocol that allows for the study of the onset, time-course and offset of anticipatory fear, which is more relevant to sustained rather than phasic anxiety disorders in humans i.e. generalized anxiety rather than phobic/panic anxiety disorders. We validated this protocol with the established fear-potentiated startle paradigm in humans.
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Φαρμακολογική διερεύνηση του άγχους αναμονής μέσω της εκ φόβου αναστολής του φωτοανακλαστικού στον άνθρωπο
