Date of Award

Spring 1-1-2011

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Integrative Physiology

First Advisor

Robert S. Mazzeo

Second Advisor

Kenneth P. Wright Jr.

Third Advisor

MOnique K. LeBourgeois

Abstract

The intrinsic circadian timing system allows for the temporal organization of many physiological and behavioral events across the 24h light-dark cycle. Both photic (light) and non-photic (e.g., exogenous melatonin) stimuli have been shown to influence the timing of the mammalian circadian system. Furthermore, in non-humans, there is a growing body of evidence to suggest that the integration of photic and non-photic stimuli may induce greater circadian adaptation than either stimulus alone. Understanding how photic and non-photic stimuli influence the human circadian system will help determine the most effective and efficient ways to shift the human circadian clock. Therefore, the aims of this dissertation were to: 1) determine if morning bright light exposure and evening exogenous melatonin administration would produce a circadian phase advance that would be integrated by the human circadian system to produce a greater shift than either stimulus alone; 2) determine whether morning caffeine administration induces a circadian phase advance of the human circadian clock; 3) determine if evening caffeine administration induces a circadian phase delay of the human circadian clock; and 4) determine if evening bright light exposure and evening caffeine administration produces a circadian phase delay that would be integrated by the human circadian system to produce a greater shift than either stimulus alone. The results indicate: 1) morning bright light combined with late afternoon exogenous melatonin induces a greater phase advance of the human circadian clock than either treatment alone; 2) preliminary evidence that caffeine may be able to phase advance the human circadian clock; and 3) exposure to evening caffeine induces a circadian phase delay of the human circadian clock; and 4) exposure to evening bright light combined with evening caffeine does not induce a greater phase shift than either alone. These findings suggest that photic and some non-photic time cues alone and in combination can phase shift the human circadian system. Findings demonstrate for the first time the ability of evening caffeine administration to produce a circadian phase delay in humans, and suggest that morning caffeine administration may attenuate the drift in circadian phase under dim light conditions. These findings have implications for the treatment of circadian sleep disorders and circadian misalignment.

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Physiology Commons

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