Date of Award

Spring 2-28-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Steven F. Maier

Second Advisor

Linda R. Watkins

Third Advisor

Robert L. Spencer

Fourth Advisor

Kenneth P. Wright

Fifth Advisor

Soo H. Rhee

Abstract

Stress is a common etiological factor in the development of anxiety disorders and depression. However, there is considerable heterogeneity in how individuals respond to seemingly similar adverse life events. Therefore, it is important to investigate factors contemporaneous to the experience of stress that impart resistance/resilience or contribute to vulnerability. Proper synchronization to the environmental light-dark cycle is necessary for optimal health. In modern society, exposure to environmental disruption (e.g. shift work, air travel, light at night) is commonplace and is linked to an increasing prevalence in anxiety disorders and depression. Thus, here I began to explore whether circadian factors might influence stress outcome.

The first aim of this dissertation was to determine whether a behavioral factor that is known to promote resistance/resilience is regulated by the circadian system. Specifically, I tested whether chronic perturbation of the circadian system would interfere with the acute protective behavioral effects typically produced by active coping in rats (e.g. behavioral control; Chapter 2). Here I present evidence that chronic circadian disruption did not interfere with the protective effect of behavioral control on the stress-induced reduction in social behavior. However, similar to uncontrollable stress, chronic circadian disruption alone was sufficient to interfere with subsequent escape learning, and behavioral control did not rescue this impairment.

The second aim of this dissertation was to determine whether the timing of stressor exposure is a critical determinant of stressor consequences. Specifically, I tested whether stressor exposure during opposite phases of the light-dark cycle produced equivalent behavioral and neurochemical outcomes (Chapter 3). Here I present evidence that rats stressed during their active phase are resistant to the stress-induced reduction in social behavior and potentiated fear, but not behavioral anhedonia. Furthermore, stress-induced activation of serotonin (5-hydroxytryptamine) neurons in the dorsal raphe nucleus (DRN), a region critical for driving stress-induced changes in anxiety and fear, was greater during the light compared to dark phase.

The results from these studies clearly demonstrate that behavioral (e.g. active coping) and temporal (e.g diurnal) factors can potently influence stress outcome. This work highlights the importance of studying circadian variables to elucidate the biological substrates of stress resistance/resilience.

Available for download on Sunday, October 10, 2021

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