Date of Award

Spring 1-1-2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Integrative Physiology

First Advisor

Monika Fleshner

Second Advisor

Christopher Lowry

Third Advisor

Steven Maier

Abstract

Stress-related mood disorders constitute some of the most common afflictions currently affecting public health. Despite past advances in clinical diagnostics, as well as the existence of pre-clinical animal models, new therapeutic discovery has been limited. Investigations into phenomena which reduce the incidence of stress-related psychiatric disorders, such as exercise, may reveal novel preventative and therapeutic options. While increasing evidence suggests a crucial role of the central serotonin (5-HT) system in the behavioral consequences of stress, a better understanding of the neurobiological substrates involved in the development and expression of anxiety and depression is necessary.

One relevant target in the etiology and treatment of stress-related mood disorders is the 5-HT2C receptor (5-HT2CR). The studies performed in this dissertation seek to elucidate the role of 5-HT2CR in stress-induced anxiety, as well as the anxiolytic effects of exercise. In chapter 2, we delineate the role 5-HT2CR in specific brain regions implicated in the expression of stress-induced anxiety behaviors. The results from these studies demonstrate that the involvement of 5-HT2CR activation in stress-induced, anxiety-like behaviors is regionally specific.

In chapter 3, we identify the 5-HT2CR a potential target for the anxiolytic effects of exercise. Physical activity has been associated with a reduction in the incidence and severity of psychiatric disorders such as anxiety. Similarly, voluntary wheel running can reduce anxiety-like behaviors in laboratory rats. The mechanisms underlying the anxiolytic properties of exercise, however, remain relatively unknown. We tested the hypothesis that voluntary wheel running prevents the behavioral consequences of 5-HT2CR activation in the basolateral amygdala (BLA) and dorsal striatum (DS). We found that voluntary wheel running reduced the behavioral effects produced by 5-HT2CR activation and reduced levels of 5-HT2CR mRNA in the both the BLA and the DS.

Overall, this dissertation extends previous work identifying the 5-HT2CR as a relevant target in the treatment of stress-related anxiety disorders and implicates 5-HT2CR in the anxiolytic effects of physical activity.

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