Jason Power

Date of Award

December 2022

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical Sciences

First Advisor

Van Doze

Abstract

The adrenergic system plays a key role in the treatment and understanding of the etiology of mental illnesses. Despite antidepressants having the effect of reducing the reuptake of specific neurotransmitters, such as norepinephrine (NE), the mechanism of the antidepressant effect is poorly understood. It is apparent that antidepressants increase the rate of neurogenesis occurring within the hippocampal region of the brain with the hippocampus found to have an increased density around the time of symptom improvement (rate plateaus after 4-8 weeks after treatment). With an increased rate of neurogenesis taking ~1 month to occur, it was hypothesized that treatment with an alpha1A-AR agonist would induce an antidepressant-like action as a potential phenotypical action of the adrenergic system.Although utilizing the alpha1A-AR agonist, Cirazoline, did not demonstrate any significant difference in a 2-week acute treatment or a month-long treatment, significance was found in the behavioral experiments. Males and females have long been divided into separate experimental groups due to their biological differences. Current research is working to disprove the need for separate experiments. In the results from the Cirazoline experiment, sex differences were significantly found among the treated and untreated mice. As such, male and female mice cannot be compared in terms of their equal responses in behavioral experiments. Female mice were found to have more anxiety than males whether treated or untreated, indicating a significant difference when sex was compared independently. In the 24-hour restraint test, significance was found in the Tail Suspension Test (TST) which concluded that after 24 hours of restraining, mice display an acute depressive phenotype Although this was not found in the Forced Swim Test (FST), not all tests are equivalent when evaluating psychosomatic symptoms. The TST not only includes immobility but also does not have the bias of mice being able to float, such as in the FST. By being able to float, mice are less likely to continue to be immobile during the FST when learned. However, the TST does not include this bias as mice are not able to learn that harm will not occur if they give up. This is a key indicator for the learned helplessness model.

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