Date of Award

Spring 5-2002

Document Type

Thesis

Degree Name

Honors College Theses

Department

Chemistry

First Advisor

Dr. William H. Jacob

Second Advisor

Dr. Joyce W. O'Rourke

Abstract

Oxidative damage resulting from generation of oxygen-derived free radicals is thought to be the cause of age-related dysfunction in key organs and tissues. Recent studies suggest that the GABA neurotransmitter system modulates the extent of oxidative damage. If this is true, then a drug that alters GABA neurotransmission, such as diazepam, a drug that facilitates GABA neurotransmission, was tested for its efficacy to lessen oxidative damage to the brain tissue. A total of sixteen Swiss Webster mice were implanted subcutaneously with osmotic mini pumps that provided a constant delivery (3.5 mg/Kg/day) of either diazepam (n=8) or vehicle (50% dimethyl sulfoxide/ 50% propylene glycol, n=8), over a period of two weeks. The mice were placed in activity chambers on day 4 and day 13 of the study to test thigmotaxis, an indicator of anxiolytic effects. Body weight and food intake were monitored throughout the study. The mice were euthanized on day 14 and the brains were removed for biochemical analyses of oxidative damage, total thiols, and protein carbonyl content. There was no difference in weight gain and food intake between the control and the experimental groups. In total thiols and carbonyl there were no significant differences. I conclude that the dosage of diazepam was not high enough to affect the oxidative damage.

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