All ETDs from UAB

Advisory Committee Chair

Elizabeth Gardner

Advisory Committee Members

Jason Linville

Lori L McMahon

Document Type

Thesis

Date of Award

2018

Degree Name by School

Master of Science in Forensic Science (MSFS) College of Arts and Sciences

Abstract

Ketamine is a dissociative anesthetic that interacts with the glutamatergic system, acting as an N-methyl-D-aspartate (NMDA) receptor antagonist. At higher doses, ketamine produces negative psychotomimetic side effects, including hallucinations and delirium, leading to its abuse in the 1980s and 90s. Recently, it has been determined that at sub-anesthetic doses, it is a fast-acting antidepressant. Because ketamine elicits fast and long-lasting antidepressant responses in patients, it is being studied as a possible treatment option for those with major depressive disorder and treatment-resistant depression. Further, studies have shown that men and women respond to ketamine treatments differently, especially in long-term treatment, suggesting that gonadal hormones may play a role in how ketamine interacts with the brain. Dr. Lori McMahon, Allie Widman, and Nateka Jackson in the Cell, Developmental, and Integrative Biology Department at the University of Alabama at Birmingham are studying the differences in male and female responses to ketamine. The toxicological results from this graduate research project will be combined with the behavioral observations of the rats by the McMahon group to better understand the differences in how the genders metabolize ketamine. For this research, female rats were ovariectomized (OVX) and half received estrogen (OVX/E2). All of the rats received injections of ketamine and were sacrificed at two time points, either 0 or 30 minutes. Ketamine and norketamine (NK) were quantified in biological tissue collected from the cerebellum, prefrontal cortex (PFC), hippocampus, liver, and plasma of the rats. The results of this study indicate that ketamine is quickly distributed to the brain, specifically in the PFC, and is cleared from the tissues by 30 minutes. The NK concentration was greatest in the tissues at time 30 minutes, particularly in the PFC and liver. The main difference between the OVX and OVX/E2 rats was the amount of NK at time 30 minutes. The OVX/E2 rats had more NK in the tissue samples, however, the difference is not statistically significant. Future studies can include quantitating other metabolites, such as hydroxynorketamine (HNK), to better understand how genders metabolize ketamine differently. Further, rats could be given multiple doses to evaluate the effects of ketamine over long-term treatment.

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