Date of Award

1998

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

First Advisor

Roger M. Hawk, Ph. D,

Abstract

Four psychoactive drugs were studied using various in vivo nuclear magnetic resonance (NMR) techniques. Trifluoperazine (TFP) was given to several normal rats, whose brains were then studied using in vivo fluorine-19 NMR. Three peaks were detected in the in vivo fluorine spectra: one at -62 ppm, which was due to TFP, and two others at -55 and -75 ppm, which are due to unknown metabolites of TFP. Samples of skin, skull, muscle, and brain were obtained from these rats and extracted for in vitro analysis. The metabolites responsible for the in vivo peak at -75 ppm also appeared in the extract spectra from muscle and brain. The effect of lithium on the proton image of normal rat brain was examined using gradient recalled echo acquisitions. Images acquired before and after dosing the rat with lithium were analyzed by subtraction, Student's t-test, and profile analysis. While the subtraction and statistical tests were inconclusive, the profile analysis indicates that there is about a 3% increase in image intensity over time in rats that received lithium. Finally, the antipsychotics clozapine and haloperidol were examined using in vivo localized NMR spectroscopy. Rats were given the drugs for seven days. Spectra were collected prior to dosing and after the first and last doses to determine if there were any changes in the ratios of N-acetylaspartate to creatine or of choline to creatine. No changes were seen. A point-resolved spectroscopy sequence (PRESS) was modified and used to collect the spectra. The modifications to this sequence and a program that was written to automatically phase the spectral data are described.

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