Defense Date

1992

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Pharmaceutical Sciences

First Advisor

William H. Barr

Abstract

The objective of this investigation was to evaluate quantitative electroencephalography (EEG) as a measure of CNS stimulation. The reproducibility and sensitivity of quantitative EEG was compared to neuroendocrine, mood, and psychomotor performance measures.

The study was conducted in two parts. The first part investigated the inter- and intra-individual variability associated with a series of pharmacological response measures under baseline (no drug) conditions. It was an open-label pilot study in which eight healthy male volunteers underwent a series of tests (EEG, visual continuous performance task (CPT), a finger tapping task, and self-rated mood scales) repeated eight times over a 12 hour period on three occasions, one week apart. The second part evaluated the sensitivity of quantitative EEG to dextroamphetamine (DA) compared to other response measures. It was a double-blind, placebo-controlled, four-period crossover study in eight healthy male volunteers. Subjects received 5 mg, 10 mg, or 20 mg DA or placebo orally, and underwent the same series of tests as well as blood collection for serum prolactin and DA determination, eight times over a 12 hour period. A GC method allowing quantitation of 2ng/mL DA in serum was developed.

The greatest between-day, within-day, and intrasubject variability was associated with quantitative EEG. Learning effects were observed for the psychometric tests, and first session effects were apparent for several of the tests including the EEG. EEG response to DA was observed only in the 3 subjects who had baseline alpha activity greater than 35%. There was a statistically significant decrease in serum prolactin levels after DA administration, with the largest decrease observed after the 5 mg dose. Mood scales showed that 3 of 9 subjects experienced dysphoria after DA dosing. The effect on mood was generally greater as the dose increased. One subject was discontinued from the study because he experienced intense dysphoria after the 5 mg dose. Doses could not be distinguished based on the results of the psychometric tests. Effects on mood, serum prolactin levels, and performance as measured by CPI and finger tapping were not correlated with the EEG changes observed. Pharmacokinetic evaluation showed that the rate of DA absorption appears to decrease as the dose increases.

Quantitative EEG conducted under our study conditions and study population was not more sensitive for the assessment of CNS stimulation than the other response measures evaluated. The sensitivity may be improved by screening volunteers to select subjects with higher background alpha activity.

Comments

Scanned, with permission from the author, from the original print version, which resides in University Archives.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

6-19-2018

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