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MONOAMINE OXIDASE DEFICIENCY AND EMOTIONAL REACTIVITY:
NEUROCHEMICAL AND DEVELOPMENTAL STUDIES
by
Anna Louise Scott
________________________________________________________________________
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(MOLECULAR PHARMACOLOGY AND TOXICOLOGY)
December 2010
Copyright 2010 Anna Louise Scot
Object Description
| Title | Monoamine oxidase deficiency and emotional reactivity: neurochemical and developmental studies |
| Author | Scott, Anna Louise |
| Author email | annalscott@gmail.com; annascot@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Molecular Pharmacology & Toxicology |
| School | School of Pharmacy |
| Date submitted | 2010 |
| Restricted until | Unrestricted |
| Date published | 2010-11-17 |
| Advisor (committee chair) | Shih, Jean C. |
| Advisor (committee member) |
Duncan, Roger Holschneider, Daniel Bortolato, Marco |
| Abstract | Monoamine oxidases (MAOs) serve a crucial function in the regulation of mood and behavior. The two isoenzymes, MAO A and MAO B, are expressed in a variety of brain and peripheral tissues where they catalyze the oxidative deamination of neurotransmitter and dietary monoamines. MAO A preferentially catabolizes serotonin (5-HT) and norepinephrine (NE), MAO B prefers the trace amine phenylethylamine (PEA), and both catabolize dopamine (DA). In the absence of MAO A, MAO B oxidizes MAO A’s preferred substrates and vice versa, indicating partial functional redundancy.; Despite a wealth of evidence demonstrating that MAO mutations result in deficient monoamine metabolism and maladaptive emotional reactivity, the specific mechanisms underpinning this relationship remain highly elusive. Studies included in this dissertation begin to fill this gap. This work has focused on MAO A and dual MAO A/B mutations that result in deficient metabolism of 5-HT and NE. Knock out (KO) mice harboring these mutations were evaluated using behavioral paradigms designed to explore different facets of emotional responsiveness. These studies were carried out in conjunction with biochemical and cellular assays to elucidate factors that contribute to the emotional impairments exhibited by these lines. Collectively, these studies enhance our understanding of the behavioral phenotypes displayed by MAO A KO and MAO A/B KO mice and highlight novel neurochemical and developmental perturbations which may have a causal role in the emotional disturbances displayed by these lines.; This dissertation (1) Describes a novel line of mice harboring a human-like mutation in MAOA analogous to the cause of a rare disorder featuring impulsive aggressiveness; (2) Provides strong evidence that the phenotype associated with total MAO deficiency features a general dysregyulation in the emotional processing of environmental cues; (3) Highlights nitric oxide as an interesting substrate for certain behavioral disturbances in MAO A KO and MAO A/B KO mice and (4) Defines novel roles for MAOs and 5-HT during embryonic and early postnatal stages of development. Collectively, this work provides new models and mechanisms to understand the consequences of MAO deficiency on the regulation of emotional behaviors. |
| Keyword | monoamine oxidase A; monoamine oxidase B; serotonin; norepinephrine; emotional reactivity; behavioral pharmacology; knock out mice; nitric oxide |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3536 |
| Rights | Scott, Anna Louise |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Scott-4065 |
| Archival file | uscthesesreloadpub_Volume32/etd-Scott-4065.pdf |
Description
| Title | Page 1 |
| Full text | MONOAMINE OXIDASE DEFICIENCY AND EMOTIONAL REACTIVITY: NEUROCHEMICAL AND DEVELOPMENTAL STUDIES by Anna Louise Scott ________________________________________________________________________ A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (MOLECULAR PHARMACOLOGY AND TOXICOLOGY) December 2010 Copyright 2010 Anna Louise Scot |
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