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The contribution of ammonia to methamphetamine neurotoxicity


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The contribution of ammonia to methamphetamine neurotoxicity
Contents
Abstract
Acknowledgements
Contents
List of Figures
List of Abbreviations
1 General Introduction to Methamphetamine Neurotoxicity, Liver Damage and Ammonia
1.1 Methamphetamine Use
1.2 Acute Effects of METH on Neurotransmitter release
1.3 Acute Behavioral Effects of METH Exposure
1.4 Persistent Dopamine and Serotonin Terminal Damage
1.5 Neuronal Cell Death
1.6 Long Term Behavioral Consequences of METH Exposure
1.7 Mechanisms of Neurotoxicity
1.7.1 Excitotoxicity
1.7.2 Oxidative Stress
1.7.3 Altered Metabolism and Mitochondrial Damage
1.8 Emerging Mechanisms of Toxicity
1.8.1 Inflammation
1.8.2 Blood Brain Barrier Damage
1.8.3 Peripheral Organ Damage
1.9 METH-Induced Liver Damage
1.10 Ammonia and Neurotoxicity
1.11 Summary of Past Findings and Gaps in Knowledge
1.12 Hypotheses
2 Methamphetamine causes Acute Hyperthermia-Dependent Liver Damage
2.1 Introduction
2.2 Methods
Rat Treatment
Transmission Electron Microscopy
Hematoxylin and Eosin Staining
Asparate Aminotransferase and Alanine Aminotransferase Determination
Statistical Methods
2.3 Results
METH and Liver Damage
METH and Ultrastructural Liver Damage
Environmental Cooling and Methamphetamine-Induced Hyperthermia
Hyperthermia and METH-Induced Changes in Liver Morphology
Hyperthermia and METH-Induced Hepatocellular Damage
2.4 Discussion
3 Peripheral Ammonia Mediates Methamphetamine Neurotoxicity
3.1 Introduction
3.2 Methods
Rat Treatment
Plasma Ammonia Determination
In-Vivo Microdialysis
Brain Ammonia Determination
HPLC Analysis of Monoamine Tissue Content
Western Blot for DAT Immunoreactivity
Mass Spectroscopy
Statistical Analysis
3.3 Results
METH and plasma and ammonia
Effect of Hyperthermia on METH-Induced Increases in Plasma Ammonia
METH and Brain Ammonia
METH and Increased Peripheral Ammonia Excretion
Local Administration of METH and Ammonia
3.4 Discussion
4 Contribution of Ammonia to Methamphetamine-Induced Increases in Extracellular Glutamate and Excitotoxicity
4.1 Introduction
4.2 Methods
Rat Treatment
HPLC Analysis of Monoamine Tissue Content
HPLC Analysis of Glutamate
In-Vivo Microdialysis
Spectrin Breakdown Product (SBP) Analysis
Glutamine Synthetase Protein Level Measurement
Glutamine Synthetase Activity Assay
Statistical Analysis
4.3 Results
Effect of AMPA Receptor Antagonism on Local Administration of METH and Ammonia
Effect of Locally Administered Ammonia on Extracellular Glutamate
Effect of Ammonia on Systemic-METH-Induced Increases in Extracellular Glutamate
Effect of Ammonia on Calpain-Mediated Spectrin Proteolysis
Effect of METH on Glutamine Synthetase Protein Levels
Effect of METH on Glutamine Synthetase Activity
4.4 Discussion
5 General Discussion of Findings
5.1 Summary of Findings
5.2 General Discussion
References 
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