Imaging Dopamine

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ISBN: 9780521790024 | 0521790026
Cover: Hardcover
Copyright: 4/27/2009

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Since its discovery 50 years ago, brain dopamine has been implicated in the control of movement and cognition, and is concerned with diverse brain diseases such as Parkinson's disease, schizophrenia and drug addiction. This book is an illustrated biography of the dopamine molecule, from its synthesis in the brain to its signalling mechanisms and ultimately to its metabolic breakdown. Using colour illustrations of positron emission tomography (PET) scans, each chapter presents a specific stage in the biochemical pathway for dopamine. Writing for researchers and graduate students, Paul Cumming presents a compilation of all that has been learned about dopamine through molecular imaging, a technology which allows the measurement of formerly invisible processes in the living brain. He reviews current technical controversies in the interpretation of dopamine imaging, and presents key results illuminating brain dopamine in illness and health.

Foreword	p. xiii
Acknowledgments	p. xv
Introduction	p. 1
The life history of dopamine	p. 5
A brief overview of the dopamine pathway	p. 5
A brief account of the blood-brain barrier	p. 10
Neurochemical anatomy of the nigrostriatal pathway	p. 11
Physiology of dopamine neurons	p. 15
The post-synaptic effects of dopamine	p. 16
A brief introduction to molecular imaging	p. 17
Enzymology of tyrosine hydroxylase	p. 19
Molecular biology and enzymology	p. 19
Disorders of tyrosine hydroxylase	p. 20
Regulation of activity	p. 22
Autoreceptor modulation of activity	p. 24
Phosphorylation of tyrosine hydroxylase	p. 25
Transcriptional regulation	p. 27
The assay of tyrosine hydroxylase	p. 29
Accumulation of DOPA after treatment with NSD 1015	p. 29
Superfusion of living striatum with [3H]tyrosine	p. 34
Intracerebroventricular infusion of [3H]tyrosine	p. 36
Intravenous injection of [3H]tyrosine	p. 36
Modeling the metabolism of [3H]tyrosine	p. 37
Autoradiography in vivo with tyrosine: an introduction to the analysis of PET data	p. 40
Enzymology of aromatic amino acid decarboxylase	p. 45
Kinetic properties of AAADC in vitro	p. 45
Regulation and transcription of AAADC	p. 48
AAADC activity in living brain	p. 50
In vivo metabolism of AAADC substrates	p. 51
PET studies of DOPA utilization	p. 54
General aspects of the quantitation of FDOPA utilization	p. 54
Methods for the quantitation of DOPA-PET studies	p. 57
The true activity of AAADC in living brain	p. 67
Other substrates for PET studies of AAADC	p. 68
Pharmacological modulation of AAADC activity	p. 69
Clinical FDOPA-PET studies	p. 71
Personality and cognition	p. 77
Conjugation and sulfonation of dopamine and its metabolites	p. 80
Biochemistry of COMT	p. 80
Behavioral correlates of COMT activity	p. 82
Arylsulfotransferase	p. 83
Dopamine synthesis and metabolism rates	p. 85
Steady-state and the epistemology of dopamine metabolism	p. 85
Turnover of dopamine	p. 86
Turnover of the acidic metabolites	p. 89
3-Methoxytyramine	p. 95
MAO activity in the brain	p. 99
Enzymology	p. 99
Neurochemical anatomy of MAO	p. 101
Effects of MAO inhibition and knockout on dopamine transmission	p. 102
Disorders of MAO and knockouts	p. 103
MAO activity in vivo	p. 104
Clinical PET studies of MAO	p. 109
Vesicular storage of dopamine	p. 111
Biochemistry of vesicular monoamine transporters	p. 111
Chromaffin granules	p. 112
Regulating and knocking out VMAT2	p. 114
Ligands and tracers for VMAT2	p. 115
Clinical PET studies of VAT2	p. 120
Dopamine release: from vesicles to behavior	p. 122
Methods for measuring dopamine release	p. 122
Concentration gradients for dopamine across the plasma membrane	p. 127
The action of psychostimulants	p. 128
Behavioral correlates of dopamine release	p. 131
The plasma membrane dopamine transporter	p. 137
Molecular biology of DAT and regulation of expression	p. 137
Functional aspects of DAT, and how to live without it	p. 138
Ligands for the detection of DAT	p. 141
Clinical DAT studies	p. 149
Dopamine receptors	p. 160
Pharmacology and biochemistry	p. 160
Neurochemical anatomy	p. 161
Dopamine receptor signal transduction	p. 163
Agonist-induced internalization of dopamine receptors	p. 165
Imaging dopamine D1 receptors	p. 167
General aspects of D1 receptors	p. 167
PET ligands for D1 receptors	p. 168
Imaging studies of D1 receptors	p. 171
Imaging dopamine D2 receptors	p. 174
General properties of D2 ligands	p. 174
Oligomeric associations of dopamine D2 receptors	p. 180
Effects of denervation on D2 receptors	p. 181
Competitive binding at D2 receptors in living brain	p. 182
Clinical studies of dopamine D2 receptors	p. 194
Factors influencing D2 binding in living brain	p. 203
Pharmacological modulation	p. 203
Clinical studies of psychostimulant-evoked dopamine release	p. 205
Other pharmacological challenges altering dopamine receptor binding	p. 212
Transcranial magnetic stimulation, deep brain stimulation, and sensory stimulation	p. 215
Personality	p. 217
Pain and stress	p. 218
Motivation, craving, and placebo	p. 220
The absolute abundance of dopamine receptors in the brain	p. 224
Conclusions and perspectives	p. 229
References	p. 234
Index	p. 331
Table of Contents provided by Ingram. All Rights Reserved.

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Imaging Dopamine

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Imaging Dopamine

Summary

Author Biography

Table of Contents

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