Imaging dopamine:
Gespeichert in:
| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2009
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| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | 330 S. Ill., graph. Darst. |
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Datensatz im Suchindex
| _version_ | 1804139113115287552 |
|---|---|
| adam_text | Titel: Imaging dopamine
Autor: Cumming, Paul
Jahr: 2009
Contents
Foreword xiii
Acknowledgments xv
Introduction 1
1. The life history of dopamine 5
1.1. A brief overview of the dopamine pathway 5
1.2. A brief account of the blood-brain barrier 10
1.3. Neurochemical anatomy of the nigrostriatal pathway 11
1.4. Physiology of dopamine neurons 15
1.5. The post-synaptic effects of dopamine 16
1.6. A brief introduction to molecular imaging 17
2. Enzymology of tyrosine hydroxylase 19
2.1. Molecular biology and enzymology 19
2.2. Disorders of tyrosine hydroxylase 20
2.3. Regulation of activity 22
2.4. Autoreceptor modulation of activity 24
2.5. Phosphorylation of tyrosine hydroxylase 25
2.6. Transcriptional regulation 27
3. The assay of tyrosine hydroxylase 29
3.1. Accumulation ofDOPA after treatment with NSD 1015 29
3.2. Superfusion of living striatum with [3H]tyrosine 34
3.3. Intracerebroventricular infusion of [3H]tyrosine 36
3.4. Intravenous injection of [3H)tyrosine 36
3.5. Modeling the metabolism of [3H]tyrosine 37
3.6. Autoradiography in vivo with tyrosine: an introduction
to the analysis of PET data 40
ix
x Contents
4. Enzymology of aromatic amino acid decarboxylase 45
4.1. Kinetic properties of AAADC in vitro 45
4.2. Regulation and transcription of AAADC 48
4.3. AAADC activity in living brain 50
4.4. In vivo metabolism of AAADC substrates 51
5. PET studies of DOPA utilization 54
5.1. General aspects of the quantitation of
FDOPA utilization 54
5.2. Methods for the quantitation of DOPA-PET
studies 57
5.3. The true activity of AAADC in living brain 67
5.4. Other substrates for PET studies of AAADC 68
5.5. Pharmacological modulation of AAADC activity 69
5.6. Clinical FDOPA-PET studies 71
5.7. Personality and cognition 77
6. Conjugation and sulfonation of dopamine
and its metabolites 80
6.1. Biochemistry of COMT 80
6.2. Behavioral correlates of COMT activity 82
6.3. Arylsulfotransferase 83
7. Dopamine synthesis and metabolism rates 85
7.1. Steady-state and the epistemology of dopamine
metabolism 85
7.2. Turnover of dopamine 86
7.3. Turnover of the acidic metabolites 89
7.4. 3-Methoxytyramine 95
8. MAO activity in the brain 99
8.1. Enzymology 99
8.2. Neurochemical anatomy of MAO 101
8.3. Effects of MAO inhibition and knockout on dopamine
transmission 102
8.4. Disorders of MAO and knockouts 103
8.5. MAO activity in vivo 104
8.6. Clinical PET studies of MAO 109
9. Vesicular storage of dopamine ill
9.1. Biochemistry of vesicular monoamine transporters 111
9.2. Chromaffin granules 112
Contents xi
9.3. Regulating and knocking out VMAT2 114
9.4. Ligands and tracers for VMAT2 115
9.5. Clinical PET studies of VAT2 120
10. Dopamine release: from vesicles to behavior 122
10.1. Methods for measuring dopamine release 122
10.2. Concentration gradients for dopamine across the plasma
membrane 127
10.3. The action of psychostimulants 128
10.4. Behavioral correlates of dopamine release 131
11. The plasma membrane dopamine transporter 137
11.1. Molecular biology of DAT and regulation of expression 137
11.2. Functional aspects of DAT, and how to live without it 138
11.3. Ligands for the detection of DAT 141
11.4. Clinical DAT studies 149
12. Dopamine receptors 160
12.1. Pharmacology and biochemistry 160
12.2. Neurochemical anatomy 161
12.3. Dopamine receptor signal transduction 163
12.4. Agonist-induced internalization of dopamine
receptors 165
13. Imaging dopamine Dt receptors 167
13.1. General aspects of Dj receptors 167
13.2. PET ligands for D, receptors 168
13.3. Imaging studies of Dj receptors 171
14. Imaging dopamine D2 receptors 174
14.1. General properties of D2 ligands 174
14.2. Oligomeric associations of dopamine D2 receptors 180
14.3. Effects of denervation on D2 receptors 181
14.4. Competitive binding at D2 receptors in living brain 182
14.5. Clinical studies of dopamine D2 receptors 194
15. Factors influencing D2 binding in living brain 203
15.1. Pharmacological modulation 203
15.2. Clinical studies of psychostimulant-evoked dopamine
release 205
15.3. Other pharmacological challenges altering dopamine receptor
binding 212
xii Contents
15.4. Transcranial magnetic stimulation, deep brain stimulation,
and sensory stimulation 215
15.5. Personality 217
15.6. Pain and stress 218
15.7. Motivation, craving, and placebo 220
16. The absolute abundance of dopamine receptors
in the brain 224
17. Conclusions and perspectives 229
References 234
Index 331
The color plates are between pages 28 and 29, and
pages 223 and 224.
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