The last decades of research have not only fundamentally expanded our view on serotonin but also revealed in much more detail an astonishing complexity of this system, which comprises a multitude of receptors and signalling pathways. A detailed view on its role in basal, but also complex, behaviours emerged, and, was presented in a number of single review articles. Although much is known now, the serotonergic system is still a fast growing field of research contributing to our present understanding of the brains function during normal and disturbed behaviour.
This handbook aims towards a detailed and comprehensive overview over the many facets of behavioural serotonin research. As such, it will provide the most up to date and thorough reading concerning the serotonergic systems control of behaviour and mood in animals and humans. The goal is to create a systematic overview and first hand reference that can be used by students and scholars alike in the fields of genetics, anatomy, pharmacology, physiology, behavioural neuroscience, pathology, and psychiatry. The chapters in this book will be written by leading scientists in this field. Most of them have already written excellent reviews in their field of expertise.
The book is divided in 4 sections. After an historical introduction, illustrating the growth of ideas about serotonin function in behaviour of the last forty years, section A will focus on the functional anatomy of the serotonergic system. Section B provides a review of the neurophysiology of the serotonergic system and its single components. In section C the involvement of serotonin in behavioural organization will be discussed in great detail, while section D deals with the role of serotonin in behavioural pathologies and psychiatric disorders.
* The first handbook broadly discussing the behavioral neurobiology of the serotonorgic transmitter system
* Co-edited by one of the pioneers and opinion leaders of the past decades, Barry Jacobs (Princeton), with an international list (10 countries) of highly regarded contributors providing over 50 chapters, and including the leaders in the field in number of articles and citations: K. P. Lesch, T. Sharp, A. Caspi, P. Blier, G.K. Aghajanian, E. C. Azmitia, and others
* The only integrated and complete resource on the market containing the best information integrating international research, providing a global perspective to an international community.
* Of great value not only for researchers and experts, but also for students and clinicians as a background reference.
Serotonin (5-hydroxytryptamine, often cited as 5-HT) is one of the major excitatory neurotransmitter, and the serotonergic system is one of the best studied and understood transmitter systems. It is crucially involved in the organization of virtually all behaviours and in the regulation of emotion and mood. Alterations in the serotonergic system, induced by e.g. learning or pathological processes, underlie behavioural plasticity and changes in mood, which can finally results in abnormal behaviour and psychiatric conditions. Not surprisingly, the serotonergic system and its functional components appear to be targets for a multitude of pharmacological treatments - examples of very successful drugs targeting the serotoninergic system include Prozac and Zoloft. The last decades of research have not only fundamentally expanded our view on serotonin but also revealed in much more detail an astonishing complexity of this system, which comprises a multitude of receptors and signalling pathways. A detailed view on its role in basal, but also complex, behaviours emerged, and, was presented in a number of single review articles. Although much is known now, the serotonergic system is still a fast growing field of research contributing to our present understanding of the brains function during normal and disturbed behaviour. This handbook aims towards a detailed and comprehensive overview over the many facets of behavioural serotonin research. As such, it will provide the most up to date and thorough reading concerning the serotonergic systems control of behaviour and mood in animals and humans. The goal is to create a systematic overview and first hand reference that can be used by students and scholars alike in the fields of genetics, anatomy, pharmacology, physiology, behavioural neuroscience, pathology, and psychiatry. The chapters in this book will be written by leading scientists in this field. Most of them have already written excellent reviews in their field of expertise. The book is divided in 4 sections. After an historical introduction, illustrating the growth of ideas about serotonin function in behaviour of the last forty years, section A will focus on the functional anatomy of the serotonergic system. Section B provides a review of the neurophysiology of the serotonergic system and its single components. In section C the involvement of serotonin in behavioural organization will be discussed in great detail, while section D deals with the role of serotonin in behavioural pathologies and psychiatric disorders. The first handbook broadly discussing the behavioral neurobiology of the serotonorgic transmitter system Co-edited by one of the pioneers and opinion leaders of the past decades, Barry Jacobs (Princeton), with an international list (10 countries) of highly regarded contributors providing over 50 chapters, and including the leaders in the field in number of articles and citations: K. P. Lesch, T. Sharp, A. Caspi, P. Blier, G.K. Aghajanian, E. C. Azmitia, and others The only integrated and complete resource on the market containing the best information integrating international research, providing a global perspective to an international community Of great value not only for researchers and experts, but also for students and clinicians as a background reference
Front Cover 1
Handbook of the Behavioral Neurobiology of Serotonin 4
Copyright Page 5
Contents 8
Preface 12
List of Contributors 14
Section 1: Functional Anatomy of the Serotonergic System 18
Chapter 1.1 Evolution of Serotonin: Sunlight to Suicide 20
Introduction 20
Tryptophan 21
Serotonin 26
Summary 33
Acknowledgements 34
References 34
Chapter 1.2 Genetic Organization of the Serotonergic System 40
Introduction 40
Subfamilies of 5-HT receptors 41
Tryptophan hydroxylase genes 49
Serotonin transporter gene (SERT, 5-HTT, SLC6A4) 52
Brain-derived neurotrophic factor gene (BDNF) 53
Monoamine oxidase genes (MAO) 54
Conclusions 56
Acknowledgements 56
References 57
Chapter 1.3 The Neuroanatomy of the Serotonergic System 68
Introduction 68
Divisions of the raphe and associated serotonin-containing nuclei 69
Connectivity 71
Conclusions 76
References 76
Chapter 1.4 Ultrastructure of the Serotonin Innervation in the Mammalian Central Nervous System 82
Introduction 82
5-HT cell bodies and dendrites 88
5-HT innervation of the forebrain 88
5-HT innervaton of the brainstem 99
5-HT innervation of the cerebellum 105
5-HT innervation of the spinal cord 105
Concluding remarks 107
Acknowledgements 107
References 107
Chapter 1.5 Classification and Signaling Characteristics of 5-HT Receptors 120
Introduction 120
Historical perspective of 5-HT receptor classification: a ping-pong game between pharmacology and molecular biology 121
Genomic, post-genomic characteristics of 5-HT receptors 123
G protein-mediated signaling 126
Non-G-protein dependent signaling 128
Constitutive activity 129
Agonist-directed signaling 129
Toward the notion of a 5-HT receptor complex 130
5-HT[sub(3)] receptor signaling 133
References 134
Chapter 1.6 Distribution of 5-HT Receptors in the Central Nervous System 140
Introduction 140
5-HT[sub(1A)] receptors 140
5-HT[sub(1B)] receptors 141
5-HT[sub(1D)] receptors 143
5-ht[sub(1E)] receptors 144
5-HT[sub(1F)] receptors 144
5-HT[sub(2A)] receptors 145
5-HT[sub(2B)] receptors 145
5-HT[sub(2C)] receptors 145
5-HT[sub(3)] receptors 146
5-HT[sub(4)] receptors 147
5-ht[sub(5a)] receptors 148
5-HT[sub(6)] receptors 149
5-HT[sub(7)] receptors 149
Conclusion 150
References 150
Chapter 1.7 Measuring Serotonin Activity in vivo in the Brains of Animals and Humans 156
Introduction 156
Measurement of serotonin release (efflux) in vivo 157
Measurement of receptors and transporters in vivo 160
Tryptophan depletion and the measurement of serotonin function 162
Neuroendocrine markers and serotonergic function 163
Measurement of neuronal activity – neural pathways 163
Conclusions 163
Acknowledgements 164
References 164
Section 2: The Neurophysiology of Serotonin 168
Chapter 2.1. Activity of Brain Serotonergic Neurons in Relation to Physiology and Behavior 170
Introduction 170
Basic neuronal characteristics 171
Sleep–wake–arousal cycle 171
Response to stressors 171
Autonomic function 173
Motor activity 174
Fatigue 176
Discussion 177
Acknowledgement 178
References 178
Chapter 2.2. Electrophysiology of Serotonin Receptors 180
Introduction 180
5-HT[sub(1A)] receptors 181
5-HT[sub(1B)] receptors 183
5-HT[sub(1D)] receptors 184
5-HT[sub(1E)] receptors 184
5-HT[sub(1F)] receptors 184
5-HT[sub(2A)] receptors 184
5-HT[sub(1B)] receptors 188
5-HT[sub(2C)] receptors 188
5-HT[sub(3)] receptors 189
5-HT[sub(4)] receptors 191
5-HT[sub(5)] receptors 192
5-HT[sub(6)] receptors 192
5-HT[sub(7)] receptors 192
Summary 193
References 194
Chapter 2.3. Tryptophan Hydroxylase and Serotonin Synthesis Regulation 200
Serotonin biosynthesis 200
Background of tryptophan hydroxylase 201
Tryptophan hydroxylase in behavioral neuroscience 211
Notes 213
References 214
Chapter 2.4. The Degradation of Serotonin: Role of MAO 220
Introduction: pathways of serotonin degradation 220
MAO: general characteristics 221
MAO isoenzymes 222
Transcription and translation of MAO 224
Localization and distribution of MAO 224
Role of MAO in behavioral regulation: pharmacological inhibition 225
Role of MAO in behavioral regulation: human evidence 226
Role of MAO in behavioral regulation: animal evidence 227
Conclusions 229
Acknowledgements 229
References 229
Chapter 2.5. Cellular Effects of Serotonin in the CNS 236
Introduction 236
The hippocampus 237
The cerebral cortex 241
The road ahead 245
Acknowledgements 245
References 246
Chapter 2.6. Serotonergic Feedback Control 250
Introduction 250
5-HT autoreceptors 250
Postsynaptic 5-HT feedback control mechanisms 253
Neural pathways involved in postsynaptic 5-HT feedback 255
Conclusion 259
Acknowledgements 259
References 259
Chapter 2.7. Tryptophan Depletion and Serotonin Release – A Critical Reappraisal 266
Introduction 266
Tryptophan depletion 266
Effects of tryptophan depletion on 5-HT release and neuronal activity 267
Effects of tryptophan depletion on serotonin receptors 269
Other effects of tryptophan depletion – alternative mechanisms 269
Consequences for the interpretation of tryptophan-depletion induced effects 271
Conclusion 272
Acknowledgement 272
References 272
Chapter 2.8. Serotonin Interaction with Other Transmitter Systems 276
Introduction 276
Noradrenaline 277
Dopamine 278
Acetylcholine 283
GABA 283
Glutamate 284
Acknowledgements 286
References 286
Chapter 2.9. Serotonergic Regulation of Rhythmical Activity of the Brain, Concentrating on the Hippocampus 294
Serotonergic systems of the brainstem 294
Serotonergic neurons of the dorsal and median raphe nuclei 295
Ascending projections of the dorsal raphe nucleus 295
Ascending projections of the median raphe nucleus 297
Differential DRN and MRN projections 297
Differential serotonergic DRN and MRN projections to the septum and hippocampus 297
Role of the median raphe (MRN) nucleus in the control of non-theta states of the hippocampal electroencephalogram (EEG) – or hippocampal EEG desynchronization 299
Recent examination of the effects of MRN stimulation on the hippocampal EEG and hippocampal unit activity 299
Unit activity in the median raphe nucleus in relation to the hippocampal EEG – serotonergic and non-serotonergic neurons 300
Site(s) of action of MRN desynchronizing effects on the hippocampal EEG 304
Functional significance of theta and by inference the functional role of MRN-elicited blockade of theta- or the desynchronization (non-theta) of the hippocampal EEG 304
Unit activity in the dorsal raphe nucleus (DRN) in relation to the hippocampal EEG (serotonergic and non-serotonergic neurons) and possible functional roles 305
Acknowledgement 306
References 306
Chapter 2.10. 5-HT Neurons and Central CO[sub(2)] Chemoreception 310
Introduction 310
The 5-HT system stimulates respiratory output 310
The 5-HT system is involved in the response to hypercapnia 311
5-HT neurons have cellular properties consistent with a role as CRCs 312
Respiratory output and chemoreception are altered by interfering with the 5-HT system 313
Role of 5-HT neurons in forebrain effects of hypercapnia 314
The 5-HT system, ventilation and human disease 315
Acknowledgements 318
References 318
Section 3: Serotonin and Behavioral Control 324
Chapter 3.1 Serotonin and Development 326
Development of the serotonergic system 326
Role of serotonin in brain development 328
Environmental effects on the development of serotonin 332
Summary 333
References 334
Chapter 3.2 Serotonin and Basal Sensory–Motor Control 342
Introduction 342
Methodological considerations in brain/behavior analyses 342
Serotonin and motoric function 344
Serotonin and sensory input interactions 345
Serotonin and sensory–motor reactivity 345
References 346
Chapter 3.3 Role of the Serotonergic System in Appetite and Ingestion Control 348
Introduction 348
Serotonin and feeding behavior: early studies with human participants 349
Serotonin and satiety: the role of serotonin receptor subtypes 350
Neural mechanisms underpinning serotonergic modulation of feeding behavior 354
Serotonin and downstream peptidergic mechanisms in the hypothalamus 356
Serotonin–CCK interactions 356
Concluding remarks 358
References 358
Chapter 3.4 Serotonin and Sexual Behavior 364
Introduction 364
Female sexual behavior 365
Male sexual behavior 370
Overall summary and future directions 375
Acknowledgements 376
References 376
Chapter 3.5 Serotonin in Mood and Emotion 384
Introduction 384
Neuroanatomy of emotion 384
Serotonergic innervation of the limbic system 386
Serotonergic modulation of emotion 387
Agents that increase serotonergic neurotransmission 387
Agents that decrease serotonergic neurotransmission 389
Serotonin transporter gene polymorphism and emotional processing 390
Agents acting directly on specific subtypes of serotonin receptor 391
Conclusion 392
Acknowledgements 392
References 392
Chapter 3.6 Serotonin and the Neurobiology of Anxious States 396
Introduction 396
Neural circuits modulating anxiety-related behavior and anxious states 402
Neural circuits modulating vulnerability to panic-like responses 403
Modulation of anxiety-related circuits by serotonin 404
Summary and future directions 407
Acknowledgements 408
References 408
Chapter 3.7 Role of Serotonin in Brain Reward and Regulation of Alcohol Drinking Behavior 416
Introduction 416
ICSS and ICSA studies and the effects of 5-HT 417
Place conditioning and effects of 5-HT 420
Involvement of 5-HT in conditioned reward and delay of reward 422
Involvement of 5-HT in regulation of alcohol drinking behavior in rodent models 425
Summary/conclusions 428
Acknowledgements 428
References 428
Chapter 3.8 Role of Central Serotonin in Impulsivity and Compulsivity: Comparative Studies in Experimental Animals and Humans 432
Introduction 432
5-HT and impulsivity 433
5-HT and compulsivity 440
Conclusions 441
Acknowledgements 442
References 442
Chapter 3.9 Experimental Studies on the Role(s) of Serotonin in Learning and Memory Functions 446
Introduction 446
Exploring the role of serotonin in memory using invertebrate system models 447
Exploring the role of serotonin in memory by alterations of the 5-HT system in higher vertebrates 450
Manipulating other neurotransmitter systems in combination with alterations of 5-HT functions: the cholinergic system as an example 455
General conclusions 459
Acknowledgements of Strasbourg 460
References 460
Chapter 3.10 Social Behavior and Serotonin 466
Introduction 466
Serotonin and aggression 466
Serotonergic candidate genes 467
Serotonin receptors and aggression 467
Serotonin transporter and aggression 468
MAOA and aggression 469
TPH2 and aggression 470
Concluding thoughts 471
Acknowledgement 471
References 471
Chapter 3.11 Serotonin in Pain and Pain Control 474
Introduction 474
Basic physiology of serotonin in pain and pain control 474
Data from human studies 480
Conclusion 483
Acknowledgements 483
References 483
Section 4: Serotonin in Disease Conditions 490
Chapter 4.1 The Impact of Stress on Serotonergic Neurotransmission 492
Introduction 492
Effects of stress on the raphe nuclei: c-Fos expression and neuronal firing 493
Effect of stress on the synthesis of 5-HT 495
Effects of stress on the extracellular levels of 5-HT and 5-hydroxyindoleacetic acid 496
Effects of stress on serotonergic neurotransmission in animal models of aberrant HPA axis functioning 501
Enhanced stress coping by exercise 502
Concluding remarks and future 502
Acknowledgements 503
References 503
Chapter 4.2 The Role of Serotonin in Depression 510
Introduction 510
Serotonin in the etiology of depression 511
Behavioral pharmacology of antidepressant drugs 512
Animal tests and models of depression 512
5-HT system and antidepressant responses 514
Conclusion 517
References 518
Chapter 4.3 The Role of Serotonin in Drug Addiction 524
Introduction 524
Measuring drug addiction in animal models 525
Cocaine 526
Amphetamine 535
Methamphetamine 539
MDMA 540
Morphine and heroin 542
Nicotine 545
Conclusion 547
Acknowledgement 548
References 548
Chapter 4.4 The Serotonergic System in Obsessive-Compulsive Disorder 564
Introduction 564
Pharmacotherapy 564
Pharmacologic challenge studies 566
Receptor binding studies 566
Genetic association studies 569
Animal models 572
Conclusion 574
References 575
Chapter 4.5 The Role of Serotonin in Attention-Deficit Hyperactivity Disorder (ADHD) 582
Introduction 582
Genetics 583
Neurotransmitter activity and functional associations 589
Conclusions 593
References 593
Chapter 4.6 Serotonin and Schizophrenia 602
Introduction 602
History of the serotonin hypothesis of schizophrenia 603
The dopamine hypothesis of schizophrenia 604
Phenomenology of hallucinogenic drug action 605
Animal models of hallucinogen effects relevant to schizophrenia 607
Serotonin receptor and transporter changes in vivo and post-mortem in schizophrenia 608
Genetic association studies regarding schizophrenia and serotonin 612
Serotonergic mechanisms of atypical antipsychotics 614
Serotonergic challenge studies 619
Serotonin metabolites in the cerebrospinal fluid 620
Platelet studies 620
Neurotrophic role of serotonin in the developmental disorder schizophrenia 621
Serotonin–glutamate interactions 622
Conclusions and future directions 623
Acknowledgements 624
References 624
Chapter 4.7 Serotonin and Serotonin Receptors in Hallucinogen Action 638
Introduction 638
Receptors mediating the behavioral effects of hallucinogens in animals 639
Chemistry and structure–activity relationships 642
Receptors mediating the behavioral effects of MDMA in animals 645
Clinical studies of hallucinogens in humans 647
Summary 648
Acknowledgements 649
References 649
Chapter 4.8 The Role of Serotonin in Cortical Development: Implications for Autism Spectrum Disorder 654
Introduction 654
Serotonin in cortical development 655
Serotonin in ASD 659
A conceptual framework for the etiology of ASD behavioral endophenotypes 667
Conclusion 670
References 670
Chapter 4.9 Serotonin in Panic and Anxiety Disorders 684
Introduction 684
5-HT related drugs and the treatment of anxiety disorders 685
How do SSRIs and buspirone work? 686
Are anxiety disorders caused by disturbances in 5-HT-mediated neurotransmission? 686
The dual role of 5-HT in anxiety: the Deakin and Graeff theory 687
Genetic manipulations of the 5-HT system 695
Conclusions 696
References 697
Chapter 4.10 Serotonin and Aggression 704
Introduction 704
The emergence of the serotonin–aggression link 707
Modulation of 5-HT synthesis and aggression 708
5-HT receptors and aggression 710
5-HT transporters (5-HTT) and aggression 714
Monoamine oxidase A (MAOA) and aggression 716
Other molecules that directly or indirectly affect 5-HT pathways and aggression 717
General conclusions 719
References 720
Chapter 4.11 Altered Serotonin Function in Anorexia and Bulimia Nervosa 732
Introduction 732
Clinical symptoms and puzzling behaviors 733
Neurobiology 735
Implications 740
Conclusion 741
References 741
Chapter 4.12 Genetic, Epigenetic and Environmental Factors in Serotonin-Associated Disease Conditions 748
Introduction 748
Genetic, epigenetic and environmental effects that modulate serotonergic neurotransmission 749
Aggression and impulsivity as behavioral manifestations of central serotonergic dysfunction 751
Serotonergic neurotransmission and the response to acute alcohol intake 752
Disposition to excessive alcohol intake: gene–environment interactions 753
Serotonin and major depression 756
Serotonin dysfunction and obsessive-compulsive disorder 758
Summary and outlook 759
Acknowledgements 759
References 759
Chapter 4.13 The Behavioral Genetics of Serotonin: Relevance to Anxiety and Depression 766
Introduction 766
5-HT synthesis, storage, release, uptake and degradation 767
5-HT receptors 779
Summary and concluding remarks 791
Acknowledgement 792
References 792
Chapter 4.14 Functional Pharmacogenetics of Serotonin Receptors in Psychiatric Drug Action 808
Introduction 808
Genetic polymorphisms and pharmacogenetic mechanisms 809
5-HT[sub(1A)] receptor 809
5-HT[sub(2A)] receptor 811
5-HT[sub(2C)] receptor 812
5-HT[sub(1B)] and 5-HT[sub(1D)] receptors 814
5-HT[sub(3)] receptor 815
5-HT[sub(4)] receptor 816
5-HT[sub(6)] receptor 816
5-HT[sub(7)] receptor 816
Summary and synthesis 817
References 818
Index 824
A 824
B 825
D 826
D 826
E 827
F 828
G 828
H 828
I 830
L 831
M 831
N 832
O 832
P 832
R 833
S 833
T 835
V 835
Y 835
Z 835
Color Plates 836
| Erscheint lt. Verlag | 30.12.2009 |
|---|---|
| Sprache | englisch |
| Themenwelt | Geisteswissenschaften ► Psychologie ► Biopsychologie / Neurowissenschaften |
| Medizin / Pharmazie ► Gesundheitsfachberufe | |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie | |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie | |
| Naturwissenschaften ► Biologie ► Humanbiologie | |
| Naturwissenschaften ► Biologie ► Zoologie | |
| ISBN-10 | 0-08-087817-2 / 0080878172 |
| ISBN-13 | 978-0-08-087817-1 / 9780080878171 |
| Haben Sie eine Frage zum Produkt? |
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