Anxiety and Anxiolytic Drugs (eBook)

Preface 6
List of Contents 11
List of Contributors 13
Learning and Memory 14
1 Introduction 15
2 Behavioural Paradigms for Studying Aversive Memories 16
3 Animal Models 20
4 Neurological Substrates of Aversive Memories 22
5 Cellular Mechanisms Underlying Aversive Learning and Memory 26
6 Clinical Implications 36
References 38
Animal Models of Anxiety 48
1 Introduction 49
2 Tests for Anxiety 51
3 Animal Models 62
4 General Conclusions 72
References 73
Genetic Alterations of the Murine Serotonergic Gene Pathway: The Neurodevelopmental Basis of Anxiety 83
1 Introduction 84
2 Anxiety-Like Behavior in Knockout Mice 85
3 Functional Neuroanatomy of Emotionality: Focus on the Serotonin System 86
4 Clinical Implications and Outlook 113
References 114
Mutagenesis and Knockout Models: Hypothalamic– Pituitary– Adrenocortical System 125
1 Introduction—Understanding Endocrine-Behavior Interactions: Lessons from Mutant Mice 126
2 The Stress Hormone (Hypothalamic–Pituitary–Adrenocortical) System 127
3 Gene Targeting: Promises and Caveats 134
4 Summary 144
References 145
Mutagenesis and Knockout Models: NK1 and Substance P 154
1 Introduction 155
2 An Overview of the Tachykinin System 155
3 Pharmacological Studies 157
4 Generation of Knockout Mice 160
5 Mechanism of Change in Phenotype in Tac1 and NK1R-Null Mutant Mice 168
References 168
Genetic Epidemiology of Anxiety Disorders 174
1 Introduction 175
2 Assessment and Definitions of Anxiety Disorder 175
3 Familial and Genetic Factors 175
4 Review of Family and Twin Studies of Anxiety Disorders in Adults 176
5 Review of Linkage and Association Studies of Anxiety Disorders 177
6 Family Studies and Phenotypic Definitions 179
7 High-Risk Studies of Anxiety Disorders 180
8 Future Directions for Research on Anxiety 181
References 182
Interactions Between Corticotropin-Releasing Hormone and Serotonin: Implications for the Aetiology and Treatment of Anxiety Disorders 191
1 Introduction 192
2 Neuroanatomical Basis for the Interactions Between CRH and Serotonin 194
3 Effects of Central Administration of CRH and Related Peptides on Serotoninergic Neurotransmission 196
4 Interactions Between CRH and Serotonin Under Anxiogenic and Psychologically Stressful Conditions: What CanWe Learn from In Vivo Microdialysis Studies? 199
5 Consequences of Long-Term Changes in the CRH System for Hippocampal Serotoninergic Neurotransmission 206
6 Conclusion 208
References 208
Anxiety Disorders: Noradrenergic Neurotransmission 215
1 Neural Mechanisms of Anxiety and Fear 216
2 Reconsolidation 219
3 Extinction 220
4 The Neurochemical Basis of Fear and Anxiety 222
5 Noradrenergic System 222
6 Posttraumatic Stress Disorder 226
7 Panic Disorder 226
8 Phobic Disorders 227
9 Conclusion 227
References 228
Pathophysiology and Pharmacology of GABAA Receptors 234
1 Inhibitory Interneurons 235
2 Diversity of GABAA Receptors 238
3 Pathophysiology of the GABA System 241
4 Pharmacology of GABAA Receptor Subtypes 244
5 Novel Subtype Selective Benzodiazepine Site Ligands 247
References 249
Excitatory Amino Acid Neurotransmission 257
1 Introduction 258
2 Glutamate Receptors 261
3 Synaptic Plasticity 275
4 Pathophysiology 277
5 Summary 292
References 293
Neurobiology and Treatment of Anxiety: Signal Transduction and Neural Plasticity 312
1 Introduction 313
2 Overview of Anxiety-Induced Signal Transduction and Neural Plasticity 314
3 Cellular Mechanisms of Stress-Induced Structural Plasticity 320
4 Intracellular Signaling Pathways Involved in Fear Memory 321
5 Intracellular Signaling Pathways Involved in Anxiety 327
6 Intracellular Signal Transduction Pathways in the Treatment of Anxiety 328
7 Intracellular Pathways Regulated by Antidepressant Treatment 329
8 Intracellular Pathways Regulated by Benzodiazepines 333
9 Summary and Conclusions 334
References 334
Neuropeptides in Anxiety Modulation 342
1 Neuropeptides 343
2 Anxiety-Related Behaviour 345
3 Neuropeptides Involved in the Regulation of Anxiety-Related Behaviour 347
4 Summary 363
References 364
Neuroendocrine Aspects of PTSD 377
1 Introduction 378
2 Basal HPA Hormone Levels in PTSD 379
3 Glucocorticoid Receptors in PTSD 388
4 Cortisol and ACTH Responses to Neuroendocrine Challenge 389
5 Drawing Conclusions from Challenge Studies: Do They Provide aWindow into the Brain? 397
6 Putative Models of HPA Axis Alterations in PTSD 398
7 Conclusions 403
References 404
Anxiety Disorders: Clinical Presentation and Epidemiology 410
1 Part I: Clinical Presentation 412
2 Part II: Epidemiology 417
3 Summary 431
References 431
Transcultural Issues 438
1 Introduction 438
2 Pharmacogenetics 439
3 Anxiolytic Agents and Ethnic Variations 444
4 Conclusion 449
References 449
Challenge Studies in Anxiety Disorders 453
1 Introduction 454
2 Noradrenergic/Adrenergic Challenges 455
3 Serotonergic Challenges 457
4 Lactate Infusion Challenge 459
5 Cholecystokinin Tetrapeptide Challenge 461
6 Carbon Dioxide 463
7 GABA–Benzodiazepine Receptor Complex 465
8 Conclusion and Outlook 466
References 466
Pharmacotherapy of Anxiety 473
1 Introduction 474
2 Clinical Management of Anxiety 475
3 Anxiolytic Drugs 476
4 Diagnostic Aspects 492
5 Pharmacotherapy of Anxiety Disorders 492
6 Conclusions and Future Directions 498
References 499
New Pharmacological Treatment Approaches for Anxiety Disorders 506
1 Introduction 507
2 Classical Neurotransmitters 508
3 Neuropeptides 512
4 Further Anxiolytic Drug Targets 517
5 Pharmacogenomics and Pharmacoproteomics 521
6 Conclusions 522
References 522
Pharmacogenomics 530
1 Introduction 531
2 Pharmacokinetic Aspects 534
3 Pharmacodynamic Aspects 538
4 The Search for Novel Candidate Genes 541
5 Conclusions 543
References 544
Pharmacoproteomics 550
1 Background 550
2 Proteomics: A New Term for an Old Science 552
3 Proteomics Methods 554
4 Proteomics in Medicine 554
5 Analytical Techniques 555
6 Applications 559
References 562
Subject Index 564