Search and Find
Service
Front cover
1
Handbook of Anxiety and Fear
4
Copyright page
5
List of Contributors
6
Preface
10
Acknowledgments
12
Contents
14
Section 1: Introduction
18
Chapter 1.1. Introduction to the handbook on fear and anxiety
20
References
23
Section 2: Animal Models of Anxiety, Fear and Defense
26
Chapter 2.1. Theoretical approaches to the modeling of anxiety in animals
28
I. Introduction
28
II. The nature of anxiety
28
III. The nature of an animal model
32
IV. The nature of a specific test: the elevated plus-maze
35
V. Other animal models of anxiety
38
VI. Models of anxiety and their control by the brain
40
VII. Conclusions
40
References
42
Chapter 2.2. The use of conditioning tasks to model fear and anxiety
46
I. A deceptively simple experiment
47
II. A brief history of Pavlovian fear conditioning
49
III. Behavioral measures of conditional fear
50
IV. Other unconditional stimuli
52
V. Key developments in the neuroanatomy of fear conditioning
53
VI. Pavlovian extinction
55
VII. Individual differences in anxiety disorders
57
VIII. Post-traumatic stress disorder
58
IX. Conclusion
60
Acknowledgment
60
References
60
Chapter 2.3. Extinction of fear: from animal studies to clinical interventions
66
I. Introduction
66
II. Behavioral features of extinction
67
III. Theoretical accounts of extinction
69
IV. Facilitation of extinction by d-cycloserine
69
V. Emerging evidence for multiple mechanisms of extinction
73
VI. Conclusion
76
Acknowledgments
76
References
77
Chapter 2.4. Defensive behaviors, fear, and anxiety
80
I. Fear and anxiety
80
II. Defensive behaviors: what, when, where, and why?
81
III. Relationships to learning
86
IV. Danger learning: conditioning to painful unconditioned stimuli (US)
87
V. Unconditioned and conditioned responses to non-painful stimuli (predators or predator odors)
88
VI. Learning of defense to partial predator stimuli
88
VII. Effects of stress and stress ameliorating conditions on defense
88
VIII. Defense and learning: relationship to anxiety
89
IX. Responses to anxiolytic and panicolytic drugs
89
X. Human defensive behaviors
90
XI. Defensive behavior, fear, and anxiety
93
References
94
Chapter 2.5. Unconditioned models of fear and anxiety
98
I. Introduction
98
II. Models
99
III. Ethological approaches: predator confrontation
103
IV. Conclusions
107
References
110
Section 3: Neural Systems for Anxiety, Fear, and Defense
118
Chapter 3.1. Brain mechanisms of Pavlovian and instrumental aversive conditioning
120
I. Introduction
120
II. Pavlovian fear conditioning
121
III. Aversive instrumental conditioning
126
IV. Using EFF to investigate an aversive ‘‘motive circuit’’
131
V. Summary/conclusions
133
Abbreviations
134
References
134
Chapter 3.2. Neural systems activated in response to predators and partial predator stimuli
142
I. Introduction
142
II. The hypothalamus and its central role in the organization of anti-predator defensive responses
143
III. The medial hypothalamic defensive system
144
IV. Neural inputs to the medial hypothalamic defensive system
145
V. Neural outputs from the medial hypothalamic defensive system
150
VI. Overview of the circuits involved in processing anti-predator defensive responses
152
VII. Neural systems involved in anti-predator contextual conditioning responses
153
References
154
Chapter 3.3. A behavioral and neural systems comparison of unconditioned and conditioned defensive behavior
158
I. Neural system analysis: comparison among models using Pavlovian fear conditioning or predator-related unconditioned and conditioned responses
158
II. Comparisons of use of conditioned and unconditioned animal models of anxiety over time
162
III. Validity of animal models of fear and anxiety
165
Appendix: accessing articles using conditioned and unconditioned models of anxiety
168
References
169
Section 4: The Pharmacology of Anxiety, Fear, and Defense
172
Chapter 4.1. Peptide receptor ligands to treat anxiety disorders
174
I. Introduction
174
II. Neuropeptide systems in anxiety patients
177
III. Anxiety-related behavior and neuropeptides: preclinical evidence
183
IV. Neurochemical evidence linking neuropeptides and the mechanism of action of clinically used anxiolytic drugs
196
V. Many peptide candidates: convergence onto common pathways?
202
VI. Development of small molecule, non-peptide compounds for peptidergic targets
204
VII. Conclusion
212
References
212
Chapter 4.2. Subtype-selective GABAA/benzodiazepine receptor ligands for the treatment of anxiety disorders
240
I. Introduction
240
II. A brief history of anxiolytic development and use
241
III. Benzodiazepines and GABAA receptor heterogeneity
242
IV. Subtype-dependent effects of benzodiazepines: evidence from transgenic mice
244
V. Subtype-dependent effects of benzodiazepines: recent findings with subtype-selective ligands
244
VI. Reducing anxiety selectively: how might this work?
248
VII. Controversies and comments: points of contention between (and within) the ‘‘old’’ and the ‘‘new’’ benzodiazepine pharmacology
253
VIII. Where do we go from here?
254
Acknowledgments
255
References
255
Chapter 4.3. Modulation of anxiety behaviors by 5-HT-interacting drugs
258
I. Introduction
258
II. The serotonin system in the central nervous system
259
III. Human findings: serotonin and pathological anxiety
260
IV.Human findings: experimental studies with patients
261
V. Neuroendocrine studies
262
VI. Human findings: experimental studies with healthy volunteers
263
VII. Human studies: neuroimaging
264
VIII. Summary of clinical studies
265
IX. Serotonin and defensive behavior in animal models
265
X. Dual role of serotonin
268
XI. Serotonin and the hippocampus
271
XII. Genetic manipulations of the 5-HT system
271
XIII.Plasticity of the 5-HT systems and anxiety
274
XIV. Mechanisms of the anxiolytic effects of SSRIs and buspirone
274
XV. Conclusions
276
References
276
Chapter 4.4. The glutamatergic system as a potential therapeutic target for the treatment of anxiety disorders
286
I. Introduction
286
II. Glutamate receptor diversity
287
III. Glutamate receptor structure
288
IV. Advancing glutamate receptor research in anxiety: selective molecules and mutant animals
289
V. Animal models of anxiety
293
VI. Modelling cognitive dysfunction in anxiety
295
VII. Pharmacology of glutamate in animal models of anxiety
295
VIII. NMDA receptors
300
IX. AMPA receptors
302
X. mGluRs
302
XI. Conclusions and future directions
304
References
305
Chapter 4.5. The endocannabinoid system and anxiety responses
320
I. Introduction
320
II. The endocannabinoid system
321
III. Effects of cannabinoids on anxiety
325
IV. Role of the endocannabinoid system in anxiety
327
V. Methodological issues in the study of endocannabinoids in anxiety
329
VI. Mechanisms for the endocannabinoid role in anxiety
330
VII. Endocannabinoids as a pharmacological target for anxiety treatment
332
VIII. Conclusions
333
Acknowledgments
333
References
333
Chapter 4.6. Genetic factors underlying anxiety-behavior: a meta-analysis of rodent studies involving targeted mutations of neurotransmission genes
342
I. Introduction
342
II. Are some particular behavioral tests used in these studies?
343
III. Which genetic method has been used?
360
IV. Was there any particular choice of construction (knock-in, knock-out, and over-expressed models) made for each neurotransmission system?
360
V. Which phenotypes are observed?
361
VI. Can these results be explained by the species or the strain used?
361
VII. Did this strategy enable to precise the brain area involved in these processes?
362
VIII. Is the contribution of the genetic factor limited to the developmental period?
362
IX. Do the effects of the mutation correlate with the results of pharmacological challenge?
362
X. Does the mutation modify the response to anxiolytic or anxiogenic agents?
363
XI. What do these findings tell us about the link between neurotransmitter systems and anxiety? Do these studies provide useful information about the role played by the various GABAergic, serotoninergic, glutamatergic, and neuropeptidergic targets in the anxi
363
XII. Conclusion and perspectives
364
References
365
Chapter 4.7. The pharmacology of anxiolysis
372
I. Introduction
372
II. Recent developments and emerging targets
372
III. Concluding remarks and future directions
376
References
376
Section 5: Handbook of Fear and Anxiety: Clinical and Experimental Considerations
380
Chapter 5.1. Phenomenology of anxiety disorders
382
I. Anxiety disorders: clinical features
382
II. Social anxiety disorder (SAnD)
383
III. Obsessive-compulsive disorder
388
IV. Panic disorder
393
V. Generalized anxiety disorder
398
VI. Post-traumatic stress disorder
402
VII. Conclusions
405
Abbreviations
405
References
405
Chapter 5.2. How effective are current drug treatments for anxiety disorders, and how could they be improved?
412
I. Which pharmacological treatments are efficacious in anxiety disorders?
412
II. What is the mechanism of action in anxiety disorders?
413
III. Do randomised controlled trials reveal consistent differences in efficacy?
415
IV. Why don’t randomised controlled trials reveal more differences between treatments?
415
V. Could clinical outcomes be improved with better use of current treatments?
416
VI. Can psychological therapies enhance the efficacy of pharmacological treatments?
417
VII. Could clinical outcomes be improved, with new targets for anxiolytic drugs?
418
VIII. Could clinical outcomes be improved through using genetic approaches?
419
IX. The insights offered by studies of pharmacological modulation of emotion processing
420
X. Do neuroimaging studies explain the neuroanatomy of the treatment response?
421
References
422
Chapter 5.3. Experimental models: panic and fear
430
I. Introduction
430
II. Sodium lactate and other hyperosmotic infusion techniques
432
III. Carbon dioxide
435
IV. Cholecystokinin
437
V. Voluntary hyperventilation
440
VI. Doxapram
442
VII. Other experimental models of panic
442
VIII. General conclusions
444
Abbreviations
444
References
444
Chapter 5.4. Principles and findings from human imaging of anxiety disorders
454
I. Introduction
454
II. Choice of imaging modality
455
III. Molecular imaging
457
IV. Molecular imaging in anxiety disorders
460
References
467
Chapter 5.5. Stress hormones and anxiety disorders
472
I. Introduction: stress, fear and anxiety
472
II. Anxiety disorders and stressful events: is there a connection? – The role of life events
473
III. Stress response systems: stress and neuroendocrine regulation
474
IV. Links between HPA and noradrenergic function in animal studies
474
V. The SNS in anxiety disorders
482
VI. Summary and conclusions
484
References
485
Chapter 5.6. The genetics of human anxiety disorders
492
I. Introduction
492
II. Genetic epidemiology
492
III. Molecular genetics
501
IV. Functional genetics
512
V. Summary and further directions
513
Abbreviations
514
References
515
Subject Index
528
All prices incl. VAT