Handbook of Anxiety and Fear

Front cover

Handbook of Anxiety and Fear

Copyright page

List of Contributors

Preface

Acknowledgments

Contents

Section 1: Introduction

Chapter 1.1. Introduction to the handbook on fear and anxiety

References

Section 2: Animal Models of Anxiety, Fear and Defense

Chapter 2.1. Theoretical approaches to the modeling of anxiety in animals

I. Introduction

II. The nature of anxiety

III. The nature of an animal model

IV. The nature of a specific test: the elevated plus-maze

V. Other animal models of anxiety

VI. Models of anxiety and their control by the brain

VII. Conclusions

References

Chapter 2.2. The use of conditioning tasks to model fear and anxiety

I. A deceptively simple experiment

II. A brief history of Pavlovian fear conditioning

III. Behavioral measures of conditional fear

IV. Other unconditional stimuli

V. Key developments in the neuroanatomy of fear conditioning

VI. Pavlovian extinction

VII. Individual differences in anxiety disorders

VIII. Post-traumatic stress disorder

IX. Conclusion

Acknowledgment

References

Chapter 2.3. Extinction of fear: from animal studies to clinical interventions

I. Introduction

II. Behavioral features of extinction

III. Theoretical accounts of extinction

IV. Facilitation of extinction by d-cycloserine

V. Emerging evidence for multiple mechanisms of extinction

VI. Conclusion

Acknowledgments

References

Chapter 2.4. Defensive behaviors, fear, and anxiety

I. Fear and anxiety

II. Defensive behaviors: what, when, where, and why?

III. Relationships to learning

IV. Danger learning: conditioning to painful unconditioned stimuli (US)

V. Unconditioned and conditioned responses to non-painful stimuli (predators or predator odors)

VI. Learning of defense to partial predator stimuli

VII. Effects of stress and stress ameliorating conditions on defense

VIII. Defense and learning: relationship to anxiety

IX. Responses to anxiolytic and panicolytic drugs

X. Human defensive behaviors

XI. Defensive behavior, fear, and anxiety

References

Chapter 2.5. Unconditioned models of fear and anxiety

I. Introduction

II. Models

III. Ethological approaches: predator confrontation

IV. Conclusions

References

Section 3: Neural Systems for Anxiety, Fear, and Defense

Chapter 3.1. Brain mechanisms of Pavlovian and instrumental aversive conditioning

I. Introduction

II. Pavlovian fear conditioning

III. Aversive instrumental conditioning

IV. Using EFF to investigate an aversive ‘‘motive circuit’’

V. Summary/conclusions

Abbreviations

References

Chapter 3.2. Neural systems activated in response to predators and partial predator stimuli

I. Introduction

II. The hypothalamus and its central role in the organization of anti-predator defensive responses

III. The medial hypothalamic defensive system

IV. Neural inputs to the medial hypothalamic defensive system

V. Neural outputs from the medial hypothalamic defensive system

VI. Overview of the circuits involved in processing anti-predator defensive responses

VII. Neural systems involved in anti-predator contextual conditioning responses

References

Chapter 3.3. A behavioral and neural systems comparison of unconditioned and conditioned defensive behavior

I. Neural system analysis: comparison among models using Pavlovian fear conditioning or predator-related unconditioned and conditioned responses

II. Comparisons of use of conditioned and unconditioned animal models of anxiety over time

III. Validity of animal models of fear and anxiety

Appendix: accessing articles using conditioned and unconditioned models of anxiety

References

Section 4: The Pharmacology of Anxiety, Fear, and Defense

Chapter 4.1. Peptide receptor ligands to treat anxiety disorders

I. Introduction

II. Neuropeptide systems in anxiety patients

III. Anxiety-related behavior and neuropeptides: preclinical evidence

IV. Neurochemical evidence linking neuropeptides and the mechanism of action of clinically used anxiolytic drugs

V. Many peptide candidates: convergence onto common pathways?

VI. Development of small molecule, non-peptide compounds for peptidergic targets

VII. Conclusion

References

Chapter 4.2. Subtype-selective GABAA/benzodiazepine receptor ligands for the treatment of anxiety disorders

I. Introduction

II. A brief history of anxiolytic development and use

III. Benzodiazepines and GABAA receptor heterogeneity

IV. Subtype-dependent effects of benzodiazepines: evidence from transgenic mice

V. Subtype-dependent effects of benzodiazepines: recent findings with subtype-selective ligands

VI. Reducing anxiety selectively: how might this work?

VII. Controversies and comments: points of contention between (and within) the ‘‘old’’ and the ‘‘new’’ benzodiazepine pharmacology

VIII. Where do we go from here?

Acknowledgments

References

Chapter 4.3. Modulation of anxiety behaviors by 5-HT-interacting drugs

I. Introduction

II. The serotonin system in the central nervous system

III. Human findings: serotonin and pathological anxiety

IV.Human findings: experimental studies with patients

V. Neuroendocrine studies

VI. Human findings: experimental studies with healthy volunteers

VII. Human studies: neuroimaging

VIII. Summary of clinical studies

IX. Serotonin and defensive behavior in animal models

X. Dual role of serotonin

XI. Serotonin and the hippocampus

XII. Genetic manipulations of the 5-HT system

XIII.Plasticity of the 5-HT systems and anxiety

XIV. Mechanisms of the anxiolytic effects of SSRIs and buspirone

XV. Conclusions

References

Chapter 4.4. The glutamatergic system as a potential therapeutic target for the treatment of anxiety disorders

I. Introduction

II. Glutamate receptor diversity

III. Glutamate receptor structure

IV. Advancing glutamate receptor research in anxiety: selective molecules and mutant animals

V. Animal models of anxiety

VI. Modelling cognitive dysfunction in anxiety

VII. Pharmacology of glutamate in animal models of anxiety

VIII. NMDA receptors

IX. AMPA receptors

X. mGluRs

XI. Conclusions and future directions

References

Chapter 4.5. The endocannabinoid system and anxiety responses

I. Introduction

II. The endocannabinoid system

III. Effects of cannabinoids on anxiety

IV. Role of the endocannabinoid system in anxiety

V. Methodological issues in the study of endocannabinoids in anxiety

VI. Mechanisms for the endocannabinoid role in anxiety

VII. Endocannabinoids as a pharmacological target for anxiety treatment

VIII. Conclusions

Acknowledgments

References

Chapter 4.6. Genetic factors underlying anxiety-behavior: a meta-analysis of rodent studies involving targeted mutations of neurotransmission genes

I. Introduction

II. Are some particular behavioral tests used in these studies?

III. Which genetic method has been used?

IV. Was there any particular choice of construction (knock-in, knock-out, and over-expressed models) made for each neurotransmission system?

V. Which phenotypes are observed?

VI. Can these results be explained by the species or the strain used?

VII. Did this strategy enable to precise the brain area involved in these processes?

VIII. Is the contribution of the genetic factor limited to the developmental period?

IX. Do the effects of the mutation correlate with the results of pharmacological challenge?

X. Does the mutation modify the response to anxiolytic or anxiogenic agents?

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

XII. Conclusion and perspectives

References

Chapter 4.7. The pharmacology of anxiolysis

I. Introduction

II. Recent developments and emerging targets

III. Concluding remarks and future directions

References

Section 5: Handbook of Fear and Anxiety: Clinical and Experimental Considerations

Chapter 5.1. Phenomenology of anxiety disorders

I. Anxiety disorders: clinical features

II. Social anxiety disorder (SAnD)

III. Obsessive-compulsive disorder

IV. Panic disorder

V. Generalized anxiety disorder

VI. Post-traumatic stress disorder

VII. Conclusions

Abbreviations

References

Chapter 5.2. How effective are current drug treatments for anxiety disorders, and how could they be improved?

I. Which pharmacological treatments are efficacious in anxiety disorders?

II. What is the mechanism of action in anxiety disorders?

III. Do randomised controlled trials reveal consistent differences in efficacy?

IV. Why don’t randomised controlled trials reveal more differences between treatments?

V. Could clinical outcomes be improved with better use of current treatments?

VI. Can psychological therapies enhance the efficacy of pharmacological treatments?

VII. Could clinical outcomes be improved, with new targets for anxiolytic drugs?

VIII. Could clinical outcomes be improved through using genetic approaches?

IX. The insights offered by studies of pharmacological modulation of emotion processing

X. Do neuroimaging studies explain the neuroanatomy of the treatment response?

References

Chapter 5.3. Experimental models: panic and fear

I. Introduction

II. Sodium lactate and other hyperosmotic infusion techniques

III. Carbon dioxide

IV. Cholecystokinin

V. Voluntary hyperventilation

VI. Doxapram

VII. Other experimental models of panic

VIII. General conclusions

Abbreviations

References

Chapter 5.4. Principles and findings from human imaging of anxiety disorders

I. Introduction

II. Choice of imaging modality

III. Molecular imaging

IV. Molecular imaging in anxiety disorders

References

Chapter 5.5. Stress hormones and anxiety disorders

I. Introduction: stress, fear and anxiety

II. Anxiety disorders and stressful events: is there a connection? – The role of life events

III. Stress response systems: stress and neuroendocrine regulation

IV. Links between HPA and noradrenergic function in animal studies

V. The SNS in anxiety disorders

VI. Summary and conclusions

References

Chapter 5.6. The genetics of human anxiety disorders

I. Introduction

II. Genetic epidemiology

III. Molecular genetics

IV. Functional genetics

V. Summary and further directions

Abbreviations

References

Subject Index