Translational Methods for PTSD Research

Preface to the Series
Preface: Research Methods for clinical and preclinical post-traumatic stress disorder (PTSD)
References
Contents
Contributors
Chapter 1: Translational Model of Infant PTSD Induction: Methods for Infant Fear Conditioning
1 Introduction
2 Basic Overview of Unique Learning Characteristics of the Three Learning Epochs
2.1 Sensitive Period for Attachment (Postnatal Days (PN)0-9)
2.2 Sensitive Period Non-amygdala Aversion Learning
2.3 Sensitive Period Precocial Amygdala-Dependent Aversion Learning
2.4 Transitional Sensitive Period PN10-15
2.5 Post-Sensitive Period PN16-23 (Weaning Age)
3 Fear Conditioning Basics
4 Pup-Specific Preparations for Fear Conditioning
4.1 Managing a Stress-Free Colony
4.2 Preparing Pups for an Experiment Is Done Within 5 Min from Nest to Conditioning
5 Age-Specific Fear Conditioning Methods
5.1 Young Pup Conditioning Procedure
5.2 Setting Up Odor-Shock Conditioning Program in Noldus Ethovision XT
5.3 Older Pup Conditioning Procedure
6 Maternal Presence During Conditioning
6.1 Anesthetized Mother
6.2 Maternal Odor Delivered via an Olfactometer
7 Testing Using Either a Cue Test or Y-Maze
7.1 Cue-Test
7.2 Y-Maze Test
8 Methods to Induce a PTSD Phenotype That Can Be Uncovered by Fear Conditioning
8.1 Scarcity-Adversity Model of Low Bedding (LB)
8.2 Repeated Fear Conditioning
9 Conclusion
References
Chapter 2: Periadolescent Social Isolation Effects on Extinction of Conditioned Fear
1 Introduction: Early-Life Adversity and Posttraumatic Stress Disorder
2 Materials
2.1 Animals
2.2 Housing Facility and Cages
2.3 Conditioned Fear Behavioral Apparatus
3 Methods
3.1 Pre- and Post-weaning
3.2 Treatment Allocation
3.3 Handling, Weighing, and Cage Cleaning
3.4 Isolation Duration
3.5 Re-socialization
3.6 Blinding and Counterbalancing
3.7 Vaginal Lavage
3.8 Standard Conditioned Fear Extinction Protocol
3.8.1 Habituation and Light Cycle
3.8.2 Fear Conditioning, Extinction, and Test
3.8.3 Behavioral Measure of Fear
4 Conclusions
References
Chapter 3: Using Virtual Reality to Study Fear and Extinction in Children and Adolescents
1 Introduction
2 Equipment, Materials, and Setup
2.1 Participants
2.2 Equipment and Software
2.3 Practice Session
2.4 Stimuli and Timing
2.5 Setup
2.6 Dependent Measures
2.6.1 Subjective Ratings
2.6.2 Physiology
2.6.3 Behavior
3 Data Analysis
4 Troubleshooting
5 Concluding Remarks
References
Chapter 4: Assessing the Role of Sleep in the Regulation of Emotion in PTSD
1 Introduction
1.1 Overview of Sleep Assessment Methods Used in PTSD Research
1.2 Factors That Need to Be Considered When Planning Sleep Studies in PTSD Research
1.2.1 Sleep Environment
1.2.2 First-Night Effect
1.2.3 Sleep Apnea and Other Sleep Disorders
1.2.4 Traumatic Brain Injury (TBI) and Physical Injury
1.2.5 Duration of PTSD, Time Elapsed Since Trauma, and Age of Participants
1.2.6 Overnight Sleep vs. Daytime Nap
1.3 Assessment and Experimental Methods Often Used in Sleep Research in PTSD
1.3.1 Emotional Memory and Fear-Based Behaviors
1.3.2 Experimental Simulation of Exposure and Exposure Therapy
1.3.3 Indices of Autonomic Nervous System (ANS)
1.3.4 Assessments of Hypothalamic-Pituitary-Adrenal (HPA) Axis Function
1.3.5 Measures of Chronotype and Circadian Rhythm
1.3.6 Brain Imaging
2 Methods
2.1 Polysomnography (PSG)
2.1.1 Selection of a PSG System
2.1.2 Ambulatory PSG
2.1.3 Preparation
2.1.4 Placement of Sensors
2.1.5 Initiation of Sleep Recording
2.1.6 Scoring
2.1.7 High-Density EEG (hd-EEG)
2.1.8 Notes: PSG
2.2 Actigraphy
2.2.1 Selection of an Actigraphy System
2.2.2 Preparation
2.2.3 Initiation of Recording
2.2.4 Scoring
2.2.5 Notes: Actigraphy
2.3 Sleep Questionnaires and Diaries
2.3.1 Common Sleep Questionnaires
2.3.2 Questionnaires Designed to Assess Trauma/PTSD-Related Sleep Disturbances
2.3.3 Administration, Scoring, and Interpretation of Sleep Questionnaires
2.3.4 Sleep Diaries
2.3.5 Administration and Scoring of Sleep Diaries
2.3.6 Notes: Sleep Questionnaires and Diaries
2.4 Nightmare Measures
2.4.1 Nightmare Questionnaires and Diaries
2.4.2 Dream Reporting during PSG or in Conjunction with Other Sleep Monitoring
2.5 Methods to Examine Associations Between Sleep and Relevant Psychophysiological Phenomena
2.5.1 Fear Conditioning and Extinction
2.5.2 Nocturnal Heart Rate Variability (HRV)
2.5.3 Cortisol
2.5.4 Chronotype and Circadian Markers
2.5.5 Structural and Functional Brain Imaging
3 Conclusion
References
Chapter 5: Pavlovian Conditioning and Extinction Methods for Studying the Neurobiology of Fear Learning in PTSD
1 Introduction
1.1 Comparison with Other Methods
2 Materials
2.1 Subjects
2.2 General Equipment
2.3 Experimental Room
2.4 Biopac Systems Inc. Modular Instrument System
3 Methods
3.1 Experimental Design, Components, and Structure
3.2 Procedure
3.2.1 Intake and Assessment
3.2.2 Subject Preparation
3.2.3 Conditioning
3.2.4 Extinction
3.2.5 Recall and Renewal
4 Notes
4.1 Timing
4.2 Analysis
4.3 Anticipated Results
5 Conclusions
References
Chapter 6: Reconciling Translational Disparities Between Empirical Approaches to Better Understand PTSD
1 Introduction
1.1 Translational Methods to Study Fear-Related Psychophysiological Features of PTSD
2 Materials
2.1 Participants
2.2 Equipment
2.3 Fear-Potentiated Startle
2.4 Skin Conductance Response
2.5 US-Expectancy and Valence Ratings
3 Methods
3.1 Fear Conditioning, Extinction, and Return of Fear
3.2 Fear-Potentiated Startle
3.3 Skin Conductance Response
3.4 US-Expectancy and Valence Ratings
3.5 Common Elements
3.5.1 Associations Between Measurements and Indices
3.5.2 Relevance to Posttraumatic Stress Disorder (PTSD)
3.6 Paradigmatic Strengths
3.7 Discrepancies/Limitations
3.8 Recommendations/Future Directions
4 Conclusions
References
Chapter 7: An Integrative Model for Endophenotypes Relevant to Posttraumatic Stress Disorder (PTSD): Detailed Methodology for ...
1 Introduction: An Integrative Model for Endophenotypes Relevant to PTSD
1.1 Posttraumatic Stress Disorder (PTSD)
1.2 Biological Relevance of Translational Models
1.3 Inescapable Tail Shock Stress (IS)
1.3.1 History
1.3.2 Overview
1.3.3 Utility and Limitations (Advantages/Disadvantages of IS as a Model of Endophenotypes Relevant to PTSD)
1.4 The Juvenile Social Exploration (JSE) Test for Assessing a Stress-Induced Exaggeration of Anxiety-Like Behavior
1.4.1 History
1.4.2 Overview of IS-Induced JSE Deficits
1.4.3 Utility and Limitations
2 IS/JSE materials
2.1 Animals: Sprague Dawley Rats
2.1.1 Experimental and Control Animals
2.1.2 Juveniles (For Use in JSE)
2.2 Housing Environment
2.3 Behavioral Test Administrators
2.4 Behavioral Assessment Environment (JSE)
2.5 Behavioral Assessment Equipment (JSE)
2.6 Stressor Environment (IS)
2.7 Stressor Equipment (IS)
3 IS/JSE Methods
3.1 Housing
3.2 Acclimation
3.3 Behavioral Assessment (Baseline and Post-IS JSE)
3.3.1 Setup
3.3.2 Transportation
3.3.3 Testing
3.3.4 Scoring
3.3.5 In Brief
3.3.6 Data Analysis
3.4 Stressor Application (IS)
3.4.1 Setup
3.4.2 Transportation
3.4.3 Procedure
3.4.4 In Brief
4 IS/JSE Notes
4.1 General
4.1.1 Ordering Rats
4.1.2 Handling Rats
4.1.3 Timing
4.2 IS
4.2.1 Notes Worth Noting
4.2.2 Common Errors (and Fixes)
4.2.3 Pro Tips
4.3 JSE
4.3.1 Notes Worth Noting
4.3.2 Common Errors (and Fixes)
4.3.3 Pro Tips
References
Chapter 8: Apolipoprotein E Isoform-Related Translational Measures in PTSD Research
1 Introduction
2 Materials
2.1 Animal Model and Stressor Exposure
2.2 Plasma and Tissue Collection
3 Methods
3.1 Oxysterol Measures in Brain Tissue and Plasma
3.1.1 Oxysterol Panel in Cortical Tissue
3.1.2 7-Ketocholesterol Analysis in Liver Tissue and Plasma
3.2 Sterol Analysis in Brain Tissue
3.2.1 Hippocampal Cholesterol Analyses
3.2.2 Sterol Panel in Hippocampal Tissue
3.3 Results from Sterol and Oxysterol Analyses
4 Notes and Conclusion
References
Chapter 9: Stress Immobilization Inducing Fear Extinction Deficits in Male and Female Mice
1 Introduction
2 Equipment Materials and Setup
2.1 Mice
2.2 Stress Immobilization Boards
2.3 Vaginal Cytology
2.4 Cued-Fear Conditioning and Fear Extinction
3 Methods
3.1 Stress Immobilization Procedure
3.2 Vaginal Cytology
3.3 Cued-Fear Conditioning and Fear Extinction Procedures
4 Data Analysis
5 Troubleshooting
6 Concluding Remarks
References
Chapter 10: 5-HT Neural System Abnormalities in PTSD Model Rats
1 Introduction
2 Materials
2.1 Animals
2.2 Aversive Stress During Early Postnatal Periods
2.3 Contextual Fear Conditioning Test
2.4 Extinction of Contextual Fear Conditioning
2.5 Surgery for Microinjection
2.6 Drug Administration for Contextual Fear Conditioning
2.7 Drug Administration for Extinction of Contextual Fear Conditioning
3 Results
3.1 Effects of 3WFS on the Anxiolytic Effect of 8-OH-DPAT Systemic Administration
3.2 Effects of 3WFS on the Anxiolytic Effect of 8-OH-DPAT Local Injection into the Brain [12]
3.3 Effects of Early Postnatal Stress on Freezing Behavior During Extinction
3.4 Effects of DCS on Freezing Behavior During Extinction in 3WFS Rats
3.5 Effects of Escitalopram, an SSRI, on Freezing Behavior During Extinction in 3WFS Rats
3.6 Effects of Tandospirone and Diazepam on Freezing Behavior During Extinction in 3WFS Rats
4 Conclusion
References
Chapter 11: Animal Models of PTSD: The Role of Fear Conditioning
1 Introduction: Animals Models for the Study of PTSD
2 Role of Fear Conditioning in PTSD
3 Methods
3.1 Fear Conditioning Models of PTSD
3.2 Traumatic Stress Procedure
3.3 Scoring of Freezing Behavior as a Conditioned Response
3.4 Behavioral Test Batteries
3.5 Main Behavioral and Physiological Changes Observed in Fear Conditioning Models of PTSD
3.6 Sex Differences in the Response to PTSD Animal Models
4 Concluding Remarks
References
Chapter 12: Combining Virtual Reality Exposure Therapy with Non-invasive Brain Stimulation for the Treatment of Post-traumatic...
1 Introduction
2 Basic Mechanisms of Action of NIBS
3 An Overview of the Therapeutic Effectiveness of VRET and NIBS
4 Combining VRET and NIBS in PTSD Treatment
5 Overview of the Available Studies Combining NIBS and VRET in PTSD-Related Syndromes
6 Discussion and Future Directions
7 Conclusion and Perspectives
References
Chapter 13: Associating Aversive Task Exposure with Pharmacological Intervention to Model Traumatic Memories in Laboratory Rod...
Abbreviations
1 Introduction
2 Models and Protocols to Study Fear Memory Processing in Preclinical Research
Box 1: An Overview of Fear Conditioning and Avoidance Tasks on Studying Aversive Memories
3 PTSD as a Memory-Related Psychiatric Disorder
4 PTSD Features Correlated with Memory Overconsolidation
5 The Challenge of Modeling Complex Conditions Like PTSD
6 Neural Basis and Neurochemical Signatures of PTSD Related to Memory Processing
Box 2: Further Reading on the Neural Abnormalities Described in PTSD
Box 3: Further Reading on the Neurochemical Dysfunctions Described in PTSD
7 Potentiating Effects of Post-acquisition Interventions on Aversive Memory Strength
8 Detrimental Effects of Post-acquisition Interventions on Aversive Memory Specificity, Destabilization, Drug-Induced Reconsol...
9 General Discussion
10 Concluding Remarks
References
Chapter 14: Loudness Dependence of Auditory Evoked Potentials: A Promising Pre-treatment Predictor of Selective Serotonin Reup...
Abbreviations
1 Introduction
1.1 LDAEP and Serotonergic Transmission
2 Equipment
3 Methods
3.1 Overview and Description of the LDAEP Task
3.2 Procedures
4 Notes
References
Chapter 15: Preclinical Methods of Neurosteroid-Induced Facilitation of Fear Extinction and Fear Extinction Retention
1 Introduction
2 Role of the GABAA Receptor and GABA Levels in PTSD
3 Role of GABAergic Neurosteroids in PTSD
4 Studying Fear Extinction in Animal Models of PTSD
4.1 The Social Isolation Model and Impairment of GABAergic Signal Transduction
4.1.1 Fear Conditioning Responses, Fear Extinction, and Fear Extinction Retention in the socially isolated Mouse Paradigm
4.1.2 Behavioral Responses of Contextual Fear Conditioning in SI Mice
4.1.3 Fear Paradigm in SI Mice and Role of Allopregnanolone
5 Pharmacological Blockade of Reconsolidation Processes Using Neurosteroid-Based Molecules
6 Reconsolidation Blockade and Fear Extinction in Humans
7 Conclusions and Future Directions
References
Index