The Use of Olfactory Fear Conditioning in Rats to Investigate the Efficacy of Posttraumatic Stress Disorder Treatments Público

Abstract

THE USE OF OLFACTORY FEAR CONDITIONING IN RATS
TO INVESTIGATE THE EFFICACY OF
POSTTRAUMATIC STRESS DISORDER TREATMENTS

By
Ebony M. Glover

A cardinal symptom of posttraumatic stress disorder (PTSD) is the presence of intrusive and persistent memories of the traumatic event. Disrupting fear memories in the aftermath of a traumatic experience may be a useful approach for mitigating these symptoms. A major challenge to this approach is a number of inconsistent findings concerning the efficacy of various post-training treatments in disrupting long-term fear memories. In general, investigators using hippocampal-dependent associative fear models found that certain post-training treatments disrupted fear memories. However, investigators using hippocampal-independent models found that post-training treatments had no effect on fear memories. This dissertation project used a rat model of olfactory-mediated fear-potentiated startle to examine the clinical efficacy of two FDA approved drugs, propranolol and rapamycin, as well as a novel extinction procedure that could be implemented in the aftermath of a traumatic event to prevent or remedy PTSD. Experiments were designed to examine the central hypothesis that hippocampal-dependent fear memories are vulnerable to disruption by post-training manipulations, whereas hippocampal-independent memories are not. The major findings of this project are that hippocampal-independent forms of Pavlovian fear memories are extremely persistent in the face of various post-training manipulations shown to disrupt hippocampal-dependent fear memories. However, when the conditioning procedure is modified to engage the hippocampus, then Pavlovian fear conditioned memories become susceptible to disruption. In addition, results suggest that while treatments given soon after a traumatic experience may have limited effectiveness, treatments given soon after the retrieval of traumatic memories have clinical promise. The present findings underscore the importance of using diverse animal models in translational research.

Table of Contents

Acknowledgments...ii
Table of Contents...v
List of Figures...vi
Chapter 1: General introduction...1
Chapter 2: Differing effects of electroconvulsive shock on consolidation and reconsolidation of olfactory fear memory...2
Chapter 3: Effects of immediate and delayed extinction on inhibition and recovery of olfactory fear memory...3
Chapter 4: Dose and time-dependent effects of systemic propranolol on consolidation and reconsolidation of delay, trace, and context fear memories...4
Chapter 5: Differing effects of systemic rapamycin on consolidation and reconsolidation of context versus cued fear memories...5
Chapter 6: General discussion...6

About this Dissertation

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School	Laney Graduate School
Department	Psychology
Subfield / Discipline	Neuroscience and Animal Behavior
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Psychology, Psychobiology Biology, Neuroscience
Palabra Clave	fear memory consolidation PTSD propranolol reconsolidation Pavlovian fear conditioning fear-potentiated startle rapamycin electroconvulsive shock
Committee Chair / Thesis Advisor	Davis, Michael A, Emory University
Committee Members	Neill, Darryl B, Emory University Hampton, Robert, Emory University Hamann, Stephan, Emory University Ressler, Kerry, Emory University

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