Stress-induced enhancement of fear learning: an animal model of posttraumatic stress disorder

Neurosci Biobehav Rev. 2005;29(8):1207-23. doi: 10.1016/j.neubiorev.2005.04.010. Epub 2005 Aug 10.


Fear is an adaptive response that initiates defensive behavior to protect animals and humans from danger. However, anxiety disorders, such as Posttraumatic Stress Disorder (PTSD), can occur when fear is inappropriately regulated. Fear conditioning can be used to study aspects of PTSD, and we have developed a model in which pre-exposure to a stressor of repeated footshock enhances conditional fear responding to a single context-shock pairing. The experiments in this chapter address interpretations of this effect including generalization and summation or fear, inflation, and altered pain sensitivity. The results of these experiments lead to the conclusion that pre-exposure to shock sensitizes conditional fear responding to similar less intense stressors. This sensitization effect resists exposure therapy (extinction) and amnestic (NMDA antagonist) treatment. The pattern predicts why in PTSD patients, mild stressors cause reactions more appropriate for the original traumatic stressor and why new fears are so readily formed in these patients. This model can facilitate the study of neurobiological mechanisms underlying sensitization of responses observed in PTSD.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Analysis of Variance
  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology*
  • Behavior, Animal
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Disease Models, Animal*
  • Electroshock / adverse effects
  • Excitatory Amino Acid Antagonists / pharmacology
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • Fear*
  • Freezing Reaction, Cataleptic / physiology
  • Freezing Reaction, Cataleptic / radiation effects
  • Injections, Intraventricular / methods
  • Male
  • Random Allocation
  • Rats
  • Rats, Long-Evans
  • Stress Disorders, Post-Traumatic / physiopathology*
  • Time Factors


  • Excitatory Amino Acid Antagonists
  • 2-Amino-5-phosphonovalerate