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Neurobiol Learn Mem. 2014 Sep;113:3-18. doi: 10.1016/j.nlm.2013.11.014. Epub 2013 Dec 7.

From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and anxiety disorders.

Author information

1
Tufts University Psychology, 490 Boston Avenue, Medford, MA 02155, USA; Massachusetts General Hospital Psychiatry, 149 Thirteenth Street, Charlestown, MA 02129, USA. Electronic address: michael.vanelzakker@gmail.com.
2
Tufts University Psychology, 490 Boston Avenue, Medford, MA 02155, USA; Massachusetts General Hospital Psychiatry, 149 Thirteenth Street, Charlestown, MA 02129, USA.
3
Massachusetts General Hospital Psychiatry, 149 Thirteenth Street, Charlestown, MA 02129, USA.
4
Tufts University Psychology, 490 Boston Avenue, Medford, MA 02155, USA.

Abstract

Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders.

KEYWORDS:

Amygdala; Anxiety; Fear conditioning; Fear extinction; Posttraumatic stress disorder; Prefrontal cortex; Treatment

PMID:
24321650
PMCID:
PMC4156287
DOI:
10.1016/j.nlm.2013.11.014
[Indexed for MEDLINE]
Free PMC Article

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