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Postreactivation glucocorticoids impair recall of established fear memory.

Abstract
Pavlovian fear conditioning provides one of the best rodent models of acquired anxiety disorders, including posttraumatic stress disorder. Injection of a variety of drugs after training in fear-conditioning paradigms can impair consolidation of fear memories. Indeed, early clinical trials suggest that immediate administration of such drugs after a traumatic event may decrease the risk of developing posttraumatic stress disorder in humans (Pitman et al., 2002; Vaiva et al., 2003). The use of such a treatment is limited by the difficulty of treating every patient at risk and by the difficulty in predicting which patients will experience chronic adverse consequences. Recent clinical trials suggest that administration of glucocorticoids may have a beneficial effect on established posttraumatic stress disorder (Aerni et al., 2004) and specific phobia (Soravia et al., 2006). Conversely, glucocorticoid administration after training is known to enhance memory consolidation (McGaugh and Roozendaal, 2002; Roozendaal, 2002). From a clinical perspective, enhancement of a fear memory or a reactivated fear memory would not be desirable. We report here that when glucocorticoids are administered immediately after reactivation of a contextual fear memory, subsequent recall is significantly diminished. Additional experiments support the interpretation that glucocorticoids not only decrease fear memory retrieval but, in addition, augment consolidation of fear memory extinction rather than decreasing reconsolidation. These findings provide a rodent model for a potential treatment of established acquired anxiety disorders in humans, as suggested by others (Aerni et al., 2004; Schelling et al., 2004), based on a mechanism of enhanced extinction.
AuthorsWen-Hui Cai, Jacqueline Blundell, Jie Han, Robert W Greene, Craig M Powell
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 26 Issue 37 Pg. 9560-6 (Sep 13 2006) ISSN: 1529-2401 [Electronic] United States
PMID16971540 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Glucocorticoids
Topics
  • Animals
  • Anxiety Disorders (drug therapy, metabolism, physiopathology)
  • Brain (drug effects, metabolism)
  • Conditioning, Psychological (drug effects, physiology)
  • Disease Models, Animal
  • Extinction, Psychological (drug effects, physiology)
  • Fear (drug effects, physiology)
  • Glucocorticoids (pharmacology, therapeutic use)
  • Male
  • Memory (drug effects, physiology)
  • Memory Disorders (chemically induced, metabolism, physiopathology)
  • Mice
  • Mice, Inbred C57BL
  • Stress Disorders, Post-Traumatic (drug therapy, metabolism, physiopathology)
  • Stress, Psychological (complications, physiopathology)

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