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Neurobiol Learn Mem. 2011 May;95(4):453-60. doi: 10.1016/j.nlm.2011.02.006. Epub 2011 Feb 17.

Block of glucocorticoid synthesis during re-activation inhibits extinction of an established fear memory.

Author information

1
Department of Psychology, Memorial University of Newfoundland, 232 Elizabeth Ave., St. John's, Newfoundland A1B3X9, Canada. jblundell@mun.ca

Abstract

BACKGROUND:

The pharmacology of traumatic memory extinction has not been fully characterized despite its potential as a therapeutic target for established, acquired anxiety disorders, including post-traumatic stress disorder (PTSD). Here we examine the role of endogenous glucocorticoids in traumatic memory extinction.

METHODS:

Male C57BL/6J mice were injected with corticosterone (10 mg/kg, i.p.) or metyrapone (50 mg/kg, s.c.) during re-activation of a contextual fear memory, and compared to vehicle groups (N=10-12 per group). To ensure that metyrapone was blocking corticosterone synthesis, we measured corticosterone levels following re-activation of a fear memory in metyrapone- and vehicle-treated animals.

RESULTS:

Corticosterone administration following extinction trials caused a long-lasting inhibition of the original fear memory trace. In contrast, blockade of corticosteroid synthesis with metyrapone prior to extinction trials enhanced retrieval and prevented extinction of context-dependent fear responses in mice. Further behavioral analysis suggested that the metyrapone enhancement of retrieval and prevention of extinction were not due to non-specific alterations in locomotor or anxiety-like behavior. In addition, the inhibition of extinction by metyrapone was rescued by exogenous administration of corticosterone following extinction trials. Finally, we confirmed that the rise in corticosterone during re-activation of a contextual fear memory was blocked by metyrapone.

CONCLUSIONS:

We demonstrate that extinction of a classical contextual fear memory is dependent on endogenous glucocorticoid synthesis during re-activation of a fear memory. Our data suggest that decreased glucocorticoids during fear memory re-activation may contribute to the inability to extinguish a fear memory, thus contributing to one of the core symptoms of PTSD.

PMID:
21333745
PMCID:
PMC3356929
DOI:
10.1016/j.nlm.2011.02.006
[Indexed for MEDLINE]
Free PMC Article

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