The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear

Timothy, Bredy and Barad, Mark (2008) The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear. Learning & Memory, 15 1: 39-45. doi:10.1101/lm.801108


Author Timothy, Bredy
Barad, Mark
Title The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear
Journal name Learning & Memory   Check publisher's open access policy
ISSN 1072-0502
1549-5485
Publication date 2008-01
Year available 2008
Sub-type Article (original research)
DOI 10.1101/lm.801108
Open Access Status DOI
Volume 15
Issue 1
Start page 39
End page 45
Total pages 7
Place of publication Woodbury, NY, United States
Publisher Cold Spring Harbor Laboratory Press
Language eng
Formatted abstract
Histone modifications contribute to the epigenetic regulation of gene expression, a process now recognized to be important for the consolidation of long-term memory. Valproic acid (VPA), used for many years as an anticonvulsant and a mood stabilizer, has effects on learning and memory and enhances the extinction of conditioned fear through its function as a histone deacetylase inhibitor (HDAC). Here we report that VPA enhances long-term memory for both acquisition and extinction of cued-fear. Interestingly, VPA enhances extinction, but also enhances renewal of the original conditioned fear when tested in a within-subjects design. This effect appears to be related to a reconsolidation-like process since a single CS reminder in the presence of VPA can enhance long-term memory for the original fear in the context in which fear conditioning takes place. We also show that by modifying the intertrial interval during extinction training, VPA can strengthen reconsolidation of the original fear memory or enhance long-term memory for extinction such that it becomes independent of context. These findings have important implications for the use of HDAC inhibitors as adjuncts to behavior therapy in the treatment of phobia and related anxiety disorders.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
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Created: Thu, 20 Oct 2011, 16:46:12 EST by Debra McMurtrie on behalf of Queensland Brain Institute