Systemic or Intrahippocampal Delivery of Histone Deacetylase Inhibitors Facilitates Fear Extinction

K. Matthew Lattal, Ruth M. Barrett, Marcelo A. Wood

Research output: Contribution to journalArticle

187 Scopus citations

Abstract

Several recent studies have shown that chromatin, the DNA-protein complex that packages genomic DNA, has an important function in learning and memory. Dynamic chromatin modification via histone deacetylase (HDAC) inhibitors and histone acetyltransferases may enhance hippocampal synaptic plasticity and hippocampus-dependent memory. Little is known about the effects of HDAC inhibitors on extinction, a learning process through which the ability of a previously conditioned stimulus, such as a conditioning context, to evoke a conditioned response is diminished. The authors demonstrate that administration of the HDAC inhibitors sodium butyrate (NaB) systemically or trichostatin A (TSA) intrahippocampally prior to a brief (3-min) contextual extinction session causes context-evoked fear to decrease to levels observed with a long (24-min) extinction session. These results suggest that HDAC inhibitors may enhance learning during extinction and are consistent with other studies demonstrating a role for the hippocampus in contextual extinction. Molecular and behavioral mechanisms through which this enhanced extinction effect may occur are discussed.

Original languageEnglish (US)
Pages (from-to)1125-1131
Number of pages7
JournalBehavioral Neuroscience
Volume121
Issue number5
DOIs
StatePublished - Oct 1 2007

Keywords

  • extinction
  • fear
  • hippocampus
  • histone acetylation
  • memory

ASJC Scopus subject areas

  • Behavioral Neuroscience

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