Inhibition of histone deacetylase in the basolateral amygdala facilitates morphine context-associated memory formation in rats

J Mol Neurosci. 2015 Jan;55(1):269-278. doi: 10.1007/s12031-014-0317-4. Epub 2014 May 15.

Abstract

Histone acetylation/deacetylation is a crucial mechanism in memory formation and drug addiction. There is evidence suggesting that histone H3 acetylation may contribute to the long-term neural and behavioral responses to addictive drugs. In addition, the basolateral amygdala (BLA) is critically involved in the formation of cue-associated memories. However, the behavioral effect of histone deacetylase (HDAC) inhibition in the BLA and the underlying molecular alterations at different phases of morphine-induced conditioned place preference (CPP) has not been investigated. In this study, we measured the expression, extinction, and reinstatement of morphine-induced place preference in rats pretreated with trichostatin A (TSA), an HDAC inhibitor. Intra-BLA pretreatment with TSA significantly enhanced morphine-induced CPP acquisition and expression, facilitated extinction, and reduced reinstatement of morphine-induced CPP. These behavioral changes were associated with a general increase in histone H3 lysine14 (H3K14) acetylation in the BLA together with upregulation of the brain-derived neurophic factor (BDNF) and ΔFosB and CREB activation. Collectively, our findings imply that HDAC inhibition in the BLA promotes some aspects of the memory that develops during conditioning and extinction training. Furthermore, histone H3 acetylation may play a role in learning and memory for morphine addiction in the BLA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / drug effects
  • Amygdala / metabolism*
  • Amygdala / physiology
  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Conditioning, Classical*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism*
  • Histones / metabolism
  • Hydroxamic Acids / pharmacology*
  • Male
  • Memory*
  • Morphine / pharmacology*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • Proto-Oncogene Proteins c-fos
  • trichostatin A
  • Morphine
  • Histone Deacetylases