Effect of 5-aza-2-deoxycytidine microinjecting into hippocampus and prelimbic cortex on acquisition and retrieval of cocaine-induced place preference in C57BL/6 mice

Eur J Pharmacol. 2010 Sep 10;642(1-3):93-8. doi: 10.1016/j.ejphar.2010.05.050. Epub 2010 Jun 12.


The long lasting addiction-related abnormal memory is one of the most important foundations for relapse. DNA methylation may be a possible mechanism for persistence of such memory. Here we injected the DNA methyltransferases (DNMTs) inhibitor, 5-aza-2-deoxycytidine (5-aza) into hippocampus CA1 area and prelimbic cortex during the stages of acquisition and expression of cocaine-induced place preference in C57BL/6 mice. Results showed that in CA1 DNA methylation inhibitors could restrain acquisition but had no impact on expression of the cocaine-induced conditioned place preference (CPP). On the contrary, in prelimbic cortex, 5-aza had no effect on acquisition but blocked expression. Our results indicated that DNA methylation in hippocampus is required for learning; while DNA methylation in prelimbic cortex is necessary for memory retrieval. The present finding is consistent with the role of the hippocampus as a structure contributing to cocaine-induced memory acquisition, and prelimbic cortex, a part of prefrontal cortex as an area responsible for cocaine-induced memory retrieval. In conclusion, DNA methylation does play an important role in drug-induced learning and memory although the detailed effect still calls for further research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azacitidine / administration & dosage
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Behavior, Animal / drug effects*
  • Catheterization
  • Cocaine / pharmacology*
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors
  • DNA Methylation / drug effects
  • Decitabine
  • Enzyme Inhibitors / pharmacology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Male
  • Memory / drug effects
  • Memory / physiology
  • Mice
  • Mice, Inbred C57BL
  • Microinjections*
  • Substance-Related Disorders / metabolism
  • Substance-Related Disorders / physiopathology


  • Enzyme Inhibitors
  • Decitabine
  • DNA (Cytosine-5-)-Methyltransferases
  • Cocaine
  • Azacitidine