Possible involvement of histone acetylation in the development of emotional resistance to stress stimuli in mice

Behav Brain Res. 2012 Dec 1;235(2):318-25. doi: 10.1016/j.bbr.2012.08.010. Epub 2012 Aug 16.


Recent reports have implied that aberrant biochemical processes in the brain frequently accompany subtle shifts in the cellular epigenetic profile that might underlie the pathogenic progression of psychiatric disorders. Furthermore, certain antidepressants or mood stabilizers have been reported to have the ability to modulate epigenetic parameters. We previously reported that pretreatment of mice with 5-HT(1A) receptor agonists 24 h before testing suppressed the decrease in emotional behaviors induced by exposure to acute restraint stress. Based on this finding, the aim of the present study was to examine the association between the development of emotional resistance to stress stimuli and the modulation of an epigenetic parameter, particularly histone acetylation. We found that acetylated histone H3 was increased in the hippocampus of mice that had developed resistance to emotional stress by pretreatment with flesinoxan (1 mg/kg, i.p.) 24 h before testing. On the other hand, pretreatment with benzodiazepine anxiolytic diazepam (1 mg/kg, i.p.) did not have similar effects. Interestingly, similar to flesinoxan, the histone deacetylase inhibitor trichostatin A also protected against the emotional changes induced by acute restraint stress, as well as histone H3 acetylation. The present findings suggest that the epigenetic mechanisms of gene regulation may play an important role in the development of emotional resistance to stress stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Analysis of Variance
  • Animals
  • Anti-Anxiety Agents / therapeutic use
  • Diazepam / therapeutic use
  • Disease Models, Animal
  • Drug Administration Schedule
  • Drug Interactions
  • Emotions / drug effects
  • Emotions / physiology*
  • Epigenesis, Genetic / drug effects
  • Epigenesis, Genetic / physiology*
  • Gene Expression Regulation, Enzymologic
  • Histone Deacetylase Inhibitors / therapeutic use
  • Histones / metabolism*
  • Hydroxamic Acids / therapeutic use
  • Male
  • Mice
  • Mice, Inbred ICR
  • Piperazines / pharmacology
  • Stress, Physiological / drug effects
  • Stress, Physiological / physiology*
  • Stress, Psychological / drug therapy
  • Stress, Psychological / etiology
  • Stress, Psychological / metabolism*
  • Stress, Psychological / prevention & control
  • Time Factors


  • Anti-Anxiety Agents
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • Piperazines
  • flesinoxan
  • trichostatin A
  • Diazepam