5-HT1A receptor gene silencers Freud-1 and Freud-2 are differently expressed in the brain of rats with genetically determined high level of fear-induced aggression or its absence

Behav Brain Res. 2016 Sep 1:310:20-5. doi: 10.1016/j.bbr.2016.04.050. Epub 2016 May 2.

Abstract

Serotonin 5-HT1A receptor is known to play a crucial role in the mechanisms of genetically defined aggression. In its turn, 5-HT1A receptor functional state is under control of multiple factors. Among others, transcriptional factors Freud-1 and Freud-2 are known to be involved in the repression of 5-HT1A receptor gene expression. However, implication of these factors in the regulation of behavior is unclear. Here, we investigated the expression of 5-HT1A receptor and silencers Freud-1 and Freud-2 in the brain of rats selectively bred for 85 generations for either high level of fear-induced aggression or its absence. It was shown that Freud-1 and Freud-2 levels were different in aggressive and nonaggressive animals. Freud-1 protein level was decreased in the hippocampus, whereas Freud-2 protein level was increased in the frontal cortex of highly aggressive rats. There no differences in 5-HT1A receptor gene expression were found in the brains of highly aggressive and nonaggressive rats. However, 5-HT1A receptor protein level was decreased in the midbrain and increased in the hippocampus of highly aggressive rats. These data showed the involvement of Freud-1 and Freud-2 in the regulation of genetically defined fear-induced aggression. However, these silencers do not affect transcription of the 5-HT1A receptor gene in the investigated rats. Our data indicate the implication of posttranscriptional rather than transcriptional regulation of 5-HT1A receptor functional state in the mechanisms of genetically determined aggressive behavior. On the other hand, the implication of other transcriptional regulators for 5-HT1A receptor gene in the mechanisms of genetically defined aggression could be suggested.

Keywords: 5-HT(1A) receptor; 5-HT(1A) receptor gene silencers Freud-1 and Freud-2; Aggression; Gene expression; Protein level; Rats.

Publication types

  • Comparative Study

MeSH terms

  • Aggression / physiology*
  • Animals
  • Blotting, Western
  • Brain / metabolism*
  • Fear / physiology*
  • Gene Expression Regulation / physiology
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Repressor Proteins / metabolism*
  • Species Specificity

Substances

  • Cc2d1a protein, rat
  • Cc2d1b protein, rat
  • RNA, Messenger
  • Repressor Proteins
  • Receptor, Serotonin, 5-HT1A