Alterations in prefrontal cortical serotonin and antidepressant-like behavior in a novel C3H/HeJxDBA/2J recombinant inbred mouse strain

Behav Brain Res. 2013 Jan 1;236(1):283-288. doi: 10.1016/j.bbr.2012.08.012. Epub 2012 Aug 29.


In the present study, two genetically related inbred mouse strains selectively bred for high and low fear-sensitized acoustic startle reflex (FSS) were assessed in the forced swim test model of anti-depressant action and central monoamine concentrations in several brain regions were investigated. These mice were generated through backcrossing C3H/HeJ mice on DBA/2J mice, followed by inbreeding for several generations. The high-FSS and low-FSS strains are known to differ in their acquisition and extinction of fear following auditory fear conditioning. Significantly increased concentrations of 5-HT and its metabolite 5-HIAA were observed in the medial prefrontal cortex (mPFC) but not in the hypothalamus, striatum, hippocampus, amygdala, or midbrain of high-FSS mice compared to low-FSS mice. In addition the concentration of DOPAC, the major metabolite of dopamine was also significantly increased in the mPFC. Furthermore, the high-FSS mice displayed significantly higher levels of immobility in the forced swim test but not the tail suspension test in comparison to the low-FSS group. The mPFC is not only important in the regulation of fear extinction, but also a key region of interest in the study of depression and maintenance of depressive-like behaviors. These data implicate serotonergic modulation in the mPFC in the maintenance of antidepressant-like behavior in a highly fearful mouse strain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Behavior, Animal / physiology*
  • Brain / anatomy & histology
  • Chromatography, High Pressure Liquid
  • Data Interpretation, Statistical
  • Depression / genetics*
  • Depression / psychology*
  • Fear / psychology
  • Hindlimb Suspension / psychology
  • Hydroxyindoleacetic Acid / metabolism
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred DBA
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / physiology*
  • Reflex, Startle / genetics
  • Reflex, Startle / physiology
  • Serotonin / metabolism*
  • Serotonin / physiology*
  • Swimming / psychology


  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Hydroxyindoleacetic Acid