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Behav Brain Res. 2013 Jan 1;236(1):283-8. doi: 10.1016/j.bbr.2012.08.012. Epub 2012 Aug 29.

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

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  • 1Neuropharmacology Research Group, Department of Pharmacology and Therapeutics, University College Cork, Ireland.


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.

Copyright © 2012 Elsevier B.V. All rights reserved.

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