TY - JOUR
T1 - Alterations in prefrontal cortical serotonin and antidepressant-like behavior in a novel C3H/HeJxDBA/2J recombinant inbred mouse strain
AU - Browne, Caroline A.
AU - Clarke, Gerard
AU - Hanke, Joachim
AU - Dinan, Timothy G.
AU - Schwegler, Herbert
AU - Yilmazer-Hanke, Deniz M.
AU - Cryan, John F.
N1 - Funding Information:
John F. Cryan is funded by European Community's Seventh Framework Programme ; grant number: FP7/2007-2013 , grant agreement 201714. The authors acknowledge Ms. Andrea Kröber and Ms. Petra Wendler (Institute of Anatomy, University of Magdeburg/Germany) and Ms. Tara Foley (Department of Anatomy, University College Cork/Ireland) for expert technical assistance. We are thankful to Prof. Peter Wieacker for his support for the generation of mice and valuable comments (Institute of Human Genetics, University of Magdeburg/Germany). The high- and low-FSS mice used in the present study were generated and maintained through funding by the SFB 426-B5 to Herbert Schwegler/Deniz M. Yilmazer-Hanke, Neuroanatomy Section of the Institute of Anatomy, University of Magdeburg/Germany to H. Schwegler, Department of Anatomy, University College Cork/Ireland to D.M. Yilmazer-Hanke (start-up fund, allocation), the MSc in Biotechnology in 2007, University College Cork/Ireland to D.M. Yilmazer-Hanke, and the MeroPharm AG to D.M. Yilmazer-Hanke. The senior authors D.M. Yilmazer-Hanke and J.F. Cryan equally contributed to this work.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbr.2012.08.012
DO - 10.1016/j.bbr.2012.08.012
M3 - Article
C2 - 22960457
AN - SCOPUS:84866547890
VL - 236
SP - 283
EP - 288
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
IS - 1
ER -