Browne, CA,Clarke, G,Hanke, J,Dinan, TG,Schwegler, H,Yilmazer-Hanke, DM,Cryan, JF

2013

January

Behavioural Brain Research

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

Validated

()

Depression Medial prefrontal cortex Serotonin DBA/2J C3H/HeJHd FST Fear-sensitized acoustic startle reflex (FSS) ANTERIOR CINGULATE CORTEX DEPRESSION-RELATED BEHAVIOR ANXIETY-RELATED BEHAVIOR DEEP BRAIN-STIMULATION TAIL SUSPENSION TEST MAJOR DEPRESSION FEAR EXTINCTION BASOLATERAL AMYGDALA COGNITIVE-BEHAVIOR GLUCOSE-METABOLISM

236

283

288

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. (C) 2012 Elsevier B.V. All rights reserved.

DOI 10.1016/j.bbr.2012.08.012