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

• Published in: Behavioural brain research 2013-01, Vol.236 (1), p.283-288
• Main Authors: Browne, Caroline A., Clarke, Gerard, Hanke, Joachim, Dinan, Timothy G., Schwegler, Herbert, Yilmazer-Hanke, Deniz M., Cryan, John F.
• Format: Article
• Language: English
• Subjects: 3,4-Dihydroxyphenylacetic Acid - metabolism; Acoustic startle response; Adult and adolescent clinical studies; Amygdala; Animal models; Animals; Antidepressants; Behavior, Animal - physiology; Behavioral psychophysiology; Biological and medical sciences; Brain; Brain - anatomy & histology; C3H/HeJHd; Chromatography, High Pressure Liquid; Cortex (prefrontal); Data Interpretation, Statistical; Data processing; DBA/2J; Depression; Depression - genetics; Depression - psychology; Dopamine; Extinction; Fear - psychology; Fear conditioning; Fear-sensitized acoustic startle reflex (FSS); FST; Fundamental and applied biological sciences. Psychology; Hindlimb Suspension - psychology; Hippocampus; Hydroxyindoleacetic Acid - metabolism; Inbreeding; Medial prefrontal cortex; Medical sciences; Mesencephalon; Metabolites; Mice; Mice, Inbred C3H; Mice, Inbred DBA; monoamines; Mood disorders; Neostriatum; Neuropharmacology; Pharmacology. Drug treatments; Prefrontal Cortex - metabolism; Prefrontal Cortex - physiology; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Psychopharmacology; Reflex, Startle - genetics; Reflex, Startle - physiology; Reflexes; Serotonin; Serotonin - metabolism; Serotonin - physiology; Startle response; Swimming - psychology
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2012.08.012

▸ High and low fear-sensitized acoustic startle reflex strains were selectively bred. ▸ 5-HT concentrations were increased in the mPFC of high-FSS mice. ▸ 5-HIAA concentrations were increased in the mPFC of high-FSS mice. ▸ DOPAC concentrations were increased in the mPFC of high-FSS mice. ▸ High-FSS mice display increased immobility in the FST compared to Low-FSS mice. 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.