title: Alterations in prefrontal cortical serotonin and antidepressant-like behavior in a novel C3H/HeJxDBA/2J recombinant inbred mouse strain.
abstract: 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.
authors.affiliation: Neuropharmacology Research Group, Department of Pharmacology and Therapeutics, University College Cork, Ireland.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Browne
authors.affiliation: Department of Psychiatry, University College Cork, Cork, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Ireland.
authors.forename: Gerard
authors.initials: G
authors.lastname: Clarke
authors.affiliation: Institut für Anatomie, Medizinische Fakultät, Otto-von-Guerike Universität, Magdeburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Hanke
authors.affiliation: Department of Psychiatry, University College Cork, Cork, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Ireland.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Dinan
authors.affiliation: Institut für Anatomie, Medizinische Fakultät, Otto-von-Guerike Universität, Magdeburg, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwegler
authors.affiliation: Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland. Electronic address: denizyilmazer-hanke@creighton.edu.
authors.forename: Deniz M
authors.initials: DM
authors.lastname: Yilmazer-Hanke
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland. Electronic address: j.cryan@ucc.ie.
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000033:anatomy & histology; D002851:Chromatography, High Pressure Liquid; D003627:Data Interpretation, Statistical; D003863:Depression / Q000235:genetics* / Q000523:psychology*; D005239:Fear / Q000523:psychology; D019417:Hindlimb Suspension / Q000523:psychology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000502:physiology*; D013216:Reflex, Startle / Q000235:genetics / Q000502:physiology; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology*; D013550:Swimming / Q000523:psychology
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid