title: Differential regulation of catechol-O-methyltransferase expression in a mouse model of aggression.
abstract: This study was designed to understand molecular and cellular mechanisms underlying aggressive behaviors in mice exposed to repeated interactions in their homecage with conspecifics. A resident-intruder procedure was employed whereby two males were allowed to interact for 10 min trials, and aggressive and/or submissive behaviors (e.g., degree of attacking, biting, chasing, grooming, rearing, or upright posture) were assessed. Following 10 days of behavioral trials, brains were removed and dissected into specific regions including the cerebellum, frontal cortex, hippocampus, midbrain, pons, and striatum. Gene expression analysis was performed using real-time quantitative polymerase-chain reaction (qPCR) for catechol-O-methyltransferase (COMT) and tyrosine hydroxylase (TH). Compared to naive control mice, significant up regulation of COMT expression of residents was observed in the cerebellum, frontal cortex, hippocampus, midbrain, and striatum; in all of these brain regions the COMT expression of residents was also significantly higher than that of intruders. The intruders also had a significant down regulation (compared to naive control mice) within the hippocampus, indicating a selective decrease in COMT expression in the hippocampus of submissive subjects. Immunoblot analysis confirmed COMT up regulation in the midbrain and hippocampus of residents and down regulation in intruders. qPCR analysis of TH expression indicated significant up regulation in the midbrain of residents and concomitant down regulation in intruders. These findings implicate regionally- and behaviorally-specific regulation of COMT and TH expression in aggressive and submissive behaviors. Additional molecular and cellular characterization of COMT, TH, and other potential targets is warranted within this animal model of aggression.
authors.affiliation: Center for Dementia Research, Nathan Kline Institute, New York University Langone Medical Center, New York, NY, USA. ginsberg@nki.rfmh.org
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Ginsberg
authors.forename: Shaoli
authors.initials: S
authors.lastname: Che
authors.forename: Audrey
authors.initials: A
authors.lastname: Hashim
authors.forename: Jiri
authors.initials: J
authors.lastname: Zavadil
authors.forename: Robert
authors.initials: R
authors.lastname: Cancro
authors.forename: Sang H
authors.initials: SH
authors.lastname: Lee
authors.forename: Eva
authors.initials: E
authors.lastname: Petkova
authors.forename: Henry W
authors.initials: HW
authors.lastname: Sershen
authors.forename: Jan
authors.initials: J
authors.lastname: Volavka
mesh_terms: D000374:Aggression / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D012930:Social Dominance; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D014446:Tyrosine 3-Monooxygenase; D002394:Catechol O-Methyltransferase