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Differential regulation of catechol-O-methyltransferase expression in a mouse model of aggression

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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.

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Acknowledgments

We thank Irina Elarova and Shaona Fang for technical support. Supported by NIH grant MH086385 to SDG and EP.

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Authors and Affiliations

  1. Center for Dementia Research, Nathan Kline Institute, New York University Langone Medical Center, New York, NY, USA

    Stephen D. Ginsberg & Shaoli Che

  2. Division of Neurochemistry, Nathan Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA

    Audrey Hashim, Henry W. Sershen & Jan Volavka

  3. Division of Medical Physics, Nathan Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA

    Sang H. Lee

  4. Division of Child Psychiatry, Nathan Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA

    Eva Petkova

  5. Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA

    Stephen D. Ginsberg, Shaoli Che, Robert Cancro, Henry W. Sershen & Jan Volavka

  6. Department of Physiology and Neuroscience, New York University Langone Medical Center, New York, NY, USA

    Stephen D. Ginsberg

  7. Department of Pathology and NYU Cancer Institute, New York University Langone Medical Center, New York, NY, USA

    Jiri Zavadil

  8. Department of Child and Adolescent Psychiatry, New York University Langone Medical Center, New York, NY, USA

    Eva Petkova

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  1. Stephen D. Ginsberg
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Correspondence to Stephen D. Ginsberg.

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Ginsberg, S.D., Che, S., Hashim, A. et al. Differential regulation of catechol-O-methyltransferase expression in a mouse model of aggression. Brain Struct Funct 216, 347–356 (2011). https://doi.org/10.1007/s00429-011-0315-z

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  • DOI: https://doi.org/10.1007/s00429-011-0315-z

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