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Catechol- O -methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior
Open accessAbstract
Catechol- O -methyltransferase (COMT) is one of the major mammalian enzymes involved in the metabolic degradation of catecholamines and is considered a candidate for several psychiatric disorders and symptoms, including the psychopathology associated with the 22q11 microdeletion syndrome. By means of homologous recombination in embryonic stem cells, a strain of mice in which the gene encoding the COMT enzyme has been disrupted was produced. The basal concentrations of brain catecholamines were measured in the striatum, frontal cortex, and hypothalamus of adult male and female mutants. Locomotor activity, anxiety-like behaviors, sensorimotor gating, and aggressive behavior also were analyzed. Mutant mice demonstrated sexually dimorphic and region-specific changes of dopamine levels, notably in the frontal cortex. In addition, homozygous COMT-deficient female (but not male) mice displayed impairment in emotional reactivity in the dark/light exploratory model of anxiety. Furthermore, heterozygous COMT-deficient male mice exhibited increased aggressive behavior. Our results provide conclusive evidence for an important sex- and region-specific contribution of COMT in the maintenance of steady-state levels of catecholamines in the brain and suggest a role for COMT in some aspects of emotional and social behavior in mice.
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“The role of COMT in aggression was initially supported by observations of hostility in mice deficient in Comt and the negative correlation between COMT levels and hostility in men with behavioral problems as children [57, 58]; reviewed in Qayyum et al. (2015) [59].”
From Genetics of child aggression, a systematic review (2024) · cites this paper as [57]
In the citing paper
“When early life stress is not taken into account, however, the findings on the relationship between MAOA or COMT and aggression or alcohol use are mixed (Gogos et al. 1998; Bortolato et al. 2011; Ficks And Waldman 2014; Qayyum et al. 2015; Lovallo et al. 2019; Godar et al. 2019; Kaya et al. 2021).”
From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Gogos et al. 1998
In the citing paper
“This is consistent with evidence that COMTVal158Met is differentially expressed across genders (Dempster et al, 2006; Gogos et al, 1998).”
From DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls (2010) · cites this paper as Gogos et al, 1998
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Metadata
- Authors
- Gogos, J. A., Morgan, M., Luine, V., Santha, M., Ogawa, S., Pfaff, D., & Karayiorgou, M.
- Affiliations
- Hunter College (US)
- City University of New York (US)
- The Rockefeller University, New York, NY 10021; Columbia University, College of Physicians and Surgeons, Center for Neurobiology and Behavior, New York, NY 10032; and Hunter College, New York, NY 10021
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1998-08-18
- Volume
- 95
- Issue
- 17
- Pages
- 9991-9996
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC21449
- OpenAlex
- W2105837661
- Cited by
- 864
- References
- 41
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 11 · 2023: 8 · 2022: 13 · 2021: 8 · 2020: 18 · 2019: 19 · 2018: 32 · 2017: 25 · 2016: 31 · 2015: 40 · 2014: 47 · 2013: 45 · 2012: 50
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- catechol-O-methyltransferase, catecholamine metabolism, dopamine, sexual dimorphism, anxiety-like behavior, aggression, sensorimotor gating, emotional reactivity, 22q11.2 deletion syndrome, striatum, frontal cortex, hypothalamus
- MeSH terms
- Amino Acid Sequence, Animals, Behavior, Animal, Mental Disorders, Brain, Catechol O-Methyltransferase, Catecholamines, Disease Models, Animal, Female, Heterozygote, Homozygote, Humans, Male, Mice, Inbred C57BL, Molecular Sequence Data, Phenotype, Sex Characteristics, Sequence Homology, Amino Acid, Mice, Knockout, Mice
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