Catechol- O -methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior

Proceedings of the National Academy of Sciences of the United States of America - Tập 95 Số 17 - Trang 9991-9996 - 1998
Joseph A. Gogos1, Maria A. Morgan1, Victoria N. Luine1, Miklós Sántha1, Sonoko Ogawa1, Donald W. Pfaff1, Maria Karayiorgou1
1The 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

Tóm tắt

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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Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 95 Số 17

9991-9996

Thông tin tác giả