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Physiological and behavioural responsivity to stress and anxiogenic stimuli in COMT-deficient mice

Overview of attention for article published in Behavioural Brain Research, December 2011
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Title
Physiological and behavioural responsivity to stress and anxiogenic stimuli in COMT-deficient mice
Published in
Behavioural Brain Research, December 2011
DOI 10.1016/j.bbr.2011.12.014
Pubmed ID
Authors

Lieve Desbonnet, Orna Tighe, Maria Karayiorgou, Joseph A. Gogos, John L. Waddington, Colm M.P. O’Tuathaigh

Abstract

Catechol-O-methyltransferase, an enzyme involved in regulating brain catecholamine levels, has been implicated in anxiety, pain and/or stress responsivity. Elements of this putative association remain unclarified, notably whether: (a) COMT variation modulates responses to acute and/or chronic stress equally; (b) acute pharmacological inhibition of COMT produces comparable effects on anxiety to that observed after deletion of the COMT gene; (c) COMT genotype modulates action of anxiolytic drugs. We aimed to further investigate the relationship between reduced COMT function, anxiety and stress responsivity in mice. To compare the effect of acute vs. chronic restraint stress in female COMT KO vs. WT mice, serum corticosterone and cytokine concentrations were measured [Experiment 1]. Sensitivity to the benzodiazepines midazolam and chlordiazepoxide in the light-dark test was assessed in female COMT KO vs. WT mice [Experiment 2]. Effects of acute administration of the COMT inhibitor tolcapone, and of these same benzodiazepines thereon, in the light-dark test were assessed in female C57BL/6 mice [Experiment 3]. COMT KO mice demonstrated an increased corticosterone response to acute but not chronic stress, and a modified cytokine profile after chronic, but not acute stress. COMT KO mice showed increased anxiety, but benzodiazepine sensitivity was affected by COMT genotype. Whilst tolcapone had no effect on light/dark performance in C57BL6/J mice it decreased benzodiazepine sensitivity. These data elaborate earlier findings of increased anxiety in female COMT KO mice and also clarify a role for COMT in modulating stress-related hormonal and immune parameters in a manner that depends on chronicity of the stressor.

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Mendeley readers

The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 3%
Denmark 1 3%
Unknown 34 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 19%
Researcher 6 17%
Student > Master 5 14%
Student > Doctoral Student 4 11%
Other 3 8%
Other 7 19%
Unknown 4 11%
Readers by discipline Count As %
Medicine and Dentistry 6 17%
Psychology 6 17%
Agricultural and Biological Sciences 6 17%
Neuroscience 4 11%
Biochemistry, Genetics and Molecular Biology 1 3%
Other 5 14%
Unknown 8 22%