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

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

doi:10.1016/j.bbr.2011.12.014

Cited by 38Neurotransmitter Receptor Influence on BehaviorStress Responses and CortisolPharmacogenetics and Drug Metabolism

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

Desbonnet, Lieve, Tighe, Orna, Karayiorgou, Maria, Gogos, Joseph A., Waddington, John L., O’Tuathaigh, Colm M.P.·2012·Behavioural Brain Research

DOI 10.1016/j.bbr.2011.12.014

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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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The COMT gene is crucially involved in the stress response.
“and the COMT gene seems to be crucially involved in the stress response [25].”
From Dynamic DNA methylation changes in the COMT gene promoter region in response to mental stress and its modulation by transcranial direct current stimulation (2021) · cites this paper as [25]

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Authors: Desbonnet, L., Tighe, O., Karayiorgou, M., Gogos, J. A., Waddington, J. L., & O’Tuathaigh, C. M. P.
Affiliations: Royal College of Surgeons in Ireland (IE)
Columbia University (US)
University College Cork (IE)
Corresponding author: O’Tuathaigh, Colm M.P.
ORCID: Desbonnet, Lieve
Tighe, Orna
Karayiorgou, Maria
Gogos, Joseph A.
Waddington, John L.
O’Tuathaigh, Colm M.P.
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2012-03
Volume: 228
Issue: 2
Pages: 351-358
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/j.bbr.2011.12.014
OpenAlex: W2147422917
Cited by: 38
References: 79
Citations by year: 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 6 · 2014: 7 · 2013: 3 · 2012: 3
FWCI: 1.72
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Behavioural Brain Research (publishedVersion)
PubMed (publishedVersion)
ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
Funders: Health Research Board (PD/2007/20)
Science Foundation Ireland (07/IN.1/B960)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords: catechol-O-methyltransferase, anxiety, stress responsivity, acute restraint stress, chronic restraint stress, corticosterone, cytokines, benzodiazepine sensitivity, midazolam, chlordiazepoxide, tolcapone, COMT inhibition, light/dark test, female mice, catecholamines
MeSH terms: Tolcapone, Analysis of Variance, Animals, Behavior, Animal, Benzophenones, Catechol O-Methyltransferase, Chlordiazepoxide, Corticosterone, Dark Adaptation, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme Inhibitors, Female, Male, Mice, Inbred C57BL, Midazolam, Nitrophenols, Organ Size, Restraint, Physical, Statistics as Topic, Stress, Psychological, Time Factors, Anti-Anxiety Agents, Cytokines, Mice, Knockout, Mice

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

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