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

Desbonnet, L., Tighe, O., Karayiorgou, M., Gogos, J. A., Waddington, J. L. and O’Tuathaigh, C. M.P. (2012) Physiological and behavioural responsivity to stress and anxiogenic stimuli in COMT-deficient mice. Behavioural Brain Research, 228(2), pp. 351-358. (doi: 10.1016/j.bbr.2011.12.014)

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.<p></p> We aimed to further investigate the relationship between reduced COMT function, anxiety and stress responsivity in mice.<p></p> 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].<p></p> 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.<p></p> 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Desbonnet, Dr Lieve
• Authors: Desbonnet, L., Tighe, O., Karayiorgou, M., Gogos, J. A., Waddington, J. L., and O’Tuathaigh, C. M.P.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: Behavioural Brain Research
• Publisher: Elsevier B.V.
• ISSN: 0166-4328
• ISSN (Online): 1872-7549