Plasticity of the GABAA receptor subunit cassette in response to stressors in reactive versus resilient mice

• Published in: Neuroscience 2010-02, Vol.165 (4), p.1039-1051
• Main Authors: Poulter, M.O, Du, L, Zhurov, V, Merali, Z, Anisman, H
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Biological and medical sciences; depression; Fundamental and applied biological sciences. Psychology; GABAA receptors; human; Medical sciences; mouse; Neurology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; stress; Suicide; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.11.028

Abstract GABAA functioning has been implicated in anxiety and depressive disorders. In this regard, we suggested that in addition to analyzing GABAA and the subunits that comprise the GABAA receptor, it might be profitable to assess the coordinated expression of subunits that comprise the GABAA receptor cassette. We demonstrate that certain subunits within stress-sensitive brain regions were higher in stressor reactive BALB/cByJ than in hardy C57BL/6ByJ mice, and that a chronic, intermittent, variable stressor (6 days/week over 7 weeks) differentially influenced subunit expression in these strains. Further, mRNA expression of GABAA subunits were highly coordinated (inter-correlated), and markedly altered by stressors, once again varying with brain region. At the central amygdala of BALB/cByJ mice the ordinarily high subunit inter-relations were reduced in acutely stressed mice, and this outcome was exacerbated with a chronic stressor. In C57BL/6ByJ mice subunit inter-relations were lower than in BALB/cByJ mice; the acute stressor increased subunit organization, which returned to control levels with following a chronic stressor. The profile of amygdala subunit inter-relations was recapitulated in a step-down behavioral test; anxiety was increased by acute and chronic stressors in BALB/cByJ mice, but in the C57BL/6ByJ strain the elevated anxiety associated with an acute stressor was not apparent after chronic stressor treatment. The anxiety could be dissociated from apparent anhedonia (reflected by free sucrose consumption) where the preference for sucrose was reduced by an acute stressor, but this outcome was more pronounced following a chronic stressor, especially in BALB/cByJ mice. These findings support the view that analyses involving subunit organization, rather than just differences in absolute levels, may be expedient in assessing GABAA functioning in stressor-related psychological disturbances.