Plasticity of the GABA(A) receptor subunit cassette in response to stressors in reactive versus resilient mice.
GABA(A) functioning has been implicated in anxiety and depressive disorders. In this regard, we suggested that in addition to analyzing GABA(A) and the subunits that comprise the GABA(A) receptor, it might be profitable to assess the coordinated expression of subunits that comprise the GABA(A) 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 GABA(A) 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 GABA(A) functioning in stressor-related psychological disturbances.
Poulter
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Molecular Brain (Research Group), Robarts Research Institute, Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada. mpoulter@robarts.ca
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Zhurov
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Merali
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Anisman
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D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology*; D002908:Chronic Disease; D003863:Depression / Q000503:physiopathology; D019422:Dietary Sucrose; D005247:Feeding Behavior / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D011963:Receptors, GABA-A / Q000378:metabolism*; D013045:Species Specificity; D013315:Stress, Psychological / Q000503:physiopathology*
D019422:Dietary Sucrose; D012333:RNA, Messenger; D011963:Receptors, GABA-A