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Hippocampal GABAergic dysfunction in a rat chronic mild stress model of depression
Author(s) -
Holm Mai Marie,
NietoGonzalez Jose Luis,
Vardya Irina,
Henningsen Kim,
Jayatissa Magdaleiepsuj,
Wiborg Ove,
Jensen Kimmo
Publication year - 2011
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20758
Subject(s) - dentate gyrus , gabaergic , neuroscience , hippocampal formation , parvalbumin , inhibitory postsynaptic potential , tonic (physiology) , psychology , interneuron , granule cell , gabaa receptor , chronic stress , medicine , receptor
In major depression, one line of research indicates that a dysfunctional GABAergic inhibitory system is linked to the appearance of depressive symptoms. However, as the mechanistic details of such GABAergic deficit are largely unknown, we undertook a functional investigation of the GABAergic system in the rat chronic mild stress model of depression. Adult rats were exposed to an eight‐week long stress protocol leading to anhedonic‐like behavior. In hippocampal brain slices, phasic, and tonic GABA A receptor‐mediated currents in dentate gyrus granule cells were examined using patch‐clamp recordings. In granule cells, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was reduced to 41% in anhedonic‐like rats, which was associated with a reduced probability of evoked GABA release. Using immunohistochemical analysis, there was no change in the number of parvalbumin‐positive interneurons in the dentate gyrus. Notably, we observed a 60% increase in THIP‐activated tonic GABA A mediated current in anhedonic‐like rats, suggesting an upregulation of extrasynaptic GABA A receptors. Finally, five weeks treatment with the antidepressant escitalopram partially reversed the sIPSCs frequency. In summary, we have revealed a hippocampal dysfunction in the GABAergic system in the chronic mild stress model of depression in rats, caused by a reduction in action potential‐dependent GABA release. Since the function of the GABAergic system was improved by antidepressant treatment, in parallel with behavioral read outs, it suggests a role of the GABAergic system in the pathophysiology of depression. © 2010 Wiley‐Liss, Inc.