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001-es BibID:BIBFORM102832
035-os BibID:(WOS)000632036200007 (Scopus)85101314728
Első szerző:Huzian Orsolya
Cím:Stress Resilience is Associated with Hippocampal Synaptoprotection in the Female Rat Learned Helplessness Paradigm / Huzian Orsolya, Baka Judith, Csakvari Eszter, Dobos Nikoletta, Leranth Csaba, Siklos Laszlo, Duman Ronald S., Farkas Tamas, Hajszan Tibor
Dátum:2021
ISSN:0306-4522
Megjegyzések:The synaptogenic hypothesis of major depressive disorder implies that preventing the onset of depressive-like behavior also prevents the loss of hippocampal spine synapses. By applying the psychoactive drugs, diazepam and fluoxetine, we investigated whether blocking the development of helpless behavior by promoting stress resilience in the rat learned helplessness paradigm is associated with a synaptoprotective action in the hippocampus. Adult ovariectomized and intact female Sprague-Dawley rats (n= 297) were treated with either diazepam, fluoxetine, or vehicle, exposed to inescapable footshocks or sham stress, and tested in an active escape task to assess helpless behavior. Escape-evoked corticosterone secretion, as well as remodeling of hippocampal spine synapses at a timepoint representing the onset of escape testing were also analyzed. In ovariectomized females, treatment with diazepam prior to stress exposure prevented helpless behavior, blocked the loss of hippocampal spine synapses, and muted the corticosterone surge evoked by escape testing. Although fluoxetine stimulated escape performance and hippocampal synaptogenesis under non-stressed conditions, almost all responses to fluoxetine were abolished following exposure to inescapable stress. Only a much higher dose of fluoxetine was capable of partly reproducing the strong protective actions of diazepam. Importantly, these protective actions were retained in the presence of ovarian hormones. Our findings indicate that stress resilience is associated with the preservation of spine synapses in the hippocampus, raising the possibility that, besides synaptogenesis, hippocampal synaptoprotection is also implicated in antidepressant therapy. 2021 The Author (s). Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY license
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
diazepam
fluoxetine
major depression
corticosterone
synaptic plasticity
antidepressant resistance
Megjelenés:Neuroscience. - 459 (2021), p. 85-103. -
További szerzők:Baka Judith Csakvari Eszter Dobos Nikoletta (1981-) (biológus) Leranth Csaba Siklós László Duman Ronald S. Farkas Tamás (1971-) (biológus) Hajszan Tibor
Pályázati támogatás:TÁMOP-4.2.4.A/2-11-1-2012-0001
TÁMOP
GINOP-2.3.2-15-2016-00001
GINOP
GINOP-2.3.2-15-2016-00034
GINOP
81190
OTKA
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