Blockade of glucocorticoid receptors rapidly restores hippocampal CA1 synaptic plasticity after exposure to chronic stress.
Prolonged exposure to stressful events has been reported to inhibit the ability of hippocampal synapses to increase their synaptic efficacy. Here we tested if these effects could be prevented by blocking activation of glucocorticoid receptors during the last 4 days of the stress paradigm. In order to address this question, animals were exposed to 21 days of variable and inescapable stressors. Handled animals served as controls. During the last 4 days of the stress regime, animals were treated with the glucocorticoid receptor antagonist RU486. We found that 1 day after the last stressor, synaptic plasticity in the CA1 area of hippocampal slices is impaired in chronically stressed animals. Importantly, treating chronically stressed animals with RU486 for 4 days completely prevented this decrease in synaptic potentiation; RU486 treatment of handled controls did not affect potentiation. Treating hippocampal slices from control animals with high levels of corticosterone also impaired synaptic plasticity; this effect was similar for untreated and RU486-treated animals. Treating slices from chronically stressed animals with corticosterone did not further decrease synaptic plasticity. These data indicate that 4 days blockade of the glucocorticoid receptor, during a stress regime, is sufficient to fully restore synaptic plasticity.
Krugers
H J
HJ
SILS-CNS, University of Amsterdam, Kruislaan 320, 1098 SM, Amsterdam, the Netherlands. krugers@science.uva.nl
Goltstein
P M
PM
van der Linden
S
S
Joëls
M
M
D000818:Animals; D002908:Chronic Disease; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D006727:Hormone Antagonists / Q000008:administration & dosage; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000502:physiology*; D013315:Stress, Psychological / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone