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The Journal of Neuroscience, July 1, 2001, 21(13):4822-4829
Psychological Stress Increases Hippocampal Mineralocorticoid
Receptor Levels: Involvement of Corticotropin-Releasing Hormone
Angela
Gesing,
Alicia
Bilang-Bleuel,
Susanne K.
Droste,
Astrid C. E.
Linthorst,
Florian
Holsboer, and
Johannes M. H. M.
Reul
Max Planck Institute of Psychiatry, Section of
Neuropsychopharmacology, 80804 Munich, Germany
We investigated whether acute stressors regulate functional
properties of the hippocampal mineralocorticoid receptor (MR), which
acts inhibitory on hypothalamic-pituitary-adrenocortical activity.
Exposure of rats to forced swimming or novelty evoked a significant
rise in density of MR immunoreactivity in all hippocampal subfields
after 24 hr, whereas exposure to a cold environment was ineffective.
Time course analysis revealed that the effect of forced swimming on MR
peaked at 24 hr and returned to control levels between 24 and 48 hr. In
pyramidal neurons of CA2 and CA3, marked rises were already observed
after 8 hr. Radioligand binding assays showed that
corticotropin-releasing hormone (CRH) injected intracerebroventricularly into adrenalectomized rats also
produced a rise in hippocampal MR levels; an effect for which the
presence of corticosterone, but not dexamethasone, at the time of
injection was a prerequisite. Moreover, pretreatment with the CRH
receptor antagonist
(D-Phe12,Nle21,38, -Me-Leu37)-CRH12-41
blocked the effect of forced swimming on hippocampal MR levels. To
investigate whether the rise in MR levels had any functional
consequences for HPA regulation, 24 hr after forced swimming, a
challenge test with the MR antagonist RU 28318 was conducted. The
forced swimming exposed rats showed an enhanced MR-mediated inhibition
of HPA activity.
This study identifies CRH as an important regulator of MR, a pathway
with marked consequence for HPA axis regulation. We conclude that the
interaction between CRH and MR presents a novel mechanism involved in
the adaptation of the brain to psychologically stressful events.
Key words:
mineralocorticoid receptor; HPA axis; corticotropin-releasing hormone; ACTH; glucocorticoid hormone; hippocampus; stress
Copyright © 2001 Society for Neuroscience 0270-6474/01/21134822-08$05.00/0
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