Brief RU 38486 treatment normalizes the effects of chronic stress on calcium currents in rat hippocampal CAI neurons

Henk Karst*, Marian Joels

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Scopus)

Abstract

Chronic stress alters many properties in rat brain, like serotonin responsiveness and dendritic morphology. In the present study, we examined (i) whether unpredictable stress during 21 days affects calcium (Ca) currents of CAI pyramidal neurons recorded on day 22; and (ii) if so, whether this change is normalized by treatment with the glucocorticoid receptor-antagonist RU 38486 during days 18 - 21. At 3 weeks of unpredictable stress increased the amplitude of the peak and sustained calcium current components, determined in hippocampal slices prepared from animals under rest (ie, with low corticosterone levels). The increased Ca-current amplitude was associated with an enhanced cell capacitance; current density was not significantly affected by chronic stress. In slices from stressed rats that received RU 38486, no stress-induced enhancement of calcium current amplitude was seen, while RU 38486 by itself did not alter calcium currents in handled controls. We confirmed earlier observations that brief in vitro treatment with 100 nM corticosterone, thus substantially activating the low-affinity glucocorticoid receptors, increases Ca-current amplitude recorded 1 - 4 h later in slices from naive rats. However, Ca-current amplitude was not affected by corticosterone applied to slices from handled controls and currents were even decreased by corticosterone given to slices from chronically stressed rats, suggesting that corticosterone effects depend on the history of the animal. In conclusion, the data indicate that chronic stress, RU 38486 treatment as well as acute rises in corticosterone level strongly modulate calcium influx into CAI neurons. This could have consequences for the viability of these neurons.

Original languageEnglish
Pages (from-to)1830-1839
Number of pages10
JournalNeuropsychopharmacology
Volume32
Issue number8
DOIs
Publication statusPublished - Aug-2007
Externally publishedYes

Keywords

  • unpredictable stress
  • glucocorticoid receptor
  • capacitance
  • current amplitude
  • whole cell recording
  • COMBINED DEXAMETHASONE/CRH TEST
  • PITUITARY-ADRENOCORTICAL AXIS
  • MEDIAL PREFRONTAL CORTEX
  • PYRAMIDAL NEURONS
  • PSYCHOTIC DEPRESSION
  • APICAL DENDRITES
  • GENE-EXPRESSION
  • INDUCED ATROPHY
  • ANTIDEPRESSANT TIANEPTINE
  • CORTICOSTEROID ACTIONS

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