title: Brief RU 38486 treatment normalizes the effects of chronic stress on calcium currents in rat hippocampal CA1 neurons.
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 CA1 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 naïve 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 CA1 neurons. This could have consequences for the viability of these neurons.
authors.affiliation: SILS-CNS, University of Amsterdam, Amsterdam, The Netherlands. karst@science.uva.nl
authors.forename: Henk
authors.initials: H
authors.lastname: Karst
authors.forename: Marian
authors.initials: M
authors.lastname: Joëls
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation; D006624:Hippocampus / Q000473:pathology*; D006727:Hormone Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D015735:Mifepristone / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000473:pathology*
chemical_list: D006727:Hormone Antagonists; D015735:Mifepristone; D002118:Calcium; D003345:Corticosterone