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Corticosterone Increases Damage and Cytosolic Calcium Accumulation Associated With Ethanol Withdrawal in Rat Hippocampal Slice Cultures
Author(s) -
Mulholland Patrick J.,
Self Rachel L.,
Harris Barton R.,
Little Hilary J.,
Littleton John M.,
Prendergast Mark A.
Publication year - 2005
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000163509.27577.da
Subject(s) - corticosterone , hippocampal formation , cytosol , ethanol , calcium , chemistry , endocrinology , medicine , microbiology and biotechnology , biology , biochemistry , hormone , enzyme
Background: Evidence suggests that stress hormones (i.e., glucocorticoids) may be increased during acute or chronic consumption of ethanol and during withdrawal from ethanol consumption, effects that may contribute to the development of cognitive impairment. The goal of the current studies was to examine the hypothesis that increased glucocorticoid levels in conjunction with ethanol exposure and withdrawal may cause hippocampal damage. Methods: Organotypic hippocampal slice cultures were exposed to 50 mM ethanol for 10 days and withdrawn for 1 day. After withdrawal, cytotoxicity and cytosolic Ca 2+ accumulation were measured using the nucleic acid stain propidium iodide and Calcium Orange, AM, respectively. Cultures were also treated with nontoxic concentrations of corticosterone (0.001–1 μM) during ethanol exposure and withdrawal or only during withdrawal. Additional cultures were coexposed to corticosterone and RU486 (0.1–10.0 μM), spironolactone (0.1–10.0 μM), or MK‐801 (20 μM) during ethanol exposure and/or withdrawal. Results: Ethanol withdrawal did not increase propidium iodide fluorescence and cytosolic Ca 2+ levels. However, significant increases in propidium iodide fluorescence and in cytosolic Ca 2+ accumulation were observed in cultures when corticosterone (≥ 100 nM) was exposed during ethanol treatment and/or withdrawal. These effects of corticosterone on ethanol withdrawal were attenuated by RU486 and MK‐801 but not by spironolactone coexposure. Conclusions: This report demonstrated that corticosterone exposure during ethanol treatment and/or withdrawal resulted in significant hippocampal damage, possibly via activation of glucocorticoid receptors and enhancement of the glutamatergic cascade. The findings from these studies suggest that glucocorticoids contribute to the neuropathological consequences of alcohol dependence in humans.