Systemic ethanol administration elevates deoxycorticosterone levels and chronic ethanol exposure attenuates this response

Systemic ethanol administration is known to elevate levels of the GABAergic neuroactive steroid 3α,21-dihydroxy-5α-pregnan-20-one (3α,5α-THDOC). 3α,5α-THDOC is synthesized from deoxycorticosterone (DOC) by metabolism in adrenals and brain. The present study investigated DOC levels in plasma and brai...

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Bibliographic Details
Published in:Brain research 2005-07, Vol.1049 (1), p.104-111
Main Authors: Khisti, Rahul T., Boyd, Kevin N., Kumar, Sandeep, Morrow, A. Leslie
Format: Article
Language:English
Subjects:
3α,5α-THDOC
Alcoholism - metabolism
Alcoholism and acute alcohol poisoning
Analysis of Variance
Animals
Biological and medical sciences
Brain - drug effects
Brain - metabolism
Chronic ethanol consumption
Deoxycorticosterone
Desoxycorticosterone - analogs & derivatives
Desoxycorticosterone - blood
Desoxycorticosterone - metabolism
Drug Administration Schedule
Ethanol
Ethanol - administration & dosage
Injections
Male
Medical sciences
Neuroactive steroid
Rats
Rats, Sprague-Dawley
Statistics, Nonparametric
Toxicology
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Summary:Systemic ethanol administration is known to elevate levels of the GABAergic neuroactive steroid 3α,21-dihydroxy-5α-pregnan-20-one (3α,5α-THDOC). 3α,5α-THDOC is synthesized from deoxycorticosterone (DOC) by metabolism in adrenals and brain. The present study investigated DOC levels in plasma and brain following ethanol administration to naïve and ethanol-exposed rats. Rats were administered ethanol (2 g/kg, i.p.) or saline and DOC levels were measured in plasma and brain regions by radioimmunoassay. Chronic ethanol-exposed rats were administered an ethanol challenge (2 g/kg, i.p.) following 15 days of ethanol liquid diet consumption. Ethanol administration markedly increased DOC levels in plasma, cerebral cortex, hippocampus, hypothalamus, cerebellum, and olfactory tubercle of naïve rats. Ethanol challenge produced an attenuated elevation of DOC in rat plasma and brain following chronic ethanol consumption for 2 weeks. These findings suggest that acute ethanol increases DOC levels in ethanol naïve rats and chronic ethanol consumption induces tolerance to ethanol-induced increases in DOC levels.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2005.05.007