liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Binge-like ethanol consumption increases corticosterone levels and neurodegneration whereas occupancy of type II glucocorticoid receptors with mifepristone is neuroprotective
National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
National Institute of Mental Health, NIH, Bethesda, MD, USA.
National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
Show others and affiliations
2014 (English)In: Addiction Biology, ISSN 1355-6215, E-ISSN 1369-1600, Vol. 19, no 1, p. 27-36Article in journal (Refereed) Published
Abstract [en]

Excessive ethanol (EtOH) use leads to impaired memory and cognition. Using a rat model of binge-like intoxication, we tested whether elevated corticosterone (Cort) levels contribute to the neurotoxic consequences of EtOH exposure. Rats were adrenalectomized (Adx) and implanted with cholesterol pellets, or cholesterol pellets containing Cort in order to achieve basal, medium, or high blood concentrations of Cort. Intragastric EtOH or an isocaloric control solution was given three times daily for 4 days to achieve blood alcohol levels ranging between 200 and 350 mg/dl. Mean 24-hour plasma levels of Cort were ∼110 and ∼40 ng/ml in intact EtOH-treated and intact control animals, respectively. Basal Cort replacement concentrations in EtOH-treated Adx animals did not exacerbate alcohol-induced neurodegeneration in the hippocampal dentate gyrus (DG) or the entorhinal cortex (EC) as observed by amino-cupric silver staining. In contrast, Cort replacement pellets resulting in plasma Cort levels twofold higher (medium) than normal, or greater than twofold higher (high) in Adx-Cort-EtOH animals increased neurodegeneration. In separate experiments, pharmacological blockade of the Type II glucocorticoid (GC) receptor was initiated with mifepristone (RU38486; 0, 5, 15 mg/kg/day, i.p.). At the higher dose, mifepristone decreased the number of degenerating hippocampal DG cells in binge-EtOH-treated intact animals, whereas, only a trend for reduction was observed in 15 mg/kg/day mifepristone-treated animals in the EC, as determined by fluoro-jade B staining. These results suggest that elevated circulating Cort in part mediates EtOH-induced neurotoxicity in the brain through activation of Type II GC receptors.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014. Vol. 19, no 1, p. 27-36
Keywords [en]
corticosterone, ethanol, FJ-B, hippocampus, mifepristone, neurodegeneration
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-101831DOI: 10.1111/j.1369-1600.2012.00451.xISI: 000328610300004PubMedID: 22500955OAI: oai:DiVA.org:liu-101831DiVA, id: diva2:666739
Available from: 2013-11-24 Created: 2013-11-24 Last updated: 2018-01-11

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records

Thorsell, AnnikaHeilig, Markus

Search in DiVA

By author/editor
Thorsell, AnnikaHeilig, Markus
In the same journal
Addiction Biology
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 181 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf