Localization of brain 5α-reductase messenger RNA in mice selectively bred for high chronic alcohol withdrawal severity

Charles Roselli, Timothy J. Finn, Sean M. Ronnekleiv-Kelly, Michelle A. Tanchuck, Katherine R. Kaufman, Deborah (Deb) Finn

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Several lines of evidence suggest that fluctuations in endogenous levels of the γ-aminobutyric acid (GABA)ergic neurosteroid allopregnanolone (ALLO) represent one mechanism for regulation of GABAergic inhibitory tone in the brain, with an ultimate impact on behavior. Consistent with this idea, there was an inverse relationship between ALLO levels and symptoms of anxiety and depression in humans and convulsive activity in rodents during alcohol withdrawal. Our recent studies examined the activity and expression of 5α-reductase (Srd5a1), the rate-limiting enzyme in the biosynthesis of ALLO, during alcohol withdrawal in mice selectively bred for high chronic alcohol withdrawal (Withdrawal Seizure-Prone [WSP]) and found that Srd5a1 was downregulated in the cortex and hippocampus over the time course of dependence and withdrawal. The purpose of the present studies was to extend these findings and more discretely map the regions of Srd5a1 expression in mouse brain using radioactive in situ hybridization in WSP mice that were ethanol naïve, following exposure to 72. h ethanol vapor (dependent) or during peak withdrawal. In naïve animals, expression of Srd5a1 was widely distributed throughout the mouse brain, with highest expression in specific regions of the cerebral cortex, hippocampus, thalamus, hypothalamus, and amygdala. In dependent animals and during withdrawal, there was no change in Srd5a1 expression in cortex or hippocampus, which differed from our recent findings in dissected tissues. These results suggest that local Srd5a1 mRNA expression in WSP brain may not change in parallel with local ALLO content or withdrawal severity.

Original languageEnglish (US)
Pages (from-to)763-772
Number of pages10
JournalAlcohol
Volume45
Issue number8
DOIs
StatePublished - Dec 2011

Fingerprint

Pregnanolone
withdrawal
Brain
Oxidoreductases
brain
alcohol
Alcohols
Hippocampus
Messenger RNA
Seizures
Animals
Ethanol
seizure
Aminobutyrates
Biosynthesis
Amygdala
Thalamus
Human Activities
Cerebral Cortex
gamma-Aminobutyric Acid

Keywords

  • Convulsion
  • Ethanol
  • GABA
  • In situ hybridization
  • Neurosteroid

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Behavioral Neuroscience
  • Neurology
  • Toxicology
  • Health(social science)

Cite this

Localization of brain 5α-reductase messenger RNA in mice selectively bred for high chronic alcohol withdrawal severity. / Roselli, Charles; Finn, Timothy J.; Ronnekleiv-Kelly, Sean M.; Tanchuck, Michelle A.; Kaufman, Katherine R.; Finn, Deborah (Deb).

In: Alcohol, Vol. 45, No. 8, 12.2011, p. 763-772.

Research output: Contribution to journalArticle

Roselli, Charles ; Finn, Timothy J. ; Ronnekleiv-Kelly, Sean M. ; Tanchuck, Michelle A. ; Kaufman, Katherine R. ; Finn, Deborah (Deb). / Localization of brain 5α-reductase messenger RNA in mice selectively bred for high chronic alcohol withdrawal severity. In: Alcohol. 2011 ; Vol. 45, No. 8. pp. 763-772.
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