Sex Differences in Ethanol’s Anxiolytic Effect and Chronic Ethanol Withdrawal Severity in Mice with a Null Mutation of the 5α-Reductase Type 1 Gene

Michelle A. Tanchuck-Nipper, Matthew M. Ford, Anna Hertzberg, Amy Beadles-Bohling, Debra K. Cozzoli, Deborah A. Finn

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Manipulation of endogenous levels of the GABAergic neurosteroid allopregnanolone alters sensitivity to some effects of ethanol. Chronic ethanol withdrawal decreases activity and expression of 5α-reductase-1, an important enzyme in allopregnanolone biosynthesis encoded by the 5α-reductase-1 gene (Srd5a1). The present studies examined the impact of Srd5a1 deletion in male and female mice on several acute effects of ethanol and on chronic ethanol withdrawal severity. Genotype and sex did not differentially alter ethanol-induced hypothermia, ataxia, hypnosis, or metabolism, but ethanol withdrawal was significantly lower in female versus male mice. On the elevated plus maze, deletion of the Srd5a1 gene significantly decreased ethanol’s effect on total entries versus wildtype (WT) mice and significantly decreased ethanol’s anxiolytic effect in female knockout (KO) versus WT mice. The limited sex differences in the ability of Srd5a1 genotype to modulate select ethanol effects may reflect an interaction between developmental compensations to deletion of the Srd5a1 gene with sex hormones and levels of endogenous neurosteroids.

Original languageEnglish (US)
Pages (from-to)354-367
Number of pages14
JournalBehavior genetics
Volume45
Issue number3
DOIs
StatePublished - May 1 2015

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Keywords

  • Alcohol
  • Allopregnanolone
  • GABA
  • Hypnosis
  • Metabolism
  • Neurosteroid

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Genetics(clinical)

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