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

Issue Title: Special Issue: Gene-Hormone Interplay Manipulation of endogenous levels of the GABAergic neurosteroid allopregnanolone alters sensitivity to some effects of ethanol. Chronic ethanol withdrawal decreases activity and expression of 5[alpha]-reductase-1, an important enzyme in allopregnano...

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Bibliographic Details
Published in:Behavior genetics 2015-05, Vol.45 (3), p.354
Main Authors: Tanchuck-nipper, Michelle A, d, Matthew M, Hertzberg, Anna, Beadles-bohling, Amy, Cozzoli, Debra K, Finn, Deborah A
Format: Article
Language:English
Subjects:
Biosynthesis
Chromosomes
Enzymes
Ethanol
Gender differences
Genes
Genomics
Metabolism
Mutation
Neurosciences
Steroids
Veterans
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Summary:Issue Title: Special Issue: Gene-Hormone Interplay Manipulation of endogenous levels of the GABAergic neurosteroid allopregnanolone alters sensitivity to some effects of ethanol. Chronic ethanol withdrawal decreases activity and expression of 5[alpha]-reductase-1, an important enzyme in allopregnanolone biosynthesis encoded by the 5[alpha]-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.
ISSN:0001-8244
1573-3297
DOI:10.1007/s10519-014-9691-5