title: Null mutation of 5α-reductase type I gene alters ethanol consumption patterns in a sex-dependent manner.
abstract: The neuroactive steroid allopregnanolone (ALLO) is a positive modulator of GABAA receptors, and manipulation of neuroactive steroid levels via injection of ALLO or the 5α-reductase inhibitor finasteride alters ethanol self-administration patterns in male, but not female, mice. The Srd5a1 gene encodes the enzyme 5α-reductase-1, which is required for the synthesis of ALLO. The current studies investigated the influence of Srd5a1 deletion on voluntary ethanol consumption in male and female wildtype (WT) and knockout (KO) mice. Under a continuous access condition, 6 and 10 % ethanol intake was significantly greater in KO versus WT females, but significantly lower in KO versus WT males. In 2-h limited access sessions, Srd5a1 deletion retarded acquisition of 10 % ethanol intake in female mice, but facilitated it in males, versus respective WT mice. The present findings demonstrate that the Srd5a1 gene modulates ethanol consumption in a sex-dependent manner that is also contingent upon ethanol access condition and concentration.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR, 97239, USA, fordma@ohsu.edu.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Ford
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Nickel
authors.forename: Moriah N
authors.initials: MN
authors.lastname: Kaufman
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Finn
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000235:genetics*; D000483:Alleles; D000818:Animals; D001706:Biopsy; D000431:Ethanol / Q000097:blood*; D005260:Female; D018120:Finasteride / Q000737:chemistry; D005838:Genotype; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D011280:Pregnanolone; D011963:Receptors, GABA-A / Q000378:metabolism; D011995:Recombination, Genetic; D012439:Saccharin / Q000737:chemistry; D012737:Sex Factors; D013256:Steroids
chemical_list: D008565:Membrane Proteins; D011963:Receptors, GABA-A; D013256:Steroids; D000431:Ethanol; D018120:Finasteride; D011280:Pregnanolone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C518406:Srd5a1 protein, mouse; D012439:Saccharin