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Null Mutation of 5α-Reductase Type I Gene Alters Ethanol Consumption Patterns in a Sex-Dependent Manner

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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.

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Acknowledgments

This research was supported by grants and resources from the Department of Veterans Affairs (DAF) and NIH grants RO1 AA012439 (DAF), P60 AA010760 (support for DAF), KO1 AA016849 (MMF), U01 AA013641 (support for MMF) and OD011092 (support for MMF). We would like to thank Ms. Sue Burkhart-Kasch for assistance with breeding and maintenance of the Srd5a1 mutant mouse colony, Dr. Xiaowei Zhang for genotyping the animals, and Ms. Andrea Murillo and Ms. Naomi Yoneyama for technical assistance. We also thank Drs. John Crabbe, Tamara Phillips, and Kristine Wiren for comments on an earlier version of this manuscript.

Conflict of Interest

Matthew Ford, Jeffrey Nickel, Moriah Kaufman, and Deborah Finn declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All institutional and national guidelines for the care and use of laboratory animals were followed.

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Authors and Affiliations

  1. Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR, 97239, USA

    Matthew M. Ford, Jeffrey D. Nickel, Moriah N. Kaufman & Deborah A. Finn

  2. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR, 97006, USA

    Matthew M. Ford

  3. Portland Alcohol Research Center, Veterans Affairs Medical Center, 3710 SW U.S. Veterans Hospital Road, Portland, OR, 97239, USA

    Deborah A. Finn

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  1. Matthew M. Ford
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Correspondence to Matthew M. Ford.

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Ford, M.M., Nickel, J.D., Kaufman, M.N. et al. Null Mutation of 5α-Reductase Type I Gene Alters Ethanol Consumption Patterns in a Sex-Dependent Manner. Behav Genet 45, 341–353 (2015). https://doi.org/10.1007/s10519-014-9694-2

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