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Ethanol Withdrawal-Associated Drinking and Drinking in the Dark: Common and Discrete Genetic Contributions

1 / Pamela Metten1 / Lawrence C. Huang1 / Jason P. Schlumbohm1 / Stephanie E. Spence1 / Amanda M. Barkley-Levenson1 / Deborah A. Finn1 / Justin S. Rhodes2 / Andy J. Cameron1

1Portland Alcohol Research Center, VA Medical Center, and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA

2Neuroscience Program, The Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA

©2012 by Versita. This content is open access.

Citation Information: Addiction Genetics. Volume 1, Pages 3–11, ISSN (Online) 2084-7688, DOI: https://doi.org/10.2478/addge-2012-0002, October 2012

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Ethanol Withdrawal-Associated Drinking and Drinking in the Dark: Common and Discrete Genetic Contributions

Individual mice differ in the dose of ethanol they will ingest voluntarily when it is offered during limited access periods in the circadian dark, a phenotype called drinking in the dark (DID). Substantial genetic variation in DID has been reported across a few standard inbred mouse strains, and a line of High Drinking in the Dark (HDID) mice has been established through selective breeding on the blood ethanol concentration (BEC) they attain at the end of a drinking session. Here, we report ethanol DID data for 23 inbred mouse strains, including 11 not previously reported, corroborating the genetic contributions to this trait. We also report data on a different ethanol drinking trait, the increased intake seen after multiple cycles of chronic intermittent exposure to ethanol vapor (CIE). Drinking escalated significantly during ethanol withdrawal. However, HDID mice and their HS controls showed equivalent escalation during withdrawal, demonstrating that withdrawal-associated drinking escalation is not a clear genetic correlate of selection on DID. Across inbred strains, DID is substantially genetically correlated with previously-published twobottle ethanol preference drinking data assessed under conditions of continuous ethanol access. Although inbred strain data for withdrawalassociated drinking are not available, the current pattern of results suggests that withdrawal-associated drinking is genetically distinct from DID, while genetic contributions to DID and two-bottle preference drinking are substantially similar.

Keywords: Withdrawal; Drinking; Preference; Genetics; Mouse; Selective breeding; Inbred strains; Chronic intermittent exposure; Dependence

  • Mardones J, Segovia-Riquelme N (1983) Thirty-two years of selection of rats by ethanol preference: UChA and UChB strains. Neurobehav Toxicol Teratol 5:171-8. [PubMed]

  • McClearn GE, Rodgers DA (1959) Differences in alcohol preference among inbred strains of mice. Quart J Stud Alcohol 20:691-5.

  • Crabbe JC, Phillips TJ, Belknap JK (2010) The complexity of alcohol drinking: studies in rodent genetic models. Behav Genet 40:737-50. [PubMed] [Crossref] [Web of Science]

  • Wahlsten D, Bachmanov A, Finn DA, Crabbe JC (2006) Stability of inbred mouse strain differences in behavior and brain size between laboratories and across decades. Proc Natl Acad Sci USA 103:16364-9. [Crossref]

  • NIAAA Council Approves Definition of Binge Drinking. NIAAA Newsletter 2004;3.

  • Rhodes JS, Best K, Belknap JK, Finn DA, Crabbe JC (2005) Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice. Physiol Behav 84:53-63. [Crossref]

  • Rhodes JS, Ford MM, Yu C-H, Brown LL, Finn DA, Garland Jr. T, et al (2007) Mouse inbred strain differences in ethanol drinking to intoxication. Genes Brain Behav 6:1-18. [Web of Science] [Crossref] [PubMed]

  • Crabbe JC, Metten P, Rhodes JS, Yu C-H, Brown LL, Phillips TJ, et al (2009) A line of mice selected for high blood ethanol concentrations shows drinking in the dark to intoxication. Biol Psychiat 65:662-70. [Web of Science] [Crossref]

  • Becker HC, Lopez MF (2004) Increased ethanol drinking after repeated chronic ethanol exposure and withdrawal experience in C57BL/6 mice. Alcohol Clin Exp Res 28:1829-38. [Crossref]

  • Griffin WC, III, Lopez MF, Becker HC (2009) Intensity and duration of chronic ethanol exposure is critical for subsequent escalation of voluntary ethanol drinking in mice. Alcohol Clin Exp Res 33:1893-900. [Crossref] [Web of Science]

  • Becker HC (2012) Animal models of excessive alcohol consumption. Curr Top Behav Neurosci Feb 28, Epub ahead of print. [Crossref]

  • Lopez MF, Grahame NJ, Becker HC. (2011). Development of ethanol withdrawal-related sensitization and relapse drinking in mice selected for high- or low-ethanol preference. Alcohol Clin Exp Res 35:953-62. [Web of Science] [PubMed] [Crossref]

  • Metten P, Sorensen ML, Cameron AJ, Yu C-H, Crabbe JC. (2010). Withdrawal severity after chronic intermittent ethanol in inbred mouse strains. Alcohol Clin Exp Res 34:1552-64. [Crossref] [PubMed]

  • Crabbe JC, Spence SE, Brown LL, Metten P. (2011). Alcohol preference drinking in a mouse line selectively bred for high drinking in the dark. Alcohol 45:427-40. [Crossref]

  • Crabbe JC, Phillips TJ, Kosobud A, Belknap JK. (1990). Estimation of genetic correlation: interpretation of experiments using selectively bred and inbred animals. Alcohol Clin Exp Res 14:2:141-51. [Crossref] [PubMed]

  • Lopez MF, Becker HC. (2005). Effect of pattern and number of chronic ethanol exposures on subsequent voluntary ethanol intake in C57BL/6J mice. Psychopharmacology (Berl) 181:688-96.

  • Terdal ES, Crabbe JC. (1994). Indexing withdrawal in mice: matching genotypes for exposure in studies using ethanol vapor inhalation. Alcohol Clin Exp Res 18:542-7. [Crossref] [PubMed]

  • Metten P, Crabbe JC. (2005). Alcohol withdrawal severity in inbred mouse (Mus musculus) strains. Behav Neurosci 119:911-25. [PubMed] [Crossref]

  • Rustay NR, Crabbe JC. (2004). Genetic analysis of rapid tolerance to ethanol's incoordinating effects in mice: Inbred strains and artificial selection. Behav Genet 34:441-51. [Crossref]

  • Metten P, Brown LL, Crabbe JC. (2011). Limited access ethanol drinking in the dark in adolescent and adult mice. Pharmacol Biochem Behav 98:279-85. [PubMed] [Crossref] [Web of Science]

  • Yoneyama N, Crabbe JC, Ford MM, Murillo A, Finn DA. (2008). Voluntary ethanol consumption in 22 inbred mouse strains. Alcohol 42:149-60. [PubMed] [Crossref]

  • Belknap JK, Crabbe JC, Young ER. (1993). Voluntary consumption of ethanol in 15 inbred mouse strains. Psychopharmacology 112:503-10. [Crossref] [PubMed]

  • Crabbe JC, Colville AM, Kruse LC, Cameron AJ, Spence SE, Schlumbohm JP, et al. (2012). Ethanol tolerance and withdrawal severity in High Drinking in the Dark selectively bred mice. Alcohol Clin Exp Res 36:1152-61. [PubMed] [Crossref] [Web of Science]

  • Metten P, Phillips TJ, Crabbe JC, Tarantino LM, McClearn GE, Plomin R, Erwin VG, Belknap JK (1998). High genetic susceptibility to ethanol withdrawal predicts low ethanol consumption, Mammal Genome 9:9833-990.

  • Rosenwasser AM, Fixaris MC, Crabbe JC, Brooks PC, Ascheid S. (2012) Escalation of intake under intermittent ethanol access in diverse mouse genotypes. Addict Biol, epub ahead of print. [Web of Science]

  • Agrawal A, Freedman ND, Cheng YC, Lin P, Shaffer JR, Sun Q, et al. (2012). Measuring alcohol consumption for genomic meta-analyses of alcohol intake: opportunities and challenges. Am J Clin Nutr 95:539-47. [Web of Science] [PubMed] [Crossref]

  • Crabbe JC. (2012). Translational behaviour-genetic studies of alcohol: are we there yet? Genes Brain Behav 11:375-86. [PubMed] [Crossref] [Web of Science]

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