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Derivation and Characterization of Replicate High- and Low-Alcohol Preferring Lines of Mice and a High-Drinking Crossed HAP Line

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Abstract

Selectively breeding lines of mice and rats to differ in alcohol intake has proven useful for defining which traits correlate with high alcohol drinking behavior, as well as for creating animal models of alcoholism. This study reports the derivation of two novel sets of selected lines, High Alcohol Preferring (HAP) and Low Alcohol Preferring (LAP) replicate 2 and 3 lines. Mice were mass-selected using the same procedure as in the replicate 1 lines: using HS/Ibg as a progenitor, mice were selected for differences in 2-bottle choice intake of 10% alcohol during a 4-week testing period. In addition, another high-drinking line, the crossed HAP (cHAP) line was selectively bred from a progenitors that were a cross of replicate 1 (S27) × replicate 2 (S21) HAP lines. All lines were characterized for saccharin intake. Overall, the response to selection of the HAP and LAP replicate 2 and 3 lines was quite similar. As anticipated, following selection, the cHAP line drank more than either parent HAP line (consuming 26.0 g/kg per day of alcohol by S11), suggesting that this method of crossing replicate lines and selecting from that cross captures more alleles than any single selected line, as well as producing a line with exceptionally high voluntary alcohol intake. As expected, saccharin consumption was highly associated with alcohol consumption; data from 7 lines (HAP 1, 2, and 3, LAP 1, 2, and 3, and cHAP) indicated a genetic correlation between 10% alcohol and 0.32% saccharin intake of 0.91. Overall, these findings show the practicality of developing replicate lines divergent in alcohol preference, and validate a novel procedure for generating very high-drinking mouse populations.

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References

  • Agabio R, Carai MA et al (2000) Dissociation of ethanol and saccharin preference in sP and sNP rats. Alcohol Clin Exp Res 24(1):24–29

    Article  PubMed  Google Scholar 

  • Belknap JK, Crabbe JC et al (1993) Voluntary consumption of ethanol in 15 inbred mouse strains. Psychopharmacology 112(4):503–510

    Article  PubMed  Google Scholar 

  • Belknap JK, Richards SP et al (1997) Short-term selective breeding as a tool for QTL mapping: ethanol preference drinking in mice. Behav Genet 27(1):55–66

    Article  PubMed  Google Scholar 

  • Bice PJ, Foroud T et al (2006) Identification of QTLs influencing alcohol preference in the High Alcohol Preferring (HAP) and Low Alcohol Preferring (LAP) mouse lines. Behav Genet 36(2):248–260

    Article  PubMed  Google Scholar 

  • Bice P, Valdar W et al (2009) Genomewide SNP screen to detect quantitative trait Loci for alcohol preference in the high alcohol preferring and low alcohol preferring mice. Alcohol Clin Exp Res 33(3):531–537

    Article  PubMed  Google Scholar 

  • Blednov YA, Metten P et al (2005) Hybrid C57BL/6J × FVB/NJ mice drink more alcohol than do C57BL/6J mice. Alcohol Clin Exp Res 29(11):1949–1958

    Article  PubMed  Google Scholar 

  • Blednov YA, Ozburn AR et al (2010) Hybrid mice as genetic models of high alcohol consumption. Behav Genet 40(1):93–110

    Article  PubMed  Google Scholar 

  • Carroll ME, Morgan AD et al (2008) Selective breeding for differential saccharin intake as an animal model of drug abuse. Behav Pharmacol 19(5–6):435–460

    Article  PubMed  Google Scholar 

  • Chester JA, Lumeng L et al (2003) High- and low-alcohol-preferring mice show differences in conditioned taste aversion to alcohol. Alcohol Clin Exp Res 27(1):12–18

    PubMed  Google Scholar 

  • Colombo G (1997) ESBRA-Nordmann 1996 Award Lecture: ethanol drinking behaviour in Sardinian alcohol-preferring rats. Alcohol Alcohol 32(4):443–453

    PubMed  Google Scholar 

  • Crabbe JC (1989) Genetic animal models in the study of alcoholism. Alcohol Clin Exp Res 13(1):120–127

    Article  PubMed  Google Scholar 

  • Crabbe JC, Phillips TJ et al (1990) Estimation of genetic correlation: interpretation of experiments using selectively bred and inbred animals. Alcohol Clin Exp Res 14(2):141–151

    Article  PubMed  Google Scholar 

  • Crabbe JC, Metten P et al (2009) A line of mice selected for high blood ethanol concentrations shows drinking in the dark to intoxication. Biol Psychiatry 65(8):662–670

    Article  PubMed  Google Scholar 

  • Crawley JN (2007) What’s wrong with my mouse? Behavioral phenotyping of transgenic and knockout mice. Wiley-Interscience, Hoboken, NJ

    Google Scholar 

  • Dess NK, Badia-Elder NE et al (1998) Ethanol consumption in rats selectively bred for differential saccharin intake. Alcohol 16(4):275–278

    Article  PubMed  Google Scholar 

  • Eriksson K (1968) Ethyl alcohol consumption: valid measurement in albino rats. Science 161(836):76–77

    Article  PubMed  Google Scholar 

  • Falconer DS, Mackay TFC (1996) Introduction to quantitative genetics. Addison Wesley Longman, Essex

    Google Scholar 

  • Flint J, Valdar W et al (2005) Strategies for mapping and cloning quantitative trait genes in rodents. Nat Rev Genet 6(4):271–286

    Article  PubMed  Google Scholar 

  • Foroud T, Bice P et al (2002) Mapping of QTL influencing saccharin consumption in the selectively bred alcohol-preferring and -nonpreferring rat lines. Behav Genet 32(1):57–67

    Article  PubMed  Google Scholar 

  • Goldman D, Oroszi G et al (2005) The genetics of addictions: uncovering the genes. Nat Rev Genet 6(7):521–532

    Article  PubMed  Google Scholar 

  • Grahame NJ (2000) Selected lines and inbred strains. Tools in the hunt for the genes involved in alcoholism. Alcohol Res Health 24(3):159–163

    PubMed  Google Scholar 

  • Grahame NJ, Li TK et al (1999) Selective breeding for high and low alcohol preference in mice. Behav Genet 29(1):47–57

    Article  PubMed  Google Scholar 

  • Green AS, Grahame NJ (2008) Ethanol drinking in rodents: is free-choice drinking related to the reinforcing effects of ethanol? Alcohol 42(1):1–11

    Article  PubMed  Google Scholar 

  • Grisel JE, Metten P et al (2002) Mapping of quantitative trait loci underlying ethanol metabolism in BXD recombinant inbred mouse strains. Alcohol Clin Exp Res 26(5):610–616

    Article  PubMed  Google Scholar 

  • Jacquot C, Croft AP et al (2008) “Effects of the glucocorticoid antagonist, mifepristone, on the consequences of withdrawal from long term alcohol consumption. Alc Clin Exp Res 32(12):2107–2116

    Article  Google Scholar 

  • Kampov-Polevoy AB, Kasheffskaya OP et al (1996) Pain sensitivity and saccharin intake in alcohol-preferring and -nonpreferring rat strains. Physiol Behav 59(4–5):683–688

    Article  PubMed  Google Scholar 

  • Kampov-Polevoy A, Garbutt JC et al (1997) Evidence of preference for a high-concentration sucrose solution in alcoholic men. Am J Psychiatry 154(2):269–270

    PubMed  Google Scholar 

  • Kampov-Polevoy AB, Garbutt JC et al (1999) Association between preference for sweets and excessive alcohol intake: a review of animal and human studies. Alcohol Alcohol 34(3):386–395

    PubMed  Google Scholar 

  • Kranzler HR, Sandstrom KA et al (2001) Sweet taste preference as a risk factor for alcohol dependence. Am J Psychiatry 158(5):813–815

    Article  PubMed  Google Scholar 

  • Le AD, Israel Y et al (2001) Genetic selection for high and low alcohol consumption in a limited-access paradigm. Alcohol Clin Exp Res 25(11):1613–1620

    Article  PubMed  Google Scholar 

  • Li TK, Lumeng L et al (1993) Selective breeding for alcohol preference and associated responses. Behav Genet 23(2):163–170

    Article  PubMed  Google Scholar 

  • Lu K, McDaniel AH, Tordoff MG et al (2005) “No relationship between sequence variation in protein coding regions of the Tas1r3 gene and saccharin preference in rats. Chem Senses 30(3):231–240

    Article  PubMed  Google Scholar 

  • Lumeng L, Hawkins TD et al (1977) Alcohol and aldehyde metabolizing systems. Academic Press, New York

    Google Scholar 

  • Mardones J, Segovia-Riquelme N (1983) Thirty-two years of selection of rats by ethanol preference: UChA and UChB strains. Neurobehav Toxicol Teratol 5(2):171–178

    PubMed  Google Scholar 

  • Mennella JA, Pepino MY et al (2010) Sweet preferences and analgesia during childhood: effects of family history of alcoholism and depression. Addiction 105(4):666–675

    Article  PubMed  Google Scholar 

  • Murphy JM, Stewart RB et al (2002) Phenotypic and genotypic characterization of the Indiana University rat lines selectively bred for high and low alcohol preference. Behav Genet 32(5):363–388

    Article  PubMed  Google Scholar 

  • Oberlin BG, Grahame NJ (2009) High alcohol preferring mice are more impulsive than low alcohol preferring mice as measured in the delay discounting task. Alcohol Clin Exp Res 33(7):1–10

    Article  Google Scholar 

  • Phillips TJ, Crabbe JC et al (1994) Localization of genes affecting alcohol drinking in mice. Alcohol Clin Exp Res 18(4):931–941

    Article  PubMed  Google Scholar 

  • Phillips TJ, Shen EH et al (2002) Forward, relaxed, and reverse selection for reduced and enhanced sensitivity to ethanol’s locomotor stimulant effects in mice. Alcohol Clin Exp Res 26(5):593–602

    PubMed  Google Scholar 

  • Rodriguez LA, Plomin R et al (1995) Alcohol acceptance, preference, and sensitivity in mice. II. Quantitative trait loci mapping analysis using BXD recombinant inbred strains. Alcohol Clin Exp Res 19(2):367–373

    Article  PubMed  Google Scholar 

  • Sinclair JD, Kampov-Polevoy A et al (1992) Taste preferences in rat lines selected for low and high alcohol consumption. Alcohol 9(2):155–160

    Article  PubMed  Google Scholar 

  • Stewart RB, Russell RN et al (1994) Consumption of sweet, salty, sour, and bitter solutions by selectively bred alcohol-preferring and alcohol-nonpreferring lines of rats. Alcohol Clin Exp Res 18(2):375–381

    Article  PubMed  Google Scholar 

  • Tampier L, Quintanilla ME (2005) Saccharin consumption and the effect of a long-term exposure to a sweetened alcoholic solution in high- (UChB) and low- (UChA) alcohol-drinking rats. Alcohol 37(1):47–52

    Article  PubMed  Google Scholar 

  • Tremblay KA, Bona JM et al (2009) Effects of a diagnosis or family history of alcoholism on the taste intensity and hedonic value of sucrose. Am J Addict 18(6):494–499

    Article  PubMed  Google Scholar 

  • Waller MB, McBride WJ et al (1982) Induction of dependence on ethanol by free-choice drinking in alcohol-preferring rats. Pharmacol Biochem Behav 16(3):501–507

    Article  PubMed  Google Scholar 

  • Waller MB, McBride WJ et al (1983) Initial sensitivity and acute tolerance to ethanol in the P and NP lines of rats. Pharmacol Biochem Behav 19(4):683–686

    Article  PubMed  Google Scholar 

  • Yoneyama N, Crabbe JC et al (2008) Voluntary ethanol consumption in 22 inbred mouse strains. Alcohol 42(3):149–160

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Indiana Alcohol Research Center (P60 07611) to David Crabb, U01 AA13483 to NJG, and F31 AA016430 to BGO. Thanks are also extended to Lawrence Lumeng, who initiated selection of replicate 1 HAP and LAP mice.

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Authors and Affiliations

  1. Department of Psychology, Indiana University Purdue University at Indianapolis, 402 N. Blackford St. LD120F, Indianapolis, IN, 46202, USA

    Brandon Oberlin, Christina Best, Liana Matson, Angela Henderson & Nicholas Grahame

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  1. Brandon Oberlin
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  2. Christina Best
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  3. Liana Matson
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  4. Angela Henderson
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  5. Nicholas Grahame
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Correspondence to Nicholas Grahame.

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Edited by Tamara Phillips.

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Oberlin, B., Best, C., Matson, L. et al. Derivation and Characterization of Replicate High- and Low-Alcohol Preferring Lines of Mice and a High-Drinking Crossed HAP Line. Behav Genet 41, 288–302 (2011). https://doi.org/10.1007/s10519-010-9394-5

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