, Volume 178, Issue 4, pp 471–480 | Cite as

A procedure to produce high alcohol intake in mice

  • Deborah A. Finn
  • John K. Belknap
  • Kim Cronise
  • Naomi Yoneyama
  • Andrea Murillo
  • John C. Crabbe
Original Investigation



While prolonged access to ethanol (EtOH), or deprivations, or their combination have occasionally been shown to yield high levels of voluntary self-administration, in almost all cases, rodents do not self-administer alcohol to the degree that they will develop substantial, intoxicating blood alcohol levels and then continue to self-administer at these levels.


The purpose of the present series of experiments was to modify a fluid restriction procedure to demonstrate consistent, high EtOH consumption.


Male and female mice from an alcohol preferring inbred strain (C57BL/6J; B6) as well as from a genetically heterogeneous strain (WSC) were given varying periods of access to fluid, ranging from 90 min to 10 h per day, for 12–21 days. Every 3rd or 4th day, separate groups of mice were offered a 5, 7 or 10% EtOH solution for either 10 min or 30 min, followed by water for the remainder of the time.


In all studies, stable high EtOH doses were consumed by both B6 and WSC mice across the EtOH sessions, exceeding 2 g/kg in a 30-min session. Mean blood EtOH concentration exceeded 1 mg/ml (i.e. 100 mg%), with values in individual animals ranging from 0.6 mg/ml to 3.4 mg/ml. Notably, mice receiving 10 h of fluid/day continued to consume 2 g/kg doses of EtOH. While this procedure did not produce subsequent preference for EtOH in WSC mice, consumption remained high in some animals.


These data indicate that scheduling fluid intake produces high, stable EtOH consumption and BEC in male and female B6 and WSC mice.


Ethanol consumption Genetically heterogeneous mice C57BL/6 Blood ethanol concentration Intoxication 


  1. Belknap JK, Coleman RR, Foster K (1978) Alcohol consumption and sensory threshold differences between C57BL/6J and DBA/2J mice. Physiol Psychol 6:71–74Google Scholar
  2. Crabbe JC (2002) Alcohol and genetics: new models. Am J Med Genet 114:969–974CrossRefPubMedGoogle Scholar
  3. Crabbe JC, Gallaher ES, Phillips TJ, Belknap JK (1994) Genetic determinants of sensitivity to ethanol in inbred mice. Behav Neurosci 108:186–195CrossRefPubMedGoogle Scholar
  4. Cunningham CL, Fidler TL, Hill KG (2000) Animal models of alcohol’s motivational effects. Alcohol Res Health 24:85–92PubMedGoogle Scholar
  5. Dole VP, Gentry RT (1984) Toward an analogue of alcoholism in mice: scale factors in the model. Proc Natl Acad Sci USA 81:3543–3546PubMedGoogle Scholar
  6. Elmer GI, Meisch RA, George FR (1986) Oral ethanol reinforced behavior in inbred mice. Pharmacol Biochem Behav 24:1417–1421CrossRefPubMedGoogle Scholar
  7. Elmer GI, Meisch RA, George FR (1987) Differential concentration-response curves for oral ethanol self-administration in C57BL/6J and BALB/cJ mice. Alcohol 4:63–68CrossRefPubMedGoogle Scholar
  8. Falk JL (1961) Production of polydipsia in normal rats by an intermittent food schedule. Science 133:195–196PubMedGoogle Scholar
  9. Falk JL, Tang M (1988) What schedule-induced polydipsia can tell us about alcoholism. Alcohol Clin Exp Res 12:577–585PubMedGoogle Scholar
  10. Falk JL, Samson HH, Winger G (1972) Behavioral maintenance of high concentrations of blood ethanol and physical dependence in the rat. Science 177:811–813PubMedGoogle Scholar
  11. Finn DA, Sinnott RS, Ford MM, Long SL, Tanchuck MA, Phillips TJ (2004) Sex differences in the effect of ethanol injection and consumption on brain allopregnanolone levels in C57BL/6 mice. Neuroscience 123:813–819CrossRefPubMedGoogle Scholar
  12. Freund G (1969) Alcohol withdrawal syndrome in mice. Arch Neurol 21:315–320PubMedGoogle Scholar
  13. Grahame NJ, Grose AM (2003) Blood alcohol concentrations after scheduled access in high-alcohol-preferring mice. Alcohol 21:99–104CrossRefGoogle Scholar
  14. Grahame NJ, Li T-K, Lumeng L (1999) Limited access alcohol drinking in high- and low-alcohol preferring selected lines of mice. Alcohol Clin Exp Res 23:1015–1022CrossRefPubMedGoogle Scholar
  15. Gray GD, Bergfors AM, Levin R, Levine S (1978) Comparison of the effects of restricted morning or evening water intake on adrenocortical activity in female rats. Neuroendocrinology 25:236–246PubMedGoogle Scholar
  16. Heiderstadt KM, McLaughlin RM, Wright DC, Walker SE, Gomez-Sanchez CE (2000) The effect of chronic food and water restriction on open-field behaviour and serum corticosterone levels in rats. Lab Anim 34:20–26PubMedGoogle Scholar
  17. Hölter SM, Linthorst ACE, Reul JMHM, Spanagel R (2000) Withdrawal symptoms in a long-term model of voluntary alcohol drinking in Wistar rats. Pharmacol Biochem Behav 66:143–151CrossRefPubMedGoogle Scholar
  18. Hughes JE, Amyz H, Howard JL, Nanry KP, Pollard GT (1994) Health effects of water restriction to motivate lever-pressing in rats. Lab Anim Sci 44:135–140PubMedGoogle Scholar
  19. Johnson JT, Levine S (1973) Influence of water deprivation on adrenocortical rhythms. Neuroendocrinology 11:268–273PubMedGoogle Scholar
  20. Lê AD, Ko J, Chow S, Quan B (1994) Alcohol consumption by C57BL/6, BALB/c, and DBA/2 mice in a limited access paradigm. Pharmacol Biochem Behav 47:375–378CrossRefPubMedGoogle Scholar
  21. Lester D (1961) Self-maintenance of intoxication in the rat. Q J Stud Alcohol 122:223–231Google Scholar
  22. Li T-K, Lumeng L, Doolittle DP (1993) Selective breeding for alcohol preference and associated responses. Behav Genet 23:163–170PubMedGoogle Scholar
  23. McBride WJ, Li T-K (1998) Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents. Crit Rev Neurobiol 12:339–369PubMedGoogle Scholar
  24. McClearn GE (1979) Genetics and alcoholism simulacra. Alcohol Clin Exp Res 3:255–258PubMedGoogle Scholar
  25. Middaugh LD, Kelley BM (1999) Operant ethanol reward in C57BL/6 mice: influence of gender and procedural variables. Alcohol 17:185–194CrossRefPubMedGoogle Scholar
  26. Middaugh LD, Kelley BM, Bandy A-LE, McGroarty KK (1999) Ethanol consumption by C57BL/6 mice: influence of gender and procedural variables. Alcohol 17:175–183CrossRefPubMedGoogle Scholar
  27. Middaugh LD, Szumlinski KK, Van Patten Y, Marlowe A-LB, Kalivas PW (2003) Chronic ethanol consumption by C57BL/6 mice promotes tolerance to its interoceptive cues and increases extracellular dopamine, an effect blocked by naltrexone. Alcohol Clin Exp Res 27:1892–1900CrossRefPubMedGoogle Scholar
  28. Mittleman G, Van Brunt CL, Matthews DB (2003) Schedule-induced ethanol self-administration in DBA/2J and C57BL/6J mice. Alcohol Clin Exp Res 27:918–925CrossRefPubMedGoogle Scholar
  29. Murphy JM, Gatto GJ, Waller MB, McBride WJ, Lumeng L, Li T-K (1986) Effects of scheduled access on ethanol intake by the alcohol-preferring (P) line of rats. Alcohol 3:331–336CrossRefPubMedGoogle Scholar
  30. Ogata H, Ogato F, Mendelson JH, Mello NK (1972) A comparison of techniques to induce alcohol dependence and tolerance in the mouse. J Pharmacol Exp Ther 180:216–230PubMedGoogle Scholar
  31. Risinger FO, Brown MM, Doan AM, Oakes RA (1998) Mouse strain differences in oral operant ethanol reinforcement under continuous access conditions. Alcohol Clin Exp Res 22:677–684PubMedGoogle Scholar
  32. Roach M, Creaven P (1968) A micro-method for the determination of acetaldehyde and ethanol in blood. Clin Chim Acta 21:275–278CrossRefPubMedGoogle Scholar
  33. Roberts AJ, Heyser CJ, Cole M, Griffin P, Koob GF (2000a) Excessive ethanol drinking following a history of dependence: animal model of allostasis. Neuropsychopharmacology 22:581–594CrossRefPubMedGoogle Scholar
  34. Roberts AJ, McDonald JS, Heyser CJ, Kieffer BL, Matthes HW, Koob GF, Gold LH (2000b) Mu-opioid receptor knockout mice do not self-administer alcohol. J Pharmacol Exp Ther 293:1002–1008PubMedGoogle Scholar
  35. Rodd ZA, Bell RL, Kuc KA, Murphy JM, Lumeng L, Li T-K, McBride WJ (2003) Effects of repeated alcohol deprivations on operant ethanol self-administration by alcohol-preferring (P) rats. Neuropsychopharmacology 28:1614–1621CrossRefPubMedGoogle Scholar
  36. Rodd-Hendricks ZA, Bell RL, Kuc KA, Murphy JM, McBride WJ, Lumeng L, Li T-K (2001) Effects of concurrent access to multiple ethanol concentrations and repeated deprivations on alcohol intake of alcohol-preferring rats. Alcohol Clin Exp Res 25:1140–1150CrossRefPubMedGoogle Scholar
  37. Rolls BJ, Wood RJ, Rolls ET (1980) Thirst: the initiation, maintenance, and termination of drinking. Prog Psychobiol Physiol Psychol 9:263–321Google Scholar
  38. Samson HH (1986) Initation of ethanol reinforcement using a sucrose-substitution procedure in food- and water-sated rats. Alcohol Clin Exp Res 10:436–442PubMedGoogle Scholar
  39. Samson HH, Tolliver GA, Pfeffer AO, Sadeghi K, Haraguchi M (1988) Relation of ethanol self-administration to feeding and drinking in a nonrestricted access situation in rats initiated to self-administer ethanol using the sucrose-fading technique. Alcohol 5:375–385CrossRefPubMedGoogle Scholar
  40. Schulteis G, Hyytiiä, Heinrichs SC, Koob GF (1996) Effects of chronic ethanol exposure on oral self-administration of ethanol or saccharin by Wistar rats. Alcohol Clin Exp Res 20:164–171PubMedGoogle Scholar
  41. Serra S, Brunetti G, Vacca G, Lobina C, Carai MAM, Gessa GL, Colombo G (2003) Stable preference for high ethanol concentrations after ethanol deprivation in Sardinian alcohol-preferring (sP) rats. Alcohol 29:101–108CrossRefPubMedGoogle Scholar
  42. Toth LA, Gardiner TW (2000) Food and water restriction protocols: physiological and behavioral considerations. Contemp Top 39:9–17Google Scholar
  43. Vengeliene V, Siegmund S, Singer MV, Sinclair JD, Li T-K, Spanagel R (2003) A comparative study on alcohol-preferring rat lines: effects of deprivation and stress phases on voluntary alcohol intake. Alcohol Clin Exp Res 27:1048–1054PubMedGoogle Scholar
  44. Weiss F, Mitchiner M, Bloom FE, Koob GE (1990) Free-choice responding for ethanol versus water in alcohol-preferring (P) and unselected Wistar rats is differentially altered by naloxone, bromocriptine and methysergide. Psychopharmacology 101:178–186PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Deborah A. Finn
    • 1
  • John K. Belknap
    • 1
  • Kim Cronise
    • 1
  • Naomi Yoneyama
    • 1
  • Andrea Murillo
    • 1
  • John C. Crabbe
    • 1
  1. 1.Portland Alcohol Research Center, VAMC Research and Department of Behavioral NeuroscienceOregon Health & Science UniversityPortlandUSA

Personalised recommendations