Limited access ethanol drinking in the dark in adolescent and adult mice.

Portland Alcohol Research Center, Research Service, VA Medical Center, OR 97239, USA.
Pharmacology Biochemistry and Behavior (Impact Factor: 2.82). 04/2011; 98(2):279-85. DOI: 10.1016/j.pbb.2011.01.003
Source: PubMed

ABSTRACT Adult risk of alcohol dependence increases the younger one first engages in intoxicating consumption. Adolescent mice drink more ethanol than do adults on a gram per kilogram basis, an increase sometimes persisting into adulthood, and this is genotype-dependent. Most studies have used 24 h two-bottle preference, with a choice between ethanol and water. We studied the developmental onset of binge drinking using limited access ethanol drinking in the dark (DID) in male and female mice. To establish age dependence in DID magnitude, we tested HS/Npt mice of 6 ages for DID for 2 weeks, and when they were 9 weeks old, we retested them for 2 weeks vs naïve adult controls. Age groups drank equivalently in their first week; thus, adolescent HS/Npt mice do not show greater DID than adults. Six week old mice drank more ethanol during their second week relative to their other weeks. Ethanol DID during early adolescence (4 weeks) led to increased drinking in adulthood, as did initial DID exposure at 8 weeks. High drinking in the dark-1 (HDID-1) mice (4, 6, 9 weeks old), selectively bred for high blood ethanol after DID, were tested for 9 weeks. Mice beginning at 4 weeks generally drank more ethanol than those of other age groups. Comparison at the same ages showed that 9 week olds initiated at 4 weeks drank more ethanol than did naïve 9 week olds, but all three groups of age-matched mice drank equivalent amounts once they were 10 weeks and older. The DID test is thus sensitive to developmental age. DID intakes by young adolescent HDID-1 mice were greater than intakes by older mice, like those shown by studies with two-bottle preference. Early DID led to increased drinking as adults only in HS/Npt mice. HDID-1 mice provide a useful animal model for exploring whether DID and continuous access preference drinking have parallel consequences when initiated in adolescence.

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    ABSTRACT: This review provides an overview of an animal model of binge-like ethanol drinking that has come to be called "drinking in the dark" (DID), a procedure that promotes high levels of ethanol drinking and pharmacologically relevant blood ethanol concentrations (BECs) in ethanol-preferring strains of mice. Originally described by Rhodes, Best, Belknap, Finn, and Crabbe (2005), the most common variation of the DID procedure, using singly housed mice, involves replacing the water bottle with a bottle containing 20% ethanol for 2-4 h, beginning 3 h into the dark cycle. Using this procedure, high ethanol drinking strains of mice (e.g., C57BL/6J) typically consume enough ethanol to achieve BECs greater than 100 mg/dL and to exhibit behavioral evidence of intoxication. This limited access procedure takes advantage of the time in the animal's dark cycle in which the levels of ingestive behaviors are high, yet high ethanol intake does not appear to stem from caloric need. Mice have the choice of drinking or avoiding the ethanol solution, eliminating the stressful conditions that are inherent in other models of binge-like ethanol exposure in which ethanol is administered by the experimenter, and in some cases, potentially painful. The DID procedure is a high throughput approach that does not require extensive training or the inclusion of sweet compounds to motivate high levels of ethanol intake. The high throughput nature of the DID procedure makes it useful for rapid screening of pharmacological targets that are protective against binge-like drinking and for identifying strains of mice that exhibit binge-like drinking behavior. Additionally, the simplicity of DID procedures allows for easy integration into other paradigms, such as prenatal ethanol exposure and adolescent ethanol drinking. It is suggested that the DID model is a useful tool for studying the neurobiology and genetics underlying binge-like ethanol drinking, and may be useful for studying the transition to ethanol dependence.
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