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Abstract
Because of intrinsic differences between humans and mice, no single mouse model can
represent all features of a complex human trait such as alcoholism. It is therefore
necessary to develop partial models. One important feature is drinking to the point
where blood ethanol concentration (BEC) reaches levels that have measurable affects
on physiology and/or behavior (>1.0 mg ethanol/ml blood). Most models currently in
use examine relative oral self-administration from a bottle containing alcohol versus
one containing water (two-bottle preference drinking), or oral operant self-administration.
In these procedures, it is not clear when or if the animals drink to pharmacologically
significant levels because the drinking is episodic and often occurs over a 24-h period.
The aim of this study was to identify the optimal parameters and evaluate the reliability
of a very simple procedure, taking advantage of a mouse genotype (C57BL/6J) that is
known to drink large quantities of ethanol. We exchanged for the water bottle a solution
containing ethanol in tap water for a limited period, early in the dark cycle, in
the home cage. Mice regularly drank sufficient ethanol to achieve BEC>1.0 mg ethanol/ml
blood. The concentration of ethanol offered (10%, 20% or 30%) did not affect consumption
in g ethanol/kg body weight. The highest average BEC ( approximately 1.6 mg/ml) occurred
when the water-to-ethanol switch occurred 3 h into the dark cycle, and when the ethanol
was offered for 4 rather than 2 h. Ethanol consumption was consistent within individual
mice, and reliably predicted BEC after the period of ethanol access. C57BL/6J mice
from three sources provided equivalent data, while DBA/2J mice drank much less than
C57BL/6J in this test. We discuss advantages of the model for high-throughput screening
assays where the goal is to find other genotypes of mice that drink excessively, or
to screen drugs for their efficacy in blocking excessive drinking.