Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice.
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.
Rhodes
Justin S
JS
Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health and Science University, and VA Medical Center, Portland, Oregon 97239, USA. rhodesju@ohsu.edu
Best
Karyn
K
Belknap
John K
JK
Finn
Deborah A
DA
Crabbe
John C
JC
D000428:Alcohol Drinking / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D000435:Alcoholic Intoxication / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal; D002492:Central Nervous System Depressants / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results; D013997:Time Factors
D002492:Central Nervous System Depressants; D000431:Ethanol