Three Weeks of Binge Alcohol Drinking Generates Increased Alcohol Front‐Loading and Robust Compulsive‐Like Alcohol Drinking in Male and Female C57BL/6J Mice

• Published in: Alcoholism, clinical and experimental research Vol. 45; no. 3; pp. 650 - 660
• Main Authors: Bauer, Meredith R., McVey, Megan M., Boehm, Stephen L.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-03-2021
• Subjects: Alcohol; Alcohol use; Alcoholism; Animal models; Aversion‐Resistant; Binge; Blood levels; Compulsion; Drinking behavior; Drinking water; Gender differences; Quinine; Sex differences; Alcohol; Aversion-Resistant; Quinine; Binge; Compulsion
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.14563

Background
Current models of compulsive‐like quinine‐adulterated alcohol (QuA) drinking in mice, if improved, could be more useful for uncovering the neural mechanisms of compulsive‐like alcohol drinking. The purpose of these experiments was to further characterize and improve the validity of a model of compulsive‐like QuA drinking in C57BL/6J mice. We sought to determine whether compulsive‐like alcohol drinking could be achieved following 2 or 3 weeks of Drinking‐in‐the‐Dark (DID), whether it provides evidence for a robust model of compulsive‐like alcohol drinking by inclusion of a water control group and use of a highly concentrated QuA solution, whether repeated QuA exposures alter compulsive‐like drinking, and whether there are sex differences in compulsive‐like alcohol drinking.
Methods
Male and Female C57BL/6J mice were allowed free access to either 20% alcohol or tap water for 2 hours each day for approximately 3 weeks. After 2 or 3 weeks, the mice were given QuA (500 μM) and the effect of repeated QuA drinking sessions on compulsive‐like alcohol drinking was assessed. 3‐minute front‐loading, 2 hour binge‐drinking, and blood alcohol concentrations were determined.
Results
Compulsive‐like QuA drinking was achieved after 3 weeks, but not 2 weeks, of daily alcohol access as determined by alcohol history mice consuming significantly more QuA than water history mice and drinking statistically nondifferent amounts of QuA than nonadulterated alcohol at baseline. Thirty‐minute front‐loading of QuA revealed that alcohol history mice front‐loaded significantly more QuA than water history mice, but still found the QuA solution aversive. Repeated QuA exposures did not alter these patterns, compulsive‐like drinking did not differ by sex, and BACs for QuA drinking were at the level of a binge.
Conclusions
These data suggest that compulsive‐like QuA drinking can be robustly achieved following 3 weeks of DID and male and female C57BL/6J mice do not differ in compulsive‐like alcohol drinking.
Compulsive‐like quinine‐adulterated alcohol (QuA) drinking models vary widely, commonly using relatively low quinine concentrations, excluding female mice, and excluding alcohol naïve control groups. We sought to define robust compulsive‐like QuA drinking in C57BL/6J mice. Compulsive‐like QuA drinking was achieved after 3‐weeks of daily Drinking‐in‐the‐Dark, as compulsive‐like alcohol history mice consumed more QuA than naïve mice and did not differ in QuA intakes from baseline. Repeated QuA exposures did not alter these patterns and compulsive‐like drinking did not differ by sex.