Effect of alcohol withdrawal following binge-like drinking on nest building performance in mice

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André Borges, UNM Amanda Barkley-Levenson, UNM

Binge drinking is usually defined as the consumption of 5 or more drinks in one occasion for men and 4 or more for women. In the United States, roughly 24% of adults report weekly binge alcohol use, and 90% of adults who drink excessively report binge drinking. Binge drinking can lead to significant individual and societal costs and represents a serious public health concern. Additionally, binge drinking is associated with a higher risk of developing an alcohol use disorder and related problems such as alcohol withdrawal. Alcohol withdrawal symptoms can include negative affective changes including anxiety, depression, and agitation. Previous studies in mice have shown that alcohol withdrawal can cause lasting impairment in goal-directed behaviors such as nest building. Nest building deficits have been proposed as a novel measure of withdrawal severity following acute alcohol injection or vapor inhalation exposure. However, the effects of binge drinking on nest building have not been examined. In this study, we sought to determine whether a single binge alcohol exposure was sufficient to produce lasting deficits in nest building. Male and female C57BL/6J mice were tested for binge-like drinking using the drinking in the dark (DID) paradigm. In this paradigm, the animals had their water bottles replaced by an alcohol-containing tube in their active period for 2 hours a day during 3 days. On the fourth day, the drinking period was extended to four hours and the readings were done both after 2 and 4 hours. The animals were divided into 2 groups of 20 animals each, 10 males and 10 females. One of the groups had access to alcohol, whereas the other group was given water to serve as a control. At 24 hours and 6 days after the end of the DID, all animals were given a cotton nestlet square to produce their nests, which were then evaluated and scored at 48 hours and 7 days following the final drinking session. Mice received a single test in the open field apparatus on day 9 (5 days after DID) to assess locomotor and anxiety-like behavior. Our results showed that the alcohol group had significantly poorer nest scores than the water drinking group 7 days after the DID test, but the groups did not differ in nest quality at the 48 hours time point. Open-field testing showed no significant difference between the alcohol and water group either for distance traveled or time spent in the center, which indicates that the nest building deficit is likely not due to changes in anxiety-like behaviors or locomotor activity. These results show that a single binge alcohol exposure can produce lasting impairment in nest building, confirming our hypothesis. These also suggest that this behavior can be used for indexing alcohol withdrawal severity after binge-like drinking.