Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder.

Alcohol use disorder (AUD) is a chronic alcohol-related disorder that typically presents as uncontrolled drinking and preoccupation with alcohol. A key component of AUD research is using translationally relevant preclinical models. Over the past several decades, a variety of animal models have been used to study AUD. One prominent model of AUD is the chronic intermittent ethanol vapor exposure (CIE) model, which is a well-established approach for inducing alcohol dependence in rodents through repeated cycles of ethanol exposure via inhalation. To model AUD in mice, the CIE exposure is paired with a voluntary two-bottle choice (2BC) of alcohol drinking and water to measure the escalation of alcohol drinking. The 2BC/CIE procedure involves alternating weeks of 2BC drinking and CIE, which repeat until the escalation of alcohol drinking is achieved. In the present study, we outline the procedures for performing 2BC/CIE, including the daily use of the CIE vapor chamber, and provide an example of escalated alcohol drinking in C57BL/6J mice using this approach.

Prior experience with flavored alcohol increases preference for flavored alcohol but flavor does not influence binge-like drinking behavior in mice.

BACKGROUND: Binge drinking can lead to various negative consequences and in non-experimental settings, alcohol usually contains flavoring, which may promote increased binge drinking. Preclinical models of binge-like drinking have been well established, however, the influence of flavor on alcohol preference and binge-like drinking has not been fully explored. METHODS: Male and female C57BL/6 J mice were tested via two-bottle choice with alcohol flavored with different concentrations of unsweetened Cherry flavor Kool-Aid and water. Next, mice were tested for preference for flavored alcohol over plain alcohol. Consumption of flavored alcohol versus water was examined over 48 h. Binge-like drinking with flavored alcohol was validated via drinking in the dark (DID). A separate cohort of mice underwent chronic DID for 6 weeks with either flavored or plain alcohol. After chronic DID, mice were then tested for preference for flavored versus plain alcohol and then alcohol consumption despite adverse effects was examined using the quinine adulteration test. RESULTS: The 0.1% Kool-Aid concentration was chosen to use for further testing based on intake. Mice preferred Kool-Aid flavored alcohol over plain alcohol after the concentration test, but mice with no prior exposure to plain or flavored alcohol preferred plain over flavored alcohol. Throughout all initial testing, female mice showed increased alcohol intake compared to male mice. Both male and female mice showed binge-like drinking of flavored alcohol, with females having higher intake and blood alcohol levels. Kool-Aid flavor did not increase alcohol intake during chronic binge-like drinking. Previous exposure to flavored alcohol during DID increased the preference for flavored alcohol over plain alcohol but did not influence alcohol consumption despite adverse effects. CONCLUSION: The present study indicates that prior experience with flavored alcohol increases preference and intake, suggesting an effect of learned safety from neophobia. However, flavor does not impact binge-like alcohol consumption or alcohol drinking despite negative consequences. Additionally, the current study shows that female mice will consume more flavored alcohol than males, similar to findings from other alcohol studies.