Home-Cage Sipper Devices Reveal Age and Sex Differences in Ethanol Consumption Patterns

Abstract Free-choice paradigms such as two-bottle choice (2BC) are commonly used to characterize ethanol consumption and preference of rodent models used to study alcohol use disorder (AUD). However, these assays are limited by low temporal resolution that misses finer patterns of drinking behavior, including circadian drinking patterns that are known to vary with age and sex and are affected in AUD pathogenesis. Modern, cost-effective tools are becoming widely available that could elucidate these patterns, including open-source, Arduino-based home-cage sipper devices. We hypothesized that adaptation of these home-cage sipper devices would uncover distinct age- and sex-related differences in temporal drinking patterns. To test this hypothesis, we used the sipper devices in a continuous 2BC paradigm using water and ethanol (10%; v/v) for 14 days to measure drinking patterns of male and female adolescent (3-week), young adult (6-week), and mature adult (18-week) C57BL/6J mice. Daily grams of fluid consumption were manually recorded at the beginning of the dark cycle, while home-cage sipper devices continuously recorded the number of sips. Consistent with prior studies, females consumed more ethanol than males, and adolescent mice consumed the most out of any age group. Correlation analyses of manually recorded fluid consumption versus home-cage sipper activity revealed a statistically significant prediction of fluid consumption across all experimental groups. Sipper activity was able to capture subtle circadian differences between experimental groups, as well as distinct individual variation in drinking behavior among animals. Blood ethanol concentrations were significantly correlated with sipper data, suggesting that home-cage sipper devices can accurately determine individual timing of ethanol consumption. Overall, our studies show that augmenting the 2BC drinking paradigm with automated home-cage sipper devices can accurately measure ethanol consumption across sexes and age groups, revealing individual differences and temporal patterns of ethanol drinking behavior. Future studies utilizing these home-cage sipper devices will further dissect circadian patterns for age and sex relevant to the pathogenesis of AUD, as well as underlying molecular mechanisms for patterns in ethanol consumption. Highlights Female mice consume more ethanol than males in a continuous access paradigm Adolescent male and female mice consume more ethanol than young or mature adult mice Automated home-cage sipper devices accurately measure ethanol consumption Devices reveal sex- and age-dependent differences in circadian drinking patterns Devices reveal distinct individual variation in circadian drinking patterns