Relative Fluid Novelty Differentially Alters the Time Course of Limited-Access Ethanol and Water Intake in Selectively Bred High Alcohol Preferring Mice

There is increasing evidence that an organism’s genetic background has a great influence on its propensity to display binge ethanol-drinking behavior (Barkley-Levenson and Crabbe, 2013, Bauer and Ceballos, 2014, Chassin et al., 2002, Coon et al., 2014, Iancu et al., 2013, Rhodes et al., 2007, Watson et al., 2013). However, to date we know very little about how previous binge-drinking history, together with genetic background, might facilitate future binge-drinking behavior. Because binge-ethanol consumption leads to a myriad of detrimental acute and long-term health consequences including approximately half of the annual ethanol related deaths in the U.S. (Bouchery et al., 2011, Naimi et al., 2014), efforts to understand how repeated binge-ethanol consumption influences future binge-drinking in populations at risk for excessive ethanol intake are of utmost importance. Increases in the rate of binge-like ethanol consumption in mice with genetic predisposition for excessive ethanol intake (C57BL/6J; B6) were recently described (Linsenbardt and Boehm, 2014). In these studies, mice given 15 consecutive days of limited access ethanol dramatically increased their rate of ethanol consumption over the course of the study without obvious asymptote. Water consuming control mice completely lacked this ‘front-loading’ behavior. Furthermore, when controls were given access to ethanol for a single session following repeated daily access to water, ethanol was consumed at a rate consistent with the first ethanol access session in repeated ethanol access groups. Together these results suggest that the observed increases in the rate of binge-ethanol intake in this genetically predisposed population were born out of previous binge-ethanol drinking experience. However, as conclusions about the influence of genetic background/risk on ethanol drinking behavior drawn from one population of homozygous mice should be interpreted cautiously, the current experiments were conducted in a different population of high alcohol preferring mice, in part, to determine their generalizability. High Alcohol Preferring (HAP) mice, bred for preference for ethanol over water under free-access conditions, were subjected to identical procedures as those recently described in B6 mice (Linsenbardt and Boehm, 2014) to determine 1) if similar temporal alterations in limited-access ethanol drinking (i.e. front-loading) develop in a population selected for high ethanol preference/intake under continuous (24hr) access conditions, and 2) if any such temporal alterations might persist when given access to one of these two solutions for the first time. Because the development of behavioral and metabolic tolerance has been shown to develop following 2 weeks of limited access binge-like ethanol intake in B6 mice (Linsenbardt et al., 2011), and HAP mice have been shown to develop sensitization to the locomotor stimulant effects of experimenter administered ethanol (Grahame et al., 2000), a final goal was to determine the extent to which repeated ethanol access/consumption might have led to metabolic and/or behavioral (locomotor) alterations in these studies.