Alcohol preference drinking in a mouse line selectively bred for high drinking in the dark

Abstract

We have selectively bred mice that reach very high blood ethanol concentrations (BECs) after drinking from a single bottle of 20% ethanol. High Drinking in the Dark (HDID-1) mice drink nearly 6 g/kg ethanol in 4 hr and reach average BECs of more than 1.0 mg/ml. Previous studies suggest that DID and two-bottle preference for 10% ethanol with continuous access are influenced by many of the same genes. We therefore asked whether HDID-1 mice would differ from the HS/Npt control stock on two-bottle preference drinking. We serially offered mice access to 3 – 40% ethanol in tap water vs tap water. For ethanol concentrations between 3 and 20%, HDID-1 and HS/Npt controls did not differ in two-bottle preference drinking. At the highest concentrations, the HS/Npt mice drank more than the HDID-1 mice. We also tested the same mice for preference for two concentrations each of quinine, sucrose, and saccharin. Curiously, the mice showed preference ratios (volume of tastant / total fluid drunk) of about 50% for all tastants and concentrations. Thus, neither genotype showed either preference or avoidance for any tastant after high ethanol concentrations. Therefore, we compared naive groups of HDID-1 and HS/Npt mice for tastant preference. Results from this test showed that ethanol-naive mice preferred sweet fluids and avoided quinine but the genotypes did not differ. Finally, we tested HDID-1 and HS mice for an extended period for preference for 15% ethanol vs water during a 2 hr access period in the dark. After several weeks, HDID-1 mice consumed significantly more than HS. We conclude that Drinking in the Dark shows some genetic overlap with other tests of preference drinking, but that the degree of genetic commonality depends upon the model used.

Ethanol Withdrawal-Associated Drinking and Drinking in the Dark: Common and Discrete Genetic Contributions

“…1). We found a similar difference in the earlier study, although the difference emerged after some weeks of exposure [14]. A recent paper also reported a small difference between HDID-1 and HS mice in continuous-access preference for 10% ethanol vs water [25].…”

“…In that comparison, strains were offered 4 days each of choice between 3%, 6%, 9%, 12%, 15% ethanol versus water, and then higher concentrations [14]. HDID-1 mice tended to drink a little more ethanol than HS at the 9-15% concentrations, inclusive, but did not differ at lower concentrations, and, surprisingly, drank less ethanol than HS at concentrations ≥20%.…”

“…We have extensively discussed how we handle drinking data in DID and preference studies ([14,20] and see http://www.scripps.edu/california/research/inia/modelmousedrinkingindark.pdf). These discussions cover such topics as corrections for leakage, exclusion of outliers, and treatment of missing data.…”

“…Comparisons across 7 inbred strains for their mean intake data for DID and g/kg daily consumption in a two-bottle preference test have suggested a substantial degree of positive correlation for these two traits (r = 0.70, see [7]). A comparison of HDID-1 and the HS control mice from which they were bred on limited access two-bottle preference for 15% ethanol showed modestly (but significantly) greater drinking in HDID-1 than HS [14]. Little is known about the potential genetic overlap between ethanol DID and post-CIE drinking.…”

Chronic postnatal stress induces voluntary alcohol intake and modifies glutamate transporters in adolescent rats

“…The rats had free access to the drinking bottles, as in the two-bottle free choice method (Crabbe et al, 2011). At the end of 7 days with free access to ethanol or dextrose, the rats were killed.…”