Voluntary ethanol consumption in 22 inbred mouse strains

Abstract

Inbred strains are genetically stable across time and laboratories, allowing scientists to accumulate a record of phenotypes, including physiological characteristics and behaviors. To date, the C57/C58 family of inbred mouse strains has been identified as having the highest innate ethanol consumption, but some lineages have rarely or never been surveyed. Thus, the purpose of the present experiment was to measure ethanol preference and intake in 22 inbred mouse strains, some of which have never been tested for ethanol consumption. Male and female mice (A/J, BALB/cByJ, BTBR+T tf/tf , BUB/ BnJ, C57BL/6J, C57BLKS/J, C58/J, CZECH/Ei, DBA/2J, FVB/NJ, I/LnJ, LP/J, MA/MyJ, NOD/ LtJ, NON/LtJ, NZB/B1NJ, NZW/LacJ, PERA/Ei, RIIIS/J, SEA/GnJ, SM/J, and 129S1/SvlmJ) were individually housed and given unlimited access in a two-bottle choice procedure to one bottle containing tap water and a second containing increasing concentrations of ethanol (3%, 6%, 10%), 0.2% saccharin, and then increasing concentrations of ethanol (3%, 6%, 10%) plus 0.2% saccharin. Mice were given access to each novel solution for a total of 4 days, with a bottle side change every other day. Consistent with previous studies, C57BL/6J (B6) mice consumed an ethanol dose of > 10g/kg/day while DBA/2J (D2) mice consumed < 2g/kg/day. No strain voluntarily consumed greater doses of ethanol than B6 mice. While the C58 and C57BLKS strains showed high ethanol consumption levels that were comparable to B6 mice, the BUB and BTBR strains exhibited low ethanol intakes similar to D2 mice. The addition of 0.2% saccharin to the ethanol solutions significantly increased ethanol intake by most strains and altered the strain distribution pattern. Strong positive correlations (rs ≥ 0.83) were determined between consumption of the unsweetened versus sweetened ethanol solutions. Consumption of saccharin alone was significantly positively correlated with the sweetened ethanol solutions (rs = 0.62 -0.81), but the correlation with unsweetened ethanol solutions was considerably lower (rs = 0.37 -0.45). These results add new strains to the strain mean database that will facilitate the identification of genetic relationships between voluntary ethanol consumption, saccharin preference, and other phenotypes.

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

“…Across the 3 available data sets [4,21,22], the strain mean correlation between g/kg intake and preference ratio (the proportion of total daily fluid ingested from the ethanol bottle) was r = 0.88 across these 41 strains. Since we believe g/kg intake to be the superior index of avidity for ethanol solutions (as it depends less on the concentration of ethanol offered than does the preference ratio), we correlated the g/kg intake from the two-bottle tests with g/kg intake from the DID test, as well as the BEC after DID.…”

“…On the other hand, we had previously compared S13 HDID-1 and G64 HS mice for two bottle preference drinking using a protocol very similar to those employed for the inbred strain studies [4,21,22]. 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].…”

“…Yoneyama [21] tested 22 inbred strains (8-10 weeks old) for 4 days each of 3%, then 6%, then 10% ethanol vs water. Belknap [22] used the same increasing series of ethanol concentrations but for only 3 days at each concentration in a test of 15 inbred strains aged 9-11 weeks.…”

The Role of Delta Opioid Receptors in Ethanol Consumption and Seeking: Implications for New Treatments for Alcohol Use Disorders

“…Although one study using purebred C57BL/6 mice failed to show any difference in ethanol intake (van Rijn & Whistler, 2009), the differences in these studies may reflect the varying degrees of ethanol intake in mice with different genetic backgrounds (Yoneyama et al, 2008) and also the models of ethanol consumption employed.…”

Pharmacologically Counteracting a Phenotypic Difference in Cerebellar GABAA Receptor Response to Alcohol Prevents Excessive Alcohol Consumption in a High Alcohol-Consuming Rodent Genotype

“…We recently determined that physiologically relevant concentrations of etha-nol (9 -52 mM) differentially affect granule cell (GC) tonic GABA A receptor (GABA A R) currents, as a function of ethanol consumption phenotype Mohr et al, 2013). Specifically, ethanol enhances tonic GABA A R-mediated inhibition in low ethanol-consuming rodent genotypes, including DBA/2J (D2) mice, but suppresses it in high ethanol-consuming C57BL/6J (B6) mice .…”