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 6g/kg ethanol in 4h and reach average BECs of more than 1.0mg/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 versus 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 versus water during a 2-h 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 on the model used.
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ABSTRACT: We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predis-posed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses in HAP mice. Naïve male and female adult HAP mice from the second replicate of selection (HAP2) un-derwent 18 days of 24-h, 2-bottle choice drinking for 10% ethanol vs. water, or water only. After 18 days of fluid access, mice were tested for ataxic sensitivity and rapid AFT following a 1.75 g/kg injection of ethanol on a static dowel apparatus in Experiment 1. In Experiment 2, a separate group of mice was tested for more protracted AFT development using a dual-injection approach where a second, larger (2.0 g/kg) injection of ethanol was given following the initial recovery of performance on the task. HAP2 mice that had prior access to alcohol exhibited a blunted ataxic response to the acute alcohol challenge, but this pre-exposure did not alter rapid within-session AFT capacity in Experiment 1 or more protracted AFT capacity in Experiment 2. These findings suggest that the typically observed increase in alcohol consumption in these mice may be influenced by ataxic functional tolerance development, but is not mediated by a greater capacity for ethanol exposure to positively influence within-session ataxic tolerance.Alcohol 10/2014; DOI:10.1016/j.alcohol.2014.06.009 · 2.04 Impact Factor
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ABSTRACT: The orexin (OX) system has been implicated in food reinforced behaviour, food-seeking and food overconsumption. Recent evidence suggests that OX signaling might influence consumption of palatable foods with high reinforcing value depending upon the caloric status of the animal. The present study evaluates from a pharmacological and a molecular approach the contribution of OX to excessive binge-like consumption of highly preferred palatable substances (sucrose and saccharin) in ad libitum-fed C57BL/6J mice. The main findings in the study are: (1) intraperitoneal (ip) injection of SB-334867 (10, 20 or 30mg/kg), a selective OXR1 antagonist, significantly decreased binge-like consumption of sucrose (10% (w/v)) and saccharin (0.15% (w/v)) during the test day in a Drinking in the Dark procedure in ad libitum fed animals, without evidence of any significant alteration of locomotor activity. 2) 4 repetitive, 2-h daily episodes of sucrose and saccharin (but not water) binge-like drinking significantly dampened OX mRNA expression in the LH. Present findings show for the first time a role for OXR1 signaling in binge-like consumption of palatable substances in animals under no caloric needs. Targeting OXR1 could represent a novel pharmacological approach to treat binge-eating episodes.Behavioural Brain Research 06/2014; 272(1):93-99. DOI:10.1016/j.bbr.2014.06.049 · 3.39 Impact Factor
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ABSTRACT: The ILSXISS (LXS) recombinant inbred (RI) panel of mice is a valuable resource for genetic mapping studies of complex traits, due to its genetic diversity and large number of strains. Male and female mice from this panel were used to investigate genetic influences on alcohol consumption in the “drinking in the dark” (DID) model. Male mice (38 strains) and female mice (36 strains) were given access to 20 % ethanol during the early phase of their circadian dark cycle for four consecutive days. The first principal component of alcohol consumption measures on days 2, 3, and 4 was used as a phenotype (DID phenotype) to calculate QTLs, using a SNP marker set for the LXS RI panel. Five QTLs were identified, three of which included a significant genotype by sex interaction, i.e., a significant genotype effect in males and not females. To investigate candidate genes associated with the DID phenotype, data from brain microarray analysis (Affymetrix Mouse Exon 1.0 ST Arrays) of male LXS RI strains were combined with RNA-Seq data (mouse brain transcriptome reconstruction) from the parental ILS and ISS strains in order to identify expressed mouse brain transcripts. Candidate genes were determined based on common eQTL and DID phenotype QTL regions and correlation of transcript expression levels with the DID phenotype. The resulting candidate genes (in particular, Arntl/Bmal1) focused attention on the influence of circadian regulation on the variation in the DID phenotype in this population of mice.Mammalian Genome 01/2015; DOI:10.1007/s00335-014-9553-8 · 2.88 Impact Factor