Crabbe JC, Spence SE, Brown LL, Metten P. Alcohol preference drinking in a mouse line selectively bred for high drinking in the dark. Alcohol 45: 427-440

Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University and VA Medical Center, USA.
Alcohol (Fayetteville, N.Y.) (Impact Factor: 2.01). 12/2010; 45(5):427-40. DOI: 10.1016/j.alcohol.2010.12.001
Source: PubMed


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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Available from: Pamela Metten, Oct 02, 2015
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    • "This pharmacological evidence reinforces the view that the D 3 R is necessary for ethanol consumption in mice and is consistent with rat data showing that D 3 R antagonism reduces relapse-like drinking and cue-induced ethanol-seeking behavior (Vengeliene et al, 2006). We confirmed the primary role of D 3 R in the control of ethanol-drinking behavior in a binge-like ethanol-drinking paradigm (Crabbe et al, 2011; Rhodes et al, 2005; Rhodes et al, 2007). Here, again, D 3 R À / À mice exposed to DID drank lower quantities of ethanol in comparison with their WT littermates, and D 3 R blockade by SB277011A decreased ethanol intake in WT but not in D 3 R À / À . "
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    ABSTRACT: Mesolimbic dopamine (DA) controls drug and alcohol seeking behavior, but the role of specific DA receptor subtypes is unclear. We tested the hypothesis that D3R gene deletion or the D3R pharmacological blockade inhibits ethanol preference in mice. D3R deficient mice (D3R(-/-)) and their wild type (WT) littermates, treated or not with the D3R antagonists SB277011A and U99194A, were tested in a long-term free choice ethanol-drinking (two-bottle choice) and in a binge-like ethanol drinking paradigm (drinking in the dark, DID). The selectivity of the D3R antagonists was further assessed by molecular modeling. Ethanol intake was negligible in D3R(-/-) and robust in WT both in the two-bottle choice and DID paradigms. Treatment with D3R antagonists inhibited ethanol intake in WT but was ineffective in D3R(-/-) mice. Ethanol intake increased the expression of RACK1 and BDNF in both WT and D3R(-/-); in WT there was also a robust overexpression of D3R. Thus, increased expression of D3R associated with activation of RACK1/BDNF seems to operate as a reinforcing mechanism in voluntary ethanol intake. Indeed, blockade of the BDNF pathway by the TrkB selective antagonist ANA-12 reversed chronic stable ethanol intake and strongly decreased the striatal expression of D3R. Finally, we evaluated buspirone, an approved drug for anxiety disorders endowed with D3R antagonist activity (confirmed by molecular modeling analysis), that resulted effective in inhibiting ethanol intake. Thus, DA signaling via D3R is essential for ethanol-related reward and consumption and may represent a novel therapeutic target for weaning.Neuropsychopharmacology accepted article preview online, 3 March 2014; doi:10.1038/npp.2014.51.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 03/2014; 39(8). DOI:10.1038/npp.2014.51 · 7.05 Impact Factor
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    • "Our goal was to compare baseline and post-ethanol levels of inhibitory behavior using a Go/No-Go task in two replicate lines of mice selected from a segregating stock HS/Npt (HS) to achieve high BECs during a drinking in the dark (DID) paradigm (high drinking in the dark [HDID]-1 and 2; Crabbe et al., 2009, 2011b). The DID paradigm, in which high BECs are obtained in a short time period, is commonly used to model binge drinking (Crabbe et al., 2011a). "
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    ABSTRACT: Background Alcohol consumption and behavioral inhibition share some common underlying genetic mechanisms. The current study examined whether lines of mice selected for high blood ethanol concentrations, attained by heavy drinking in the dark period (DID) of the light-dark cycle that models binge drinking, also exhibit higher levels of drug-naïve inhibition. It also examined whether the administration of ethanol would result in higher levels of disinhibition in these selected lines compared to the founder stock (HS). Methods. A Go/No-Go task was used to assess baseline inhibition and the effects of acute ethanol on disinhibition (response to a No-Go cue) in the HS line and in mice selected for high levels of DID (HDID-1 and HDID-2). Results Lines did not differ in inhibition at baseline and all lines showed increased disinhibition following moderate doses of ethanol. Ethanol decreased responding to Go cues for HDID-2 and HS lines at high doses but not HDID-1 mice. Conclusions. These data corroborate previous work showing ethanol-induced increases in behavioral disinhibition. The selection paradigm did not result in differential sensitivity to the disinhibiting effects of ethanol, but did result in differential sensitivity to the suppressant effects of ethanol on operant behavior between the two HDID lines.
    Drug and alcohol dependence 03/2014; 136(1). DOI:10.1016/j.drugalcdep.2013.12.023 · 3.42 Impact Factor
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    • "We also report water (or total fluid) consumption and body weight. Data from the occasional leaking tubes were treated as missing, as described in detail elsewhere (Crabbe et al., 2011). "
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    ABSTRACT: Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) mouse lines were bidirectionally selectively bred, respectively, to have severe or mild ethanol withdrawal handling-induced convulsions (HICs) after cessation of 3 days of ethanol vapor inhalation. Murine genotypes with severe withdrawal have been found to show low ethanol consumption, and high consumers show low withdrawal. An early drinking study with WSP and WSR mice showed modest evidence consistent with this genetic correlation, but there were several limitations to that experiment. We therefore conducted a thorough assessment of two bottle ethanol preference drinking in both replicate pairs of WSP/WSR selected lines in mice of both sexes. Greater preference drinking of WSR-2 than WSP-2 female mice confirmed the earlier report. However, in the parallel set of selected lines, the WSP-1 mice drank more than the WSR-1s. Naive mice tested for preference for sucrose, saccharin and quinine did not differ markedly for any tastant. Finally, in a test of binge-like drinking, Drinking in the Dark (DID), WSP mice drank more than WSR mice and attained significantly higher (but still modest) blood ethanol concentrations. Tests of acute withdrawal after DID showed a mild, but significant elevation in handling-induced convulsions in the WSP line. These results provide further evidence that 2-bottle ethanol preference and DID are genetically distinguishable traits.
    Alcohol (Fayetteville, N.Y.) 08/2013; 47(5):381-9. DOI:10.1016/j.alcohol.2013.05.002 · 2.01 Impact Factor
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