Selective breeding for high low alcohol preference in mice

Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
Behavior Genetics (Impact Factor: 3.21). 02/1999; 29(1):47-57. DOI: 10.1023/A:1021489922751
Source: PubMed


High and low alcohol preference (HAP and LAP, respectively) mice were created by 10 generations of bidirectional selection for differences in two-bottle choice alcohol consumption. The progenitors used for selection were HS/lbg mice, which are a genetically defined, outbred stock. During selection, mice had 24-h, daily access to 10% alcohol (v/v) and water ad libitum for 30 days and were selected based on the alcohol (g/kg) consumed per day over the entire period. Food was available ad libitum. At S10, line means for alcohol consumption differed greatly, with consumption of over 12 g/kg per day in the HAP mice and less than 2 g/kg per day in the LAP mice. Realized heritability for bidirectional selection was approximately 0.2. Female mice consumed more alcohol than male mice. There were no differences between lines in alcohol elimination rate, nor were there line differences in intake of salt or quinine solutions. However, consumption of saccharin solutions was greater in HAP mice than LAP mice, consistent with previous findings of a genetic correlation between sweet preference and alcohol drinking. Because the mouse genome is relatively well characterized, these selected lines should prove a useful tool for assessment of the genetic basis of, and phenotypes that correlate with, alcohol drinking.

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    • "With repeated cycles of continuous - access 2 - bottle choice drinking , HAP mice typically increase their ethanol intake and preference over days ( Grahame et al . , 1999 ; Matson & Grahame , 2011 ; Oberlin et al . , 2011 ) , and this was generally the case in the current study . Given our previous findings ( Fritz et al . , 2013 ) , we hypothesized that a prior history of alcohol consumption may enhance the already substantial rapid AFT capacity of HAP2 mice . It was found that an ethanol consumption hi"
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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 · 2.01 Impact Factor
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    • "Because of the difficulty in directly examining genetic effects in humans, several lines of mice have been developed to help understand the genetic components of alcohol consumption . Such lines include the high-and low-alcohol preferring mice (HAP/LAP; Grahame et al., 1999) and the high-and low-drinking short-term-selected mice (STDRHI/ STDRLO; Phillips et al., 2005). In addition to consumption of alcohol, a number of mice have been selected on other alcohol-related traits, such as sensitivity to alcohol-induced stimulation (FAST/SLOW mice; Crabbe et al., 1987), sensitivity to alcohol-induced loss of righting reflex (short/long sleep mice [SS/LS]; Fuller, 1980), and severity of alcohol withdrawal (after chronic alcohol: Withdrawal Seizure Resistant/Prone mice [WSR/WSP], Kosobud and Crabbe, 1986; after acute alcohol: high-and low-alcohol withdrawal mice [first replicate: HAW-1/LAW-1], Metten et al., 1998a). "
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    ABSTRACT: Background: Mice selectively bred for high or low withdrawal to acute alcohol differ on a number of traits, including consumption of alcohol, conditioned place preference for alcohol, and sensitivity to alcohol-induced locomotor activity. One trait that has not been examined in these mice is behavioral inhibition. Methods: High and low alcohol withdrawal mice (second replicate: high and low acute alcohol withdrawal [HAW-2/LAW-2]) were trained and tested in a Go/No-go task. Mice were administered 0.0, 0.5, 1.0, and 1.5 g/kg ethanol (EtOH) on 3 occasions according to an incomplete Latin Square. A separate cohort of C57BL/6J (B6) and DBA/2J (D2) mice (the progenitor strains for HAW-2/LAW-2 mice) underwent the same protocol, using the same EtOH doses. Results: HAW-2 and LAW-2 mice did not differ in behavioral inhibition at baseline, although LAW-2 mice did have higher overall levels of responding in the task. EtOH did not alter behavioral inhibition in these mice. However, it did decrease responses to the Go cue, and this effect was greater in HAW-2 mice than in LAW-2 mice. D2 mice had lower behavioral inhibition than B6 mice at baseline, and EtOH slightly decreased behavioral inhibition in both strains. Conclusions: The findings with D2 and B6 mice generally fit with the existing literature. However, the lack of a difference in behavioral inhibition between HAW-2 and LAW-2 mice was unexpected, as well as the absence of any effect of these doses of EtOH on behavioral inhibition in these mice. Nonetheless, the findings do suggest that selectively breeding for high or low withdrawal to acute alcohol can lead to differences in operant behavior in the Go/No-go task.
    Alcoholism Clinical and Experimental Research 04/2013; 37(9). DOI:10.1111/acer.12134 · 3.21 Impact Factor
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    • "Lines of rodents have been selectively bred for high (HAFT) and low (LAFT) AFT (Erwin & Deitrich 1996), although the relationship between AFT and alcohol consumption in these lines is ill-defined as neither consumes significant amounts of alcohol (Erwin et al. 2000). Investigating AFT in lines selected for alcohol preference, such as the high (HAP) and low (LAP) alcohol-preferring selected mouse lines (Grahame et al. 1999), may therefore offer a more complete picture of the relationship between the two phenotypes. Although no difference in AFT development between lines was observed in the first replicate of HAP and LAP lines (Grahame et al. 2000), AFT has yet to be investigated in the second and third replicate lines. "
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    ABSTRACT: Propensity to develop acute functional (or within session) tolerance to alcohol (ethanol) may influence the amount of alcohol consumed, with higher drinking associated with greater acute functional tolerance (AFT). The goal of this study was to assess this potential correlated response between alcohol preference and AFT in second and third replicate lines of mice selectively bred for high (HAP2 and HAP3) and low (LAP2 and LAP3) alcohol preference drinking. Male and female mice were tested for development of AFT on a static dowel task, which requires that animals maintain balance on a wooden dowel in order to prevent falling. On test day, each mouse received one (1.75 g/kg; Experiment 1) or two (1.75 and 2.0 g/kg; Experiment 2) injections of ethanol; an initial administration before being placed on the dowel and in Experiment 2, an additional administration after the first regain of balance on the dowel. Blood samples were taken immediately after loss of balance [when blood ethanol concentrations (BECs) were rising] and at recovery (during falling BECs) in Experiment 1, and after first and second recovery in Experiment 2. It was found that HAP mice fell from the dowel significantly earlier and at lower BECs than LAP mice following the initial injection of ethanol and were therefore more sensitive to its early effects. Furthermore, Experiment 1 detected significantly greater AFT development (BECfalling - BECrising) in HAP mice when compared with LAP mice, which occurred within ∼30 min, supporting our hypothesis. However, AFT was not different between lines in Experiment 2, indicating that ∼30-60 min following alcohol administration, AFT development was similar in both lines. These data show that high alcohol drinking genetically associates with both high initial sensitivity and very early tolerance to the ataxic effects of ethanol.
    Genes Brain and Behavior 07/2012; 12(1). DOI:10.1111/j.1601-183X.2012.00830.x · 3.66 Impact Factor
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