Overview of Mouse Assays of Ethanol Intoxication

Crabbe, John C.; Cameron, Andy J.; Munn, Elizabeth; Bunning, Mark; Wahłsten, Douglas

doi:10.1002/0471142301.ns0926s42

Cited by 28 publications

(30 citation statements)

References 79 publications

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“…The lower end of this dose range would be expected to yield BECs in the range of many of the tested HDID-1 mice. Consistent with this notion, 39%–46% of mice in the S9 generation exhibited BECs that exceeded 100 mg% (Figure 1C), which is a value that has been shown to produce behavioral intoxication in mice (18,20). However, results with the accelerating rotarod (ARR) were more equivocal, because only mice tested second on the ARR showed signs of intoxication.…”

Section: Discussionsupporting

confidence: 72%

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A Line of Mice Selected for High Blood Ethanol Concentrations Shows Drinking in the Dark to Intoxication

Crabbe

Metten

Rhodes

et al. 2009

Biological Psychiatry

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142

218

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Background Many animal models of alcoholism have targeted aspects of excessive alcohol intake (abuse) and dependence. In the rodent, models aimed at increasing alcohol self-administration have used genetic or environmental manipulations, or their combination. Strictly genetic manipulations (e.g., comparison of inbred strains or targeted mutants, selective breeding) have not yielded rat or mouse genotypes that will regularly and voluntarily drink alcohol to the point of intoxication. Although some behavioral manipulations (e.g., scheduling or limiting access to alcohol, adding a sweetener) will induce mice or rats to drink enough alcohol to become intoxicated, these typically require significant food or water restriction or a long time to develop. We report progress toward the development of a new genetic animal model for high levels of alcohol drinking. Methods High Drinking in the Dark (HDID-1) mice have been selectively bred for high blood ethanol concentrations (BEC, ideally exceeding 100 mg%) resulting from the ingestion of a 20% alcohol solution. Results After 11 generations of selection, more than 56% of the population now exceeds this BEC after a 4-hour drinking session in which a single bottle containing 20% ethanol is available. The dose of ethanol consumed also produced quantifiable signs of intoxication. Conclusions These mice will be useful for mechanistic studies of the biological and genetic contributions to excessive drinking.

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Section: Discussionsupporting

confidence: 72%

“…The sensitivity of this task to detect intoxication is high (18), and the effective dose range across multiple inbred strains was between 1.0 and 1.4 g/kg ethanol (19). The lower end of this dose range would be expected to yield BECs in the range of many of the tested HDID-1 mice.…”

Section: Discussionmentioning

confidence: 99%

A Line of Mice Selected for High Blood Ethanol Concentrations Shows Drinking in the Dark to Intoxication

Crabbe

Metten

Rhodes

et al. 2009

Biological Psychiatry

Self Cite

142

218

View full text Add to dashboard Cite

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“…Next, rats were tested for probability discounting after injection of saline and increasing doses of EtOH (0.5 and 1.0 g/kg) in a within-subjects design. 15 minutes prior to behavioral testing, rats were injected ip with 20% EtOH prepared from a commercially-available neutral grain spirit (Everclear, Luxco, St. Louis MO; Crabbe et al, 2008) or an equivalent volume of 0.9% saline (Winchester Laboratories, Riviera Beach, FL). Rats were first treated with saline for 5 days.…”

Section: Methodsmentioning

confidence: 99%

Sex differences and hormonal modulation of ethanol-enhanced risk taking in rats

Wallin-Miller

Chesley

Castrillón

et al. 2017

Drug and Alcohol Dependence

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Background Ethanol (EtOH) intake correlates with increased risk-taking, and sex differences exist in both EtOH use and risk-taking in humans and rats. However, the interaction of sex and gonadal hormones to affect risk-taking under the influence of EtOH has not been determined. This was the focus of the current study. Methods Adult Long-Evans rats (n=18 males and females) were gonadectomized and received hormone replacement at physiologic levels or blank implants (n=7–9/group). Risk-taking was assessed with probability discounting, requiring rats to choose between a small/certain reward and a large/uncertain reward delivered with decreasing probability throughout each daily session. Before testing, rats received saline or EtOH (0.5 or 1.0 g/kg) ip. Results In males, EtOH increased preference for the large/uncertain reward lever (F2,28=10.462, p<0.05). However, there was no effect of EtOH on lever preference in females (F1,30=0.914, p>0.05). At baseline, ORCHX+T males showed a greater preference for the large/uncertain reward lever then ORCHX males (F1,14=13.805, p<0.05). In females only, EtOH decreased choice latency relative to baseline (F1,10=7.25, p<0.05). EtOH decreased loss sensitivity in both sexes, with all rats exhibiting decreased lose-shift ratios (males: F2,18=5.10, p<0.05; females F2,10=4.37, p<0.05). Conclusions These results show that EtOH, sex, and hormones interact to influence decision making. EtOH increases risk taking in males, but not in females. However, EtOH selectively decreases choice latency in females, and decreases loss sensitivity in both sexes. These findings are relevant to understanding human behavior, particularly in adolescents who experience increased hormone levels and often drink EtOH and engage in risky behavior.

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“…However, the principal limitation of two-bottle preference drinking in our opinion is that under most circumstances, even high preferring genotypes will not drink enough to become overtly intoxicated. For mice, it requires a blood ethanol concentration (BEC) of approximately 100 mg% before behavioral intoxication can be demonstrated unequivocally (Crabbe et al 2005, 2008). There are numerous methods that can be employed to elevate voluntary drinking to a degree that this threshold is surpassed.…”

Section: Beyond Alcohol Preference Drinkingmentioning

confidence: 99%

The Complexity of Alcohol Drinking: Studies in Rodent Genetic Models

2010

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Risk for alcohol dependence in humans has substantial genetic contributions. Successful rodent models generally attempt to address only selected features of the human diagnosis. Most such models target the phenotype of oral administration of alcohol solutions, usually consumption of or preference for an alcohol solution versus water. Data from rats and mice for more than 50 years have shown genetic influences on preference drinking and related phenotypes. This paper summarizes some key findings from that extensive literature. Much has been learned, including the genomic location and possible identity of several genes influencing preference drinking. We report new information from congenic lines confirming QTLs for drinking on mouse chromosomes 2 and 9. There are many strengths of the various phenotypic assays used to study drinking, but there are also some weaknesses. One major weakness, the lack of drinking excessively enough to become intoxicated, has recently been addressed with a new genetic animal model, mouse lines selectively bred for their high and intoxicating blood alcohol levels after a limited period of drinking in the circadian dark. We report here results from a second replicate of that selection and compare them with the first replicate.

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Overview of Mouse Assays of Ethanol Intoxication

Cited by 28 publications

References 79 publications

A Line of Mice Selected for High Blood Ethanol Concentrations Shows Drinking in the Dark to Intoxication

A Line of Mice Selected for High Blood Ethanol Concentrations Shows Drinking in the Dark to Intoxication

Sex differences and hormonal modulation of ethanol-enhanced risk taking in rats

The Complexity of Alcohol Drinking: Studies in Rodent Genetic Models

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