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

Portland Alcohol Research Center, Portland, Oregon, USA.
Biological psychiatry (Impact Factor: 10.26). 04/2009; 65(8):662-70. DOI: 10.1016/j.biopsych.2008.11.002
Source: PubMed


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.
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.
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.
These mice will be useful for mechanistic studies of the biological and genetic contributions to excessive drinking.

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Available from: Pamela Metten
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    • "The DID phenotype is genetically influenced, since studies with inbred mouse strains have indicated similar DID alcohol consumption within strains and different levels of DID alcohol consumption across strains (Rhodes et al. 2007). Furthermore, successful selective breeding for high blood ethanol levels achieved during DID has been accomplished, leading to replicate selected HDID1 and HDID2 mouse lines (Crabbe et al. 2009). In these animals, the blood ethanol concentration correlates with the amount of alcohol consumed in the DID protocol. "
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    • "different circa - dian phenotypes . In high and low alcohol - preferring mice ( HAP - 1 and LAP - 1 , respectively ) , HAP - 1 mice have shorter circadian periods in constant darkness ( DD ) than LAP - 1 mice ( Hofstetter , Grahame , & Mayeda , 2003 ) . Other high drinking mouse lines , such as the High Drinking in the Dark ( HDID - 1 and Ϫ2 ) , ( Crabbe et al . , 2009 ; Crabbe , Spence , Brown , & Metten , 2011 ; Rhodes , Best , Belknap , Finn , & Crabbe , 2005 ) , display shorter free - running periods and less coherent activity rhythms in LL relative to the genetically heterogeneous progenitor line ( Hs / Npt ) controls ( Mc - This document is copyrighted by the American Psychological Association o"
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    • "The observation that the M-AFT and AFT capacity of HDID-1 was similar or even lower than HS/Npt mice may also not be all that surprising given their selection phenotype. The selection phenotype for HDID mice consists of 2 presentations of alcohol: one 2-hour DID access period on day 1 and a 4-hour access period on day 2 (Crabbe et al., 2009). Mice were selected this way because EtOH DID intake on day 2 strongly correlated with intake on subsequent days in studies with C57BL/6J mice, the inbred mouse strain with which the DID paradigm was developed (Rhodes et al., 2005). "
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