We are selectively breeding mice that drink sufficient EtOH to achieve high (>100 mg%) blood ethanol concentrations (BECs) during a 4 hr exposure to 20% EtOH. The HDID-1 line will be in its 20th selected generation (S20) at the time of the renewal. A second replicate (HDID-2) was started in Year 6 and will be in generation S13. The principal goal of this renewal is to continue to select these two lines. As animals are selected, we will breed additional naive mice each generation and ship them to other INIA-West investigators for their specific aims, as well as to other interested investigators. To assess pleiotropic gene effects, we will characterize the HDID lines and their HS/Npt control line for several responses to ethanol. Co-I Tamara Phillips is examining the circuitry underlying DID, using intracranial injection of test compounds to inactivate specific brain areas temporarily. Use of transmitter-specific drugs will also be considered in regions where inactivation is effective for manipulation of afferent or efferent pathways based on INIA-West targeted circuits. As relevant brain areas are identified, we will explore how intracranial injections modulate drinking microstructure. With a supplement, we obtained equipment to assess feeding and drinking microstructure simultaneously and will analyze this in the lines. We will test the hypothesis that drinking following chronic intermittent exposure to ethanol vapor is enhanced in HDID mice. The microstructure of drinking will also be explored during this post-CIE drinking.
This project addresses goals related to etiology and prediction of risk of alcohol abuse, alcoholism, and specific alcohol-related health problems. The genetic risk and protective markers that we are studying will be of utility in the future for prevention and treatment of alcoholism.
|Barkley-Levenson, Amanda M; Cunningham, Christopher L; Smitasin, Phoebe J et al. (2015) Rewarding and aversive effects of ethanol in High Drinking in the Dark selectively bred mice. Addict Biol 20:80-90|
|Crabbe, J C; Metten, P; Belknap, J K et al. (2014) Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice. Genes Brain Behav 13:236-46|
|Fritz, Brandon M; Cordero, Kristy A; Barkley-Levenson, Amanda M et al. (2014) Genetic relationship between predisposition for binge alcohol consumption and blunted sensitivity to adverse effects of alcohol in mice. Alcohol Clin Exp Res 38:1284-92|
|Barkley-Levenson, Amanda M; Crabbe, John C (2014) High drinking in the dark mice: a genetic model of drinking to intoxication. Alcohol 48:217-23|
|Thiele, Todd E; Crabbe, John C; Boehm 2nd, Stephen L (2014) "Drinking in the Dark" (DID): a simple mouse model of binge-like alcohol intake. Curr Protoc Neurosci 68:9.49.1-9.49.12|
|Hitzemann, Robert; Bottomly, Daniel; Iancu, Ovidiu et al. (2014) The genetics of gene expression in complex mouse crosses as a tool to study the molecular underpinnings of behavior traits. Mamm Genome 25:12-22|
|Bubier, Jason A; Jay, Jeremy J; Baker, Christopher L et al. (2014) Identification of a QTL in Mus musculus for alcohol preference, withdrawal, and Ap3m2 expression using integrative functional genomics and precision genetics. Genetics 197:1377-93|
|Crabbe, John C (2014) Rodent models of genetic contributions to motivation to abuse alcohol. Nebr Symp Motiv 61:5-29|
|McCulley 3rd, Walter D; Ascheid, Sonja; Crabbe, John C et al. (2013) Selective breeding for ethanol-related traits alters circadian phenotype. Alcohol 47:187-94|
|Crabbe, John C; Spence, Stephanie E; Huang, Lawrence C et al. (2013) Ethanol drinking in withdrawal seizure-prone and -resistant selected mouse lines. Alcohol 47:381-9|
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