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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA013519-12
Application #
8327807
Study Section
Special Emphasis Panel (ZAA1-DD (50))
Program Officer
Parsian, Abbas
Project Start
2001-09-27
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
12
Fiscal Year
2012
Total Cost
$441,074
Indirect Cost
$91,015
Name
Oregon Health and Science University
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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Metten, Pamela; Schlumbohm, Jason P; Huang, Lawrence C et al. (2018) An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice. Alcohol 68:19-35
Iancu, Ovidiu Dan; Colville, Alex M; Wilmot, Beth et al. (2018) Gender-Specific Effects of Selection for Drinking in the Dark on the Network Roles of Coding and Noncoding RNAs. Alcohol Clin Exp Res :
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Crabbe, John C; Ozburn, Angela R; Metten, Pamela et al. (2017) High Drinking in the Dark (HDID) mice are sensitive to the effects of some clinically relevant drugs to reduce binge-like drinking. Pharmacol Biochem Behav 160:55-62
Colville, A M; Iancu, O D; Oberbeck, D L et al. (2017) Effects of selection for ethanol preference on gene expression in the nucleus accumbens of HS-CC mice. Genes Brain Behav 16:462-471
Hitzemann, Robert; Oberbeck, Denesa; Iancu, Ovidiu et al. (2017) Alignment of the transcriptome with individual variation in animals selectively bred for High Drinking-In-the-Dark (HDID). Alcohol 60:115-120

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