Abstract

Genetic risk for development of alcoholism in humans has been shown to be related to insensitivity to the initial effects of ethanol or to the development of acute tolerance to ethanol. This project utilizes rats that have been selectively bred for insensitivity or sensitivity to the initial effects of ethanol as a model of this phenomenon in humans. The project seeks to identify the genes responsible for this response in rats, to compare these results with similar studies in other rat selection studies and in mice to predict which genes may be responsible for the genetic risk factors in humans. The research utilizes methods of Quantitative Trait Loci (QTL) determination to locate these genes within the genome of the rat. Other breeding (development of congenic strains) and molecular biological methods are then used to focus on a narrower region of the genome in which these genes reside. This will allow the identification of the genes and show that they are responsible for a portion of the response to ethanol in the whole animal. This information is then applied to studies in humans to predict where genes will be found that influence the risk of development of alcoholism in humans. Development of prevention or treatment strategies will then be possible.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA011464-08
Application #
7065208
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Neuhold, Lisa
Project Start
1998-09-18
Project End
2008-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
8
Fiscal Year
2006
Total Cost
$627,830
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Pharmacology
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Deng, Xin-sheng; Deitrich, Richard A (2008) Putative role of brain acetaldehyde in ethanol addiction. Curr Drug Abuse Rev 1:3-8
Deitrich, Richard A; Petersen, Dennis; Vasiliou, Vasilis (2007) Removal of acetaldehyde from the body. Novartis Found Symp 285:23-40;discussion 40-51, 198-9
Deng, Xin-Sheng; Deitrich, Richard A (2007) Ethanol metabolism and effects: nitric oxide and its interaction. Curr Clin Pharmacol 2:145-53
Radcliffe, Richard A; Bludeau, Pequita; Deng, Xin-Sheng et al. (2007) Short-term selection for acute ethanol tolerance and sensitization from an F2 population derived from the high and low alcohol-sensitive selectively bred rat lines. Alcohol 41:557-66
Radcliffe, Richard A; Bludeau, Pequita; Asperi, William et al. (2006) Confirmation of quantitative trait loci for ethanol sensitivity and neurotensin receptor density in crosses derived from the inbred high and low alcohol sensitive selectively bred rat lines. Psychopharmacology (Berl) 188:343-54
Radcliffe, Richard A; Erwin, V Gene; Draski, Laura et al. (2004) Quantitative trait loci mapping for ethanol sensitivity and neurotensin receptor density in an F2 intercross derived from inbred high and low alcohol sensitivity selectively bred rat lines. Alcohol Clin Exp Res 28:1796-804
Deitrich, Richard A (2004) Acetaldehyde: deja vu du jour. J Stud Alcohol 65:557-72
Freund, Ronald K; Gerhardt, Greg A; Marshall, Kriste E et al. (2003) Differences in norepinephrine clearance in cerebellar slices from low-alcohol-sensitive and high-alcohol-sensitive rats. Alcohol 30:9-18
McBride, William J; Li, Ting-Kai; Deitrich, Richard A et al. (2002) Involvement of acetaldehyde in alcohol addiction. Alcohol Clin Exp Res 26:114-9
Dahchour, A; Hoffman, A; Deitrich, R et al. (2000) Effects of ethanol on extracellular amino acid levels in high-and low-alcohol sensitive rats: a microdialysis study. Alcohol Alcohol 35:548-53

Showing the most recent 10 out of 11 publications