Abstract

This is a supplemental application to take advantage of a highly significant Quantitative Trait Locus (QTL) on chromosome 1 for high dose ethanol sensitivity that we have discovered in the Inbred Alcohol non- Tolerant (IANT) and the inbred Alcohol Tolerant (IAT rats) in spite of the fact that these animals were selectively bred for low dose effects. This QTL is in the same general location as one for this phenotype in the inbred High Alcohol Sensitive (IHAS) and inbred Low Alcohol Sensitive (ILAS) rats, but is much more significant and has a much higher heritability. We will take advantage of this unique opportunity to add to our knowledge of ethanol sensitivity by construction of congenic strains for the QTL, narrowing the region of the QTL and comparing the results to the same region in the I HAS and I LAS rats. We are also constructing congenic strains from the I HAS and I LAS rats on chromosomes 2 and 5. The QTL on chromosome 1 in the IHAS and ILAS rats is much smaller than in the IANT and IAT rats. These studies are important since among the risk factors for alcoholism in humans is a low initial sensitivity and/or rapid development of tolerance to ethanol. We have two animal models of this behavior, the rats selectively bred for high dose sensitivity (the IHAS and ILAS) and animals bred for low dose sensitivity (the IAT and IANT) ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
3R01AA011464-07S1
Application #
6966939
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Neuhold, Lisa
Project Start
1998-09-18
Project End
2008-05-31
Budget Start
2005-08-10
Budget End
2006-05-31
Support Year
7
Fiscal Year
2005
Total Cost
$228,981
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