This project continue research started with funding by an ongoing Program Project Grant. The central research goal of our current program project was to determine the extent to which there were common genetic determinants of different measures of neuroadaptation to ethanol. Genetic mapping techniques brought to fruition early during the course of the current grant allowed provisional identification of the map location of individual genes (Quantitative Trait Loci, or QTLs) affecting behavioral and pharmacological responses to ethanol. In particular, potential QTLs have been identified that are associated with multiple measures of ethanol tolerance and dependence. Our major theme to be carried forward into the Center from the initial program period is a focus on mapping and verification of provisional QTLs relevant for neuroadaptation to ethanol, and development of new genetic animal models (e.g., congenic strains) for studying the effects of verified QTLs. The ultimate goal of these studies is to identify the specific relevant genes and their functional roles. The second major theme is the use of genetic animal models to explore the neuropharmacological and neuroendocrine mechanisms underlying ethanol responses.
The aims of Component #3 are related to both overall Center themes. They develop new congenic strains for studying genes affecting hypothermia and ataxia traits during tolerance and dependence, as well as other alcohol responses studies in other Center projects. They also continue to explore mechanisms through which neuroadaptation to ethanol's thermal and metabolic effects develops. The general goals of the proposed experiments are to: (1) subject selected potential thermoregulatory and ataxia QTLs to confirmation testing in populations of B6D2F2 mice; (2) develop congenic strains based on genotypes with extremes intolerance development to ethanol hypothermia and/or ataxia; (3) extend studies of the BXD RI strains to analyze the thermoregulatory, disruptive and energetic changes that occur during the development of thermal tolerance, using measures of behavioral thermoregulation and metabolism; (4) similarly, extend studies of the BXD RI strains to thermoregulatory and metabolic alterations that are seen during withdrawal; and (5) perform QTL analyzes of the latter two groups of responses.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
5P50AA010760-03
Application #
6267130
Study Section
Project Start
1997-12-01
Project End
1998-11-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Iancu, Ovidiu D; Colville, Alexander; Walter, Nicole A R et al. (2018) On the relationships in rhesus macaques between chronic ethanol consumption and the brain transcriptome. Addict Biol 23:196-205
Purohit, Kush; Parekh, Puja K; Kern, Joseph et al. (2018) Pharmacogenetic Manipulation of the Nucleus Accumbens Alters Binge-Like Alcohol Drinking in Mice. Alcohol Clin Exp Res 42:879-888
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 :
Aoun, E G; Jimenez, V A; Vendruscolo, L F et al. (2018) A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans. Mol Psychiatry 23:1466-1473
Buck, Kari J; Chen, Gang; Kozell, Laura B (2017) Limbic circuitry activation in ethanol withdrawal is regulated by a chromosome 1 locus. Alcohol 58:153-160
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
Chesler, Elissa J; Gatti, Daniel M; Morgan, Andrew P et al. (2016) Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection. G3 (Bethesda) 6:3893-3902
Crabbe, John C; Schlumbohm, Jason P; Hack, Wyatt et al. (2016) Fear conditioning in mouse lines genetically selected for binge-like ethanol drinking. Alcohol 52:25-32

Showing the most recent 10 out of 162 publications