Alcoholism, a disease of considerable morbidity, mortality and human suffering worldwide, is first and foremost characterized by excessive alcohol drinking. The """"""""Two-Hit hypothesis"""""""" that both genetic and environmental factors contribute to excessive alcohol intake is the overarching focus of our current and proposed INIA research. Microarray results from our present UO1 funding have allowed substantial inroads to be made into the understanding of both the genetic predisposition to drink and the molecular consequences of alcohol exposure. Significant candidate genes have been identified though the overlap of several of our own studies and importantly across INIA collaborations. A large searchable, open source web-base database system containing over 30 million microarray data points from our studies was created to make sharing all data within and beyond the alcoholism research field facile (publicly announced in Bergeson et al., 2005). Our current objectives are to continue to build our array database to include expression analyses of six new INIA mouse models, focus us on characterizing candidate genes that fit our """"""""two-hit hypothesis"""""""", and to use genetically altered mice and brain region specific viral mediated trans- gene and shRNA expression to test bi-directional expression (up and down regulation) effects on alcohol drinking. We will perform neurocirciutry specific microarray studies following viral-mediated gene changes in the presence and absence of alcohol drinking to better understand anatomical and molecular contributions to excessive alcohol drinking. Finally, initial studies focused on the role of miRNA and chromatin remodeling in alcohol drinking and/or consequences are proposed. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
7U01AA013475-08
Application #
7534922
Study Section
Special Emphasis Panel (ZAA1-DD (70))
Program Officer
Neuhold, Lisa
Project Start
2001-09-27
Project End
2011-08-31
Budget Start
2008-01-15
Budget End
2008-08-31
Support Year
8
Fiscal Year
2007
Total Cost
$235,015
Indirect Cost
Name
Texas Tech University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
609980727
City
Lubbock
State
TX
Country
United States
Zip Code
79430
Syapin, Peter J; Martinez, Joseph M; Curtis, David C et al. (2016) Effective Reduction in High Ethanol Drinking by Semisynthetic Tetracycline Derivatives. Alcohol Clin Exp Res 40:2482-2490
Agrawal, Rajiv G; Owen, Julie A; Levin, Patricia S et al. (2014) Bioinformatics analyses reveal age-specific neuroimmune modulation as a target for treatment of high ethanol drinking. Alcohol Clin Exp Res 38:428-37
Mulligan, Megan K; Rhodes, Justin S; Crabbe, John C et al. (2011) Molecular profiles of drinking alcohol to intoxication in C57BL/6J mice. Alcohol Clin Exp Res 35:659-70
Agrawal, R G; Hewetson, A; George, C M et al. (2011) Minocycline reduces ethanol drinking. Brain Behav Immun 25 Suppl 1:S165-9
Mulligan, M K; Ponomarev, I; Boehm 2nd, S L et al. (2008) Alcohol trait and transcriptional genomic analysis of C57BL/6 substrains. Genes Brain Behav 7:677-89
Mulligan, Megan K; Ponomarev, Igor; Hitzemann, Robert J et al. (2006) Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis. Proc Natl Acad Sci U S A 103:6368-73
Bergeson, Susan E; Kyle Warren, R; Crabbe, John C et al. (2003) Chromosomal loci influencing chronic alcohol withdrawal severity. Mamm Genome 14:454-63