OVERVIEW Persistent changes in gene expression may mediate many effects of alcohol including reward learning, tolerance and dependence, suggesting that agents effective in changing alcohol-induced gene expression could be considered as therapeutic agents. Drugs targeting gene expression through inhibition of enzymes that regulate chromatin structure (epigenetic drugs) have been widely used in cancer research and recently emerged as potential therapeutics for neurodegenerative disorders and drug addiction. The main goals of this project are: 1) to identify epigenetic drugs that affect alcohol reward through testing their effects on alcohol consumption and conditioned place preference (CPP) and 2) to investigate the effects of selected epigenetic drugs on gene expression and cellular physiology in the reward pathway including the ventral tegmental area (VTA) and the nucleus accumbens (NA). The overall hypothesis is that some epigenetic drugs will reduce the rewarding properties of alcohol through changes in gene expression and cellular physiology in the reward pathway. Integration of electrophysiological and gene expression data will elucidate the drug's mechanisms of action and identify novel targets for drug development. This research will provide initial mechanistic evidence for the therapeutic potential of epigenetic drugs in treating alcohol addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Program Projects (P01)
Project #
1P01AA020683-01
Application #
8201635
Study Section
Special Emphasis Panel (ZAA1-GG (21))
Project Start
2012-05-04
Project End
2017-04-30
Budget Start
2012-05-04
Budget End
2013-04-30
Support Year
1
Fiscal Year
2012
Total Cost
$145,062
Indirect Cost
$32,562
Name
University of Texas Austin
Department
Type
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
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Kirson, Dean; Cornelison, Garrett L; Philpo, Ashley E et al. (2013) Physiological concentrations of zinc reduce taurine-activated GlyR responses to drugs of abuse. Neuropharmacology 75:286-94