The long-range objectives of this project are to better understand the complex neuronal alterations that occur as a result of alcohol exposure and contribute to high alcohol drinking and relapse behaviors in genetically vulnerable subjects. Compelling evidence implicates the ventral tegmental area (VTA) and nucleus accumbens (ACB) in mediating the reinforcing effects of ethanol (EtOH) and alcohol drinking. The overall hypothesis to be tested is that the mesolimbic system of genetically vulnerable subjects is sensitive to EtOH and undergoes molecular neurobiological changes that contribute to high alcohol drinking and relapse behavior. The overall hypothesis will be tested in the selectively bred alcohol-preferring (P) and high-alcohol-drinking (HAD) lines of rats, using a micro-punch technique to isolate the VTA and the ACB-shell (sh). State-of-the-art microarray procedures will be used to determine (a) acute EtOH-responsive genes in the VTA and ACB-sh, and (b) changes in gene expression that result from chronic alcohol self-administration and persist in the absence of alcohol. Two of the aims will determine genes that are differentially responsive to EtOH in lines of rats that respond differently to EtOH and have different alcohol drinking characteristics, i.e., P and HAD rats and their low-alcohol-consuming counterparts, alcohol-non-preferring (NP) and low-alcohol-drinking (LAD) rats. Two other aims will use operant techniques to determine the effects of EtOH self-administration by P and HAD rats on gene expression in the VTA and ACB-sh, and whether some of the changes in gene expression produced by chronic EtOH self-administration persist in the absence of EtOH. The results of these latter two aims will identify genes that have altered expression due to chronic EtOH self-administration and may contribute to relapse. Overall, the findings from this project will provide valuable information on EtOH-induced molecular neurobiological changes that occur within limbic regions of vulnerable individuals and may contribute to high alcohol drinking behavior and alcohol relapse. Such information would be important for determining potentially therapeutic pharmacological treatments for reducing alcohol drinking and relapse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
5P60AA007611-24
Application #
8208635
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2010-12-01
Budget End
2011-11-30
Support Year
24
Fiscal Year
2011
Total Cost
$208,330
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Ding, Zheng-Ming; Ingraham, Cynthia M; Hauser, Sheketha R et al. (2017) Reduced Levels of mGlu2 Receptors within the Prelimbic Cortex Are Not Associated with Elevated Glutamate Transmission or High Alcohol Drinking. Alcohol Clin Exp Res 41:1896-1906
Hendershot, Christian S; Wardell, Jeffrey D; McPhee, Matthew D et al. (2017) A prospective study of genetic factors, human laboratory phenotypes, and heavy drinking in late adolescence. Addict Biol 22:1343-1354
Czachowski, Cristine L; Froehlich, Janice C; DeLory, Michael (2017) The Effects of Long-Term Varenicline Administration on Ethanol and Sucrose Seeking and Self-Administration in Male P Rats. Alcohol Clin Exp Res :
Linsenbardt, David N; Smoker, Michael P; Janetsian-Fritz, Sarine S et al. (2017) Impulsivity in rodents with a genetic predisposition for excessive alcohol consumption is associated with a lack of a prospective strategy. Cogn Affect Behav Neurosci 17:235-251
Froehlich, Janice C; Fischer, Stephen M; Nicholson, Emily R et al. (2017) A Combination of Naltrexone + Varenicline Retards the Expression of a Genetic Predisposition Toward High Alcohol Drinking. Alcohol Clin Exp Res 41:644-652
Weera, Marcus M; Fields, Molly A; Tapp, Danielle N et al. (2017) Effects of Nicotine on Alcohol Drinking in Female Mice Selectively Bred for High or Low Alcohol Preference. Alcohol Clin Exp Res :
Froehlich, Janice C; Nicholson, Emily R; Dilley, Julian E et al. (2017) Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol-Preferring (P) Rats. Alcohol Clin Exp Res 41:1510-1517
Liang, Tiebing; Chalasani, Naga P; Williams, Kent Edward et al. (2017) Differential Expression of miRNAs in Nontumor Liver Tissue of Patients With Hepatocellular Cancer Caused by Nonalcoholic Steatohepatitis Cirrhosis. Clin Gastroenterol Hepatol 15:465-467
Gowin, Joshua L; Sloan, Matthew E; Stangl, Bethany L et al. (2017) Vulnerability for Alcohol Use Disorder and Rate of Alcohol Consumption. Am J Psychiatry 174:1094-1101
King, Andrea C; Hasin, Deborah; O'Connor, Sean J et al. (2016) A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder. Biol Psychiatry 79:489-98

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