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-alcoholdrinking (HAD) lines of rats, using a micro-punch technique to isolate the VTA and the ACB-shell (sh). Stateof- 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-alcoholdrinking (LAD) rats. Two other aims will use operant techniques to determine the effects of EtOH selfadministration 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 selfadministration 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.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Comprehensive Center (P60)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Indiana University-Purdue University at Indianapolis
United States
Zip Code
Weafer, Jessica; Ross, Thomas J; O'Connor, Sean et al. (2018) Striatal activity correlates with stimulant-like effects of alcohol in healthy volunteers. Neuropsychopharmacology 43:2532-2538
Weera, Marcus M; Fields, Molly A; Tapp, Danielle N et al. (2018) Effects of Nicotine on Alcohol Drinking in Female Mice Selectively Bred for High or Low Alcohol Preference. Alcohol Clin Exp Res 42:432-443
Gerke, Steven P; Agley, Jon D; Wilson, Cynthia et al. (2018) An Initial Assessment of the Utility of Validated Alcohol and Drug Screening Tools in Predicting 30-Day Readmission to Adult General Medicine Wards. Am J Med Qual 33:397-404
Bujarski, Spencer; Jentsch, J David; Roche, Daniel J O et al. (2018) Differences in the subjective and motivational properties of alcohol across alcohol use severity: application of a novel translational human laboratory paradigm. Neuropsychopharmacology 43:1891-1899
Plawecki, Martin Henry; White, Kurt; Kosobud, Ann E K et al. (2018) Sex Differences in Motivation to Self-Administer Alcohol After 2 Weeks of Abstinence in Young-Adult Heavy Drinkers. Alcohol Clin Exp Res 42:1897-1908
Plawecki, Martin H; Windisch, Kyle A; Wetherill, Leah et al. (2018) Alcohol affects the P3 component of an adaptive stop signal task ERP. Alcohol 70:1-10
Houck, Christa A; Grahame, Nicholas J (2018) Acute drug effects on habitual and non-habitual responding in crossed high alcohol preferring mice. Psychopharmacology (Berl) 235:2167-2175
Kareken, David A (2018) Missing motoric manipulations: rethinking the imaging of the ventral striatum and dopamine in human reward. Brain Imaging Behav :
Czachowski, Cristine L; Froehlich, Janice C; DeLory, Michael (2018) The Effects of Long-Term Varenicline Administration on Ethanol and Sucrose Seeking and Self-Administration in Male P Rats. Alcohol Clin Exp Res 42:453-460
Spence, John Paul; Reiter, Jill L; Qiu, Bin et al. (2018) Estrogen-Dependent Upregulation of Adcyap1r1 Expression in Nucleus Accumbens Is Associated With Genetic Predisposition of Sex-Specific QTL for Alcohol Consumption on Rat Chromosome 4. Front Genet 9:513

Showing the most recent 10 out of 308 publications