The long-range goals of this 5-year proposal are to understand, in the CNS of genetically vulnerable subjects, the complex neuronal alterations that occur as a result of alcohol exposure, which promote high alcohol drinking behavior and relapse. The overall hypothesis is that, in individuals with a genetic predis-position for high alcohol drinking behavior, certain CNS neuronal circuits are susceptible to alterations by alcohol and, as a result, high alcohol drinking is initiated and maintained, and alcohol relapse drinking is promoted. The goals of the present proposal are to determine the long-term changes in gene and protein expression produced by voluntary alcohol drinking that may be associated with high alcohol drinking and relapse. Inbred adult male alcohol preferring (iP), high-alcohol-drinking (iliAD), alcohol-non-preferring (iNP) and low-alcohol-drinking (iLAD) rats will be used for these studies. The microchip expression array will be used to examine changes in gene expression, and 2-dimensional gel electrophoresis procedures will be used to examine changes in protein expression. The first 2 specific aims will compare innate differences between iP and iNP rats and between replicate iliAD and iLAD rats, and determine the effects of voluntary alcohol drinking by iP and iliAD rats on changes in gene and protein expression in the nucleus accumbens, prefrontal cortex and posterior hippocampus. The second 2 specific aims will examine the effects of operant oral alcohol self-administration, extinction training and reinstatement on gene and protein expression in these limbic regions of the iP and iliAD rats. This research component integrates well with the Center's theme of studying genetic determinants of alcohol ingestion. The proposed project interacts directly with the following cores: Administrative, Animal Production, Genomics and Molecular Biology, and Proteomics. This rat genetic component complements the 2 research components dealing with Human Genetics, and scientifically interacts with the Mouse Selective Breeding and Genetics Component. The results of this project will provide valuable information on mechanisms underlying alcohol addiction, which could lead to the development of pharmacotherapies for the treatment of alcoholism and alcohol abuse.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Comprehensive Center (P60)
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Special Emphasis Panel (ZAA1)
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Indiana University-Purdue University at Indianapolis
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Chumin, Evgeny J; Goñi, Joaquín; Halcomb, Meredith E et al. (2018) Differences in White Matter Microstructure and Connectivity in Nontreatment-Seeking Individuals with Alcohol Use Disorder. Alcohol Clin Exp Res 42:889-896
Eiler 2nd, William J A; Dzemidzic, Mario; Soeurt, Christina M et al. (2018) Family history of alcoholism and the human brain response to oral sucrose. Neuroimage Clin 17:1036-1046
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 :

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