Functional magnetic resonance imaging (fMRI) has only recently begun to identify specific brain regions where responses to stimuli associated with dnnking ("alcohol cues") vary as a function of a family history of alcoholism (Kareken et al., 2010a;Tapert et al., 2003). The long-term goal of our research is to determine how alcoholism risk factors alter the brain's reward system function. The objective of this application is to determine how genetic, behavioral, and personality trait risks alter the brain's processing of cues that have been classically conditioned to predict imminent intoxication in the expenmental setting. Our rationale is that, by carefully controlling learning and contingencies in the laboratory, we can better measure brain responses to alcohol predictive cues, and do so with cues devoid of the influence from prior idiosyncratic alcohol experiences. The central hypothesis of these studies is that brain responses to cued alcohol intoxication will differ as a function of both genetic and behavioral risk factors. By identifying the brain systems affected by family history, behavioral disorders, and specific genes, we will gain a more complete understanding of the nsk pathways and associated neural vulnerabilities that help lead to alcoholism. Using fMRI, we will test three specific aims: 1) Test whether a family history of alcoholism alters brain responses to novel cues experimentally paired with the ascending limb of the blood alcohol curve. 2) Test whether brain responses to experimentally conditioned cues are modified by the presence of high externalizing behaviors. 3) Test whether GABRA2 variation affects local brain responses to cues experimentally conditioned to intoxication.

Public Health Relevance

Our proposed research will identify how alcoholism risk factors are reflected by brain responses that encode the anticipation of impending alcohol intoxication and how the human brain learns about stimuli (sensations) that predict imminent intoxication? stimuli that can eventually increase alcohol cravings and impel individuals to seek alcohol.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
2P60AA007611-26
Application #
8400536
Study Section
Special Emphasis Panel (ZAA1-GG (50))
Project Start
Project End
Budget Start
2012-12-25
Budget End
2013-11-30
Support Year
26
Fiscal Year
2013
Total Cost
$322,729
Indirect Cost
$105,190
Name
Indiana University-Purdue University at Indianapolis
Department
Type
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
O'Tousa, David S; Warnock, Kaitlin T; Matson, Liana M et al. (2015) Triple monoamine uptake inhibitors demonstrate a pharmacologic association between excessive drinking and impulsivity in high-alcohol-preferring (HAP) mice. Addict Biol 20:236-47
Oberlin, Brandon G; Dzemidzic, Mario; Tran, Stella M et al. (2015) Beer self-administration provokes lateralized nucleus accumbens dopamine release in male heavy drinkers. Psychopharmacology (Berl) 232:861-70
Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A (2015) Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement. Alcohol 49:149-63
Guillot, Casey R; Fanning, Jennifer R; Liang, Tiebing et al. (2015) COMT Associations with Disordered Gambling and Drinking Measures. J Gambl Stud 31:513-24
Azarov, Alexey V; Woodward, Donald J (2014) Early ethanol and water consumption: accumulating experience differentially regulates drinking pattern and bout parameters in male alcohol preferring (P) vs. Wistar and Sprague Dawley rats. Physiol Behav 123:20-32
Montane Jaime, Lazara Karelia; Shafe, Samuel; Liang, Tiebing et al. (2014) Subjective response to alcohol and ADH polymorphisms in a select sample of young adult male East Indians and Africans in Trinidad and Tobago. J Stud Alcohol Drugs 75:827-38
Beckwith, S Wesley; Czachowski, Cristine L (2014) Increased delay discounting tracks with a high ethanol-seeking phenotype and subsequent ethanol seeking but not consumption. Alcohol Clin Exp Res 38:2607-14
Kasten, Chelsea R; Boehm 2nd, Stephen L (2014) Intra-nucleus accumbens shell injections of R(+)- and S(-)-baclofen bidirectionally alter binge-like ethanol, but not saccharin, intake in C57Bl/6J mice. Behav Brain Res 272:238-47
Toalston, Jamie E; Deehan Jr, Gerald A; Hauser, Sheketha R et al. (2014) Reinforcing properties and neurochemical response of ethanol within the posterior ventral tegmental area are enhanced in adulthood by periadolescent ethanol consumption. J Pharmacol Exp Ther 351:317-26
Hoffman, P L; Saba, L M; Flink, S et al. (2014) Genetics of gene expression characterizes response to selective breeding for alcohol preference. Genes Brain Behav 13:743-57

Showing the most recent 10 out of 124 publications