The themes of the Indiana Alcohol Research Center (IARC) renewal "Genetics of Alcoholism and Responses to Alcohol" are to identify correlates between risk factors (e.g., a positive family history of alcohol use disorders (AUD), externalizing behaviors (including different forms of impulsive behavior), patterns of binge drinking, and GABRA2 alleles) and: 1) measures of craving alcohol (assessed by operant work for alcohol using paradigms we have developed for both animals and humans), and 2) brain responses to novel cues conditioned to alcohol intoxication.
Our aims will advance NIAAA's goal of identifying the physiological traits of alcohol risk endophenotypes. We will extend our knowledge of the basis for alcohol preference in rats by sequencing the genomes of P/NP and HAD/LAD rats and defining the sequences resulting from selective breeding. With these complementary, parallel investigations, our Center fulfills a critical need to integrate human and animal studies of how risk genes affect responses and endophenotypes related to AUDs. The rationale for continuing our Center is that: 1) by working in close association across scientific disciplines spanning behavioral neuroscience, neuroanatomy, molecular biology, genetics, genomics, biochemistry, neurobiology, and bioinformatics, our investigators can achieve insights that are not possible when working in isolation, 2) the Center has made unique contributions to alcoholism research and dissemination of resources around the world, 3) it combines human and animal studies examining overlapping risk factors for AUDs, and 4) it provides an unparalleled multi-disciplinary training environment for students, fellows, and young faculty. The expected outcome of our combined work, in toto, is a far greater understanding of the relationship between genetic and behavioral risk factors for AUDs, as well as the mechanisms through which these genetic factors act. The positive impact of such knowledge will be the ability to better target future prevention and treatment strategies, and to advance our understanding of factors influencing how the human brain governs the approach toward, consumption of, response to, and eventually dependence upon alcohol intoxication. These outcomes will be achieved through the activities and interactions of Administrative, Animal Production, and Genomics and Bioinformatics Cores, a Pilot Projects and Translational Research and Science Education Component, and five research Components: two carrying out cutting edge translational human research with alcohol infusion technology invented by IARC researchers, and three using animal models created and characterized by IARC investigators.

Public Health Relevance

This work will provide novel information about the ways several risk factors for alcohol use disorders, such as family history of alcoholism, personality traits, and certain specific genes, modify responses to alcohol and increase the chances of developing problems with drinking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
2P60AA007611-26
Application #
8393883
Study Section
Special Emphasis Panel (ZAA1-GG (50))
Program Officer
Murray, Gary
Project Start
1989-12-01
Project End
2017-11-30
Budget Start
2012-12-25
Budget End
2013-11-30
Support Year
26
Fiscal Year
2013
Total Cost
$1,797,423
Indirect Cost
$634,567
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Wardell, Jeffrey D; Ramchandani, Vijay A; Hendershot, Christian S (2016) Drinking Motives Predict Subjective Effects of Alcohol and Alcohol Wanting and Liking During Laboratory Alcohol Administration: A Mediated Pathway Analysis. Alcohol Clin Exp Res 40:2190-2198
McClintick, Jeanette N; McBride, William J; Bell, Richard L et al. (2016) Gene Expression Changes in Glutamate and GABA-A Receptors, Neuropeptides, Ion Channels, and Cholesterol Synthesis in the Periaqueductal Gray Following Binge-Like Alcohol Drinking by Adolescent Alcohol-Preferring (P) Rats. Alcohol Clin Exp Res 40:955-68
Yoder, Karmen K; Albrecht, Daniel S; Dzemidzic, Mario et al. (2016) Differences in IV alcohol-induced dopamine release in the ventral striatum of social drinkers and nontreatment-seeking alcoholics. Drug Alcohol Depend 160:163-9
Bell, R L; Hauser, S; Rodd, Z A et al. (2016) A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction. Int Rev Neurobiol 126:179-261
Sari, Youssef; Toalston, Jamie E; Rao, P S S et al. (2016) Effects of ceftriaxone on ethanol, nicotine or sucrose intake by alcohol-preferring (P) rats and its association with GLT-1 expression. Neuroscience 326:117-25
Ding, Zheng-Ming; Ingraham, Cynthia M; Rodd, Zachary A et al. (2016) Alcohol drinking increases the dopamine-stimulating effects of ethanol and reduces D2 auto-receptor and group II metabotropic glutamate receptor function within the posterior ventral tegmental area of alcohol preferring (P) rats. Neuropharmacology 109:41-8
O'Tousa, David S; Grahame, Nicholas J (2016) Long-Term Alcohol Drinking Reduces the Efficacy of Forced Abstinence and Conditioned Taste Aversion in Crossed High-Alcohol-Preferring Mice. Alcohol Clin Exp Res 40:1577-85
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
Beckwith, Steven Wesley; Czachowski, Cristine Lynn (2016) Alcohol-Preferring P Rats Exhibit Elevated Motor Impulsivity Concomitant with Operant Responding and Self-Administration of Alcohol. Alcohol Clin Exp Res 40:1100-10
Qiu, Bin; Bell, Richard L; Cao, Yong et al. (2016) Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight. J Genet Genomics 43:421-30

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