Human Alcohol Seeking Despite Aversion Prolonged alcohol use results in neuroadaptations leading to decreased sensitivity to alcohol, a shift from positive to negative reinforcement-based alcohol use, increased negative affect that drives further consumption, and, ultimately, aversion-resistant drinking. Aversion resistant drinking is a hallmark of more severe and treatment-resistant persistent alcohol use. It has been widely studied in animal models, but has not been well characterized in humans. This project aims to develop an objective measure of aversion resistant drinking in humans, modeled as alcohol self-administration despite aversion, and to characterize its underlying neural signatures. The positive impact of this project will be to advance the translation between preclinical models and clinical models, and to elucidate distinct mechanisms underlying alcohol use disorder progression in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
2P60AA007611-31
Application #
9393543
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
31
Fiscal Year
2018
Total Cost
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

Showing the most recent 10 out of 280 publications