Research Component # 3, entitled "Post-Abstinence Response Drinking in Humans" will assess the effect of 2 weeks of monitored abstinence from usual drinking habits on post-abstinence response (PAR) dnnking using an operant alcohol self-administration paradigm. The sample population is 60 healthy Caucasian, young- adult, heavy drinkers. The central hypotheses are that short term abstinence from alcohol will increase PAR in binge-style dnnkers, compared to those who consume a similar quaiitity over time, but on a regular basis, and that PAR will be greater in those with positive family of alcoholism compared to controls. We will also explore a panel of candidate genes, the personal history of externalizing behaviors, and changes in metabolic capacity for eliminating alcohol for potential associations with PAR. PAR will be assessed in a 3-session, within-subjects, between-group design using the Progressive Work Paradigm of the Computer-Assisted Self-Administration of Ethanol (CASE) system developed by the lARC and validated in Pilot Study 53 of the current research cycle. The first session will provide familiarity with the procedures, and the second and third sessions will be conducted on the days that bracket 2 weeks of monitored abstinence from the subject's usual drinking habits. Indices of the subject's maximal willingness to perform increasing amounts of work to earn immediate delivery of another alcohol reward, and the subjective perceptions of craving and alcohol effects will provide the dependent measures for analysis. The combination of intravenous alcohol delivery and physiologically-based pharmacokinetic modeling of individual subjects that is employed by CASE insures that, unlike oral alcohol administration, the incremental time course of brain exposure to alcohol will be the same for each reward in every subject, and will be free of expectancies associated with sight, taste and odor. We expect the research to establish a new endophenotype for alcoholism risk, PAR;enabling future research on the influence of specific genes and/or epigenetic mediators, PAR's neural substrates, the efficacy of pharmaceuticals on blunting development of binge dnnking, and the interaction of abstinence from alcohol with use of other drugs.

Public Health Relevance

How bnef intervals of abstinence from alcohol can result in increased intake when drinking resumes has been studied in animal models but not in humans. Such a study could build the foundation for understanding why binge drinking greatly increases the risk for developing future alcohol use disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
2P60AA007611-26
Application #
8400537
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
$153,520
Indirect Cost
$55,110
Name
Indiana University-Purdue University at Indianapolis
Department
Type
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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