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.
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.
|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