Alcoholism is caused by a complex interaction of environmental, genetic, and physiological factors. A family history of alcoholism is a strong predictor of high alcohol seeking behavior in humans and in animal models of alcoholism, and the prognosis is worse when an individual has a both high genetic load for alcoholism and a personal history of alcohol use. This proposal seeks a better understanding of neural mechanisms that are altered by alcohol experience. The populations of mice that will be used in this project already show evidence of a link between behavioral sensitization to alcohol's locomotor stimulating effects and alcohol drinking. ? Specifically, these selectively bred, High Alcohol Preferring (HAP) mice are more likely to show locomotor sensitization (LMS) to ethanol following repeated administration than Low Alcohol Preferring (LAP) mice, indicating that LMS and drinking are likely to be genetically and physiologically linked. Investigating mechanisms underlying LMS may yield insight into the mechanisms of high alcohol drinking. This proposal directly seeks evidence about neural pathways involved in LMS and its relationship to excessive drinking by studying immediate early gene expression. Experiments will also assess whether exposure to alcohol sufficient to induce LMS increases either the incentive value of alcohol and/or alcohol drinking. Finally, because enduring LMS in HAP mice requires that they associate their test environment with previous alcohol injections, studies will seek to understand whether the memory of alcohol affects alcohol drinking and the incentive value of alcohol. One study will also test whether acamprosate, a treatment for alcoholism, can reverse changes in the rewarding value of alcohol caused by alcohol exposure. The hypothesis is that associative forms of neural and behavioral plasticity underlie both the acquisition of excessive drinking and LMS, and that the amygdala may lie at the heart of this interaction. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA013483-06
Application #
7277836
Study Section
Special Emphasis Panel (ZAA1-DD (30))
Program Officer
Egli, Mark
Project Start
2001-09-27
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
6
Fiscal Year
2007
Total Cost
$236,541
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Oberlin, Brandon; Best, Christina; Matson, Liana et al. (2011) Derivation and characterization of replicate high- and low-alcohol preferring lines of mice and a high-drinking crossed HAP line. Behav Genet 41:288-302
Lopez, Marcelo F; Grahame, Nicholas J; Becker, Howard C (2011) Development of ethanol withdrawal-related sensitization and relapse drinking in mice selected for high- or low-ethanol preference. Alcohol Clin Exp Res 35:953-62
Oberlin, Brandon G; Bristow, Robert Evan; Heighton, Meredith E et al. (2010) Pharmacologic dissociation between impulsivity and alcohol drinking in high alcohol preferring mice. Alcohol Clin Exp Res 34:1363-75
Oberlin, B G; Grahame, N J (2009) High-alcohol preferring mice are more impulsive than low-alcohol preferring mice as measured in the delay discounting task. Alcohol Clin Exp Res 33:1294-303
Green, Alexis S; Grahame, Nicholas J (2008) Ethanol drinking in rodents: is free-choice drinking related to the reinforcing effects of ethanol? Alcohol 42:1-11
Mulligan, Megan K; Ponomarev, Igor; Hitzemann, Robert J et al. (2006) Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis. Proc Natl Acad Sci U S A 103:6368-73
Bachtell, Ryan K; Weitemier, Adam Z; Galvan-Rosas, Agustin et al. (2003) The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption. J Neurosci 23:2477-87