Alcoholism is a heterogeneous disorder, with different subtypes of behaviors both predisposing and exacerbating alcohol craving and drinking. While the alcohol research field has been successful in selectively breeding rodent lines that prefer and voluntarily consume large quantities of alcohol, there remains a critical need to understand the mechanisms by which different genetic histories and endophenotypic behavioral paths lead to a common phenotype of high drinking. This component will examine a largely unaddressed question: What behaviors distinguish high-alcohol preferring rodent lines from each other? Our rationale is that while alcohol-preferring (P) and high alcohol drinking (HAD) rats were selectively bred for the same behavioral phenotype (ethanol preference), they differ In behaviors associated with both motor and cognitive impulsivity that precede any ethanol exposure. A behavioral paradigm that separates ethanol-seeking and self-administration (Czachowski &Samson, 1999;2002) shows different patterns of ethanol-motivated responding in three rat populations. We will determine If the different seeking/drinking,patterns are related to differences in impulsivity. Our long-term goals are to understand the relationship between impulsivity and drinking behavior and to develop pharmacologic interventions that target the impulsivity phenotypes as a way to control drinking. The short-term goals of this proposal are to identify: 1) impulsive endophenotypes in two lines of rats considered as good models of human alcoholism, and 2) brain region/neurotransmitter systems Involved in both impulsivity and ethanol reinforcement. This will be addressed in 3 specific aims: SA1. Characterize impulsivity as measured by impaired behavioral inhibition (motor impulsivity) and impulsive choice (cognitive impulsivity) in P, HAD, and Long Evans rats that differentially express the motivation to seek and self-administer ethanol, using a natural reinforcer (sucrose). SA2. Determine the degree to which measures of Impulsivity are exhibited with reinforcers in general, or If they are specific to ethanol. SAS. Assess the effects of pharmacologic manipulation of frontal cortical function on impulsivity phenotypes and ethanol-seeking and drinking.

Public Health Relevance

This project will identify impulsive endophenotypes in two lines of rats considered as good models of human alcoholism, as well as the underlying brain region/neurotransmitter systems Involved in regulating both impulsivity and alcohol reinforcement The goal is to understand the relationship between impulsivity and binge-drinking behavior and to develop pharmacologic interventions that target the impulsivity phenotypes as a way to control alcohol drinking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
5P60AA007611-27
Application #
8601003
Study Section
Special Emphasis Panel (ZAA1-GG)
Project Start
Project End
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
27
Fiscal Year
2014
Total Cost
$126,037
Indirect Cost
$45,350
Name
Indiana University-Purdue University at Indianapolis
Department
Type
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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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
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