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.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Comprehensive Center (P60)
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Special Emphasis Panel (ZAA1-GG (50))
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Indiana University-Purdue University at Indianapolis
United States
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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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