The long-range goals of this project are to better understand the response and consequences of drugs of abuse on subjects that are genetically vulnerable to high alcohol drinking. This is an important area of research in the alcohol field, because many, a large majority in the case of nicotine, individuals who abuse or are dependent on alcohol also abuse other drugs. Moreover, there is evidence that nicotine or cocaine can promote alcoholic relapse and have neurobiological interactions with alcohol. The overall hypotheses to be tested are that (1) selective breeding for disparate alcohol drinking will also produce disparate responses to the effects of other drugs of abuse, and (2) prior exposure to other drugs of abuse will have effects on alcohol drinking and the reinforcing effects of alcohol that are genetically influenced. These hypotheses will be tested in the selectively bred alcohol-preferring (P), alcohol-non-preferring (NP), high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) lines of rats. The objectives of this proposal are to examine the effects of nicotine and cocaine on locomotor activity, alcohol drinking and reinforcement, and mesolimbic dopamine (DA) activity of the selectively bred lines of rats. The results of this study will provide important information on how genetic factors influence a predisposition for high alcohol drinking and abusing other drugs, and how genetic factors that influence alcohol drinking react to other drugs of abuse. Such information could provide insight into common factors that might influence vulnerability to drug and alcohol abuse in certain human populations. This research component interacts with and is dependent upon the Administrative and Animal Production Cores, and also scientifically interacts with the other rat genetic research component. This research component fits within the theme of the IARC in that it is studying genetic effects on the actions of nicotine and cocaine to alter alcohol drinking and the reinforcing effects of ethanol (EtOH).

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Comprehensive Center (P60)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1-BB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Indiana University-Purdue University at Indianapolis
United States
Zip Code
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

Showing the most recent 10 out of 267 publications