The overall objectives of this U01 research core application are to (a) provide selectively bred high ethanol (EtOH)-consuming rats that have experienced the drinking-in-dark (DID) EtOH binge-drinking protocol and their controls, or whole brains or brain sub-regions from these rats;and (b) use shRNAi's and other pharmacological tools to help identify genes, gene systems and receptors involved in the predisposition for, and development and maintenance of, EtOH binge-drinking. The overall hypothesis is that particular 'candidate'genes and their associated molecular networks within the extended amygdala and associated brain regions significantly contribute to the development and maintenance of, and a predisposition for, excessive EtOH drinking. The overall hypothesis will be tested by (a) providing alcohol-preferring (P) and high-alcohol-drinking (HAD) rats (or their whole brains or brain regions) that have been taken through the binge drinking protocol to other INIA U01 investigators;(b) using shRNAi's to reduce expression of 'candidate'genes within the extended amygdala and associated regions;and (c) examining the effects of ligands targeted for 'candidate'gene products and their molecular networks on, binge-drinking. Providing insight into the complex molecular and cellular events that lead to the development and maintenance of excessive alcohol drinking behavior in animal models is highly significant since these findings will provide the necessary foundation for developing novel treatment strategies targeting alcohol abuse and alcoholism. This is a highly innovative project since it will use state-of-the-art techniques to selectively reduce expression of 'candidate'genes in multiple genetically predisposed 'families'(i.e., the P, HAD1 and HAD2) of rats and in discrete CNS regions that are involved in regulating alcohol drinking. This U01 research core provides synergy with several INIA-West components by addressing the first two specific aims of INIA, i.e., confirm gene targets and identify drugable targets for medications focused on treating alcohol abuse and alcoholism.

Public Health Relevance

Alcohol abuse, alcoholism and their consequences continue to be the third leading cause of death in the U.S. Moreover, alcohol binge-drinking among today's youth and young adults is a major public health concern. Understanding the molecular neurobiological events mediating alcohol abuse or a genetic predisposition for this behavior continues to aid in the development of treatments for alcohol use disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA013522-14
Application #
8716605
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Egli, Mark
Project Start
2001-09-27
Project End
2016-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
14
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Ding, Zheng-Ming; Ingraham, Cynthia M; Hauser, Sheketha R et al. (2017) Reduced Levels of mGlu2 Receptors within the Prelimbic Cortex Are Not Associated with Elevated Glutamate Transmission or High Alcohol Drinking. Alcohol Clin Exp Res 41:1896-1906
Reno, James M; Thakore, Neha; Cormack, Lawrence K et al. (2017) Negative Affect-Associated USV Acoustic Characteristics Predict Future Excessive Alcohol Drinking and Alcohol Avoidance in Male P and NP Rats. Alcohol Clin Exp Res 41:786-797
Harris, R Adron; Bajo, Michal; Bell, Richard L et al. (2017) Genetic and Pharmacologic Manipulation of TLR4 Has Minimal Impact on Ethanol Consumption in Rodents. J Neurosci 37:1139-1155
Mittal, N; Thakore, N; Bell, R L et al. (2017) Sex-specific ultrasonic vocalization patterns and alcohol consumption in high alcohol-drinking (HAD-1) rats. Physiol Behav :
Bell, Richard L; Hauser, Sheketha R; Liang, Tiebing et al. (2017) Rat animal models for screening medications to treat alcohol use disorders. Neuropharmacology 122:201-243
Weera, Marcus M; Fields, Molly A; Tapp, Danielle N et al. (2017) Effects of Nicotine on Alcohol Drinking in Female Mice Selectively Bred for High or Low Alcohol Preference. Alcohol Clin Exp Res :
Dir, Allyson L; Bell, Richard L; Adams, Zachary W et al. (2017) Gender Differences in Risk Factors for Adolescent Binge Drinking and Implications for Intervention and Prevention. Front Psychiatry 8:289
Bell, Richard L; Hauser, Sheketha R; McClintick, Jeanette et al. (2016) Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings. Prog Mol Biol Transl Sci 137:41-85
Thakore, Neha; Reno, James M; Gonzales, Rueben A et al. (2016) Alcohol enhances unprovoked 22-28 kHz USVs and suppresses USV mean frequency in High Alcohol Drinking (HAD-1) male rats. Behav Brain Res 302:228-36
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

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