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.

National Institute of Health (NIH)
Research Project--Cooperative Agreements (U01)
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Study Section
Special Emphasis Panel (ZAA1)
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Egli, Mark
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Indiana University-Purdue University at Indianapolis
Schools of Medicine
United States
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Toalston, Jamie E; Deehan Jr, Gerald A; Hauser, Sheketha R et al. (2014) Reinforcing properties and neurochemical response of ethanol within the posterior ventral tegmental area are enhanced in adulthood by periadolescent ethanol consumption. J Pharmacol Exp Ther 351:317-26
Bell, Richard L; Rodd, Zachary A; Engleman, Eric A et al. (2014) Scheduled access alcohol drinking by alcohol-preferring (P) and high-alcohol-drinking (HAD) rats: modeling adolescent and adult binge-like drinking. Alcohol 48:225-34
McBride, William J; Kimpel, Mark W; McClintick, Jeanette N et al. (2014) Changes in gene expression within the extended amygdala following binge-like alcohol drinking by adolescent alcohol-preferring (P) rats. Pharmacol Biochem Behav 117:52-60
Sari, Y; Franklin, K M; Alazizi, A et al. (2013) Effects of ceftriaxone on the acquisition and maintenance of ethanol drinking in peri-adolescent and adult female alcohol-preferring (P) rats. Neuroscience 241:229-38
Getachew, Bruk; Hauser, Sheketha R; Dhaher, Ronnie et al. (2011) CB1 receptors regulate alcohol-seeking behavior and alcohol self-administration of alcohol-preferring (P) rats. Pharmacol Biochem Behav 97:669-75
Sari, Youssef; Sakai, Makiko; Weedman, Jason M et al. (2011) Ceftriaxone, a beta-lactam antibiotic, reduces ethanol consumption in alcohol-preferring rats. Alcohol Alcohol 46:239-46
Crabbe, John C; Bell, Richard L; Ehlers, Cindy L (2010) Human and laboratory rodent low response to alcohol: is better consilience possible? Addict Biol 15:125-44
Obara, Ilona; Bell, Richard L; Goulding, Scott P et al. (2009) Differential effects of chronic ethanol consumption and withdrawal on homer/glutamate receptor expression in subregions of the accumbens and amygdala of P rats. Alcohol Clin Exp Res 33:1924-34
Engleman, E A; Rodd, Z A; Bell, R L et al. (2008) The role of 5-HT3 receptors in drug abuse and as a target for pharmacotherapy. CNS Neurol Disord Drug Targets 7:454-67
Bell, Richard L; Rodd, Zachary A; Toalston, Jamie E et al. (2008) Autonomic activation associated with ethanol self-administration in adult female P rats. Pharmacol Biochem Behav 91:223-32

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