Investigators of the Indiana Alcohol Research Center are world leaders in the development and characterization of selected lines of rodents for studies on alcohol preference and craving, the application of the alcohol clamp to permit precise control of blood alcohol levels, and the identification and study of genetic variants which influence responses to alcohol and risk of alcoholism. In the next period of support, we will 1) expand existing educational, collaborative research, and outreach activities on alcoholism for health and legal professionals around the world;2) continue selective breeding and provide rat (P/NP, HAD/LAD) and mouse (HAP/LAP) lines for Center investigators;3) provide genomic (expression profiling, real-time PCR confirmation of changes in mRNAs, high density SNP genotyping /haplotyping, ADH and ALDH genotyping) expertise for Center investigators and collaborators;4) correlate responses to alcohol, frontal lobe fMRI activity, pharmacokinetics, and factors that predict the risk for future alcoholism in subjects with family history of alcoholism and risk genotypes at the GABRA2 and ADH4 loci;5) examine mRNA expression profiles in the ventral tegmentum and accumbens-shell regions of P/NP and HAD/LAD rats during alcohol exposure paradigms;6) examine associations between high alcohol preference and sensitivity to nicotine and cocaine, and the effects of these drugs on alcohol responses;7) examine spatial and termporal patterns of embryonic gene expression in alcohol-exposed embryos, and relevant transcriptional mechanisms for these changes;8) support innovative pilot projects linked to the themes of the Center: functional brain imaging, 3 dimensional analysis of alcohol teratogenesis, genetics of response to naltrexone and of craving for alcohol, and alcohol teratogenesis in zebrafish;and 9) provide a rich environment for the training of undergraduate and graduate students, postdoctoral fellows, and visiting scientists. As a well-established Center, we will continue to mentor younger faculty for leadership roles in the Center and in the broader alcoholism research field.
These studies will provide better understanding of how genetic backgrounds affect responses to alcohol and other drugs of abuse, explanations for the sensitivity of the developing fetus to alcohol, and will seek to expand knowledge about alcoholism among health professionals and legal authorities, both in the US and around the world.
|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 andÂ 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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