Center on Genetic Determinants of Alcohol Ingestion and Responses to Alcohol

酒精摄入和酒精反应的遗传决定因素中心

• 批准号: 7778058
• 负责人: DAVID W CRABB
• 金额: $ 14.08万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7778058
• 关键词: Affect; Alcohol abuse; Alcohol consumption; Alcoholism; Alcohols; Amino Acid Sequence; Animal Experiments; Animal Model; Animals; Antisocial Personality Disorder; Behavior; Behavioral; Biodiversity; Blood alcohol level measurement; Boutos; Brain; Brain imaging; Breeding; Budgets; Calcium; Cell Nucleus; Cell physiology; Cells; Clinical; Cocaine; Collaborations; Complex; Conduct Disorder; Consumption; Cyclic Nucleotides; Cytoskeleton; Dependence; Development; Disinhibition; Dopamine; Drug Kinetics; EP300 gene; Educational Activities; Electroencephalography; Embryo; Environment; Environmental Risk Factor; Esthesia; Ethanol; Experimental Models; Faculty; Family history of; Fetal Alcohol Syndrome; Fetal alcohol effects; Fetus; Fostering; Functional Magnetic Resonance Imaging; Funding; Funding Mechanisms; Future; Gene Expression; Gene Proteins; Genes; Genetic; Genetic Determinism; Genetic Risk; Genetic Transcription; Genetic Variation; Genomics; Genotype; Goals; Grant; Health; Health Professional; Human; Human Genetics; Indiana; Individual; Interdisciplinary Study; International; Intoxication; Investigation; Kenya; Knowledge; Leadership; Legal; Link; Longevity; Measures; Mentors; Messenger RNA; Metabolism; Modeling; Molecular; Molecular Biology; Molecular Profiling; Mus; Mutation; Naltrexone; Nervous system structure; Neural Pathways; Neurobiology; Neurons; Neuropeptides; Nicotine; Nurses; Opioid; Outreach Research; Pathogenesis; Pathway interactions; Pattern; Performance; Personality Traits; Pharmaceutical Preparations; Pharmacodynamics; Phenotype; Phosphoric Monoester Hydrolases; Physiology; Pilot Projects; Postdoctoral Fellow; Predisposition; Process; Production; Protein Kinase; Proteins; Proteome; Proteomics; Rattus; Regulation; Research; Research Personnel; Research Support; Resources; Retinoids; Risk; Risk Factors; Rodent; Role; SNP genotyping; Saccades; Sampling; Scientist; Second Messenger Systems; Serotonin; Services; Signal Pathway; Signal Transduction; Social Workers; Technology; Testing; Three-dimensional analysis; Time; Training; Translational Research; Universities; Variant; Ventral Tegmental Area; Visit; Work; Zebrafish; alcohol and other drug; alcohol craving; alcohol exposure; alcohol preferring rats; alcohol research; alcohol response; alcohol risk; alcohol seeking behavior; aldehyde dehydrogenases; animal breeding; authority; craving; density; deprivation; drinking; drinking behavior; drug of abuse; endophenotype; frontal lobe; functional genomics; genetic analysis; genetic variant; graduate student; improved; innovation; mRNA Expression; mRNA Stability; multidisciplinary; neuroimaging; neuropeptide Y; neuropsychological; neurotransmitter release; neurotrophic factor; outreach; paracrine; preference; programs; protein function; psychologic; public health relevance; relating to nervous system; response; science education; second messenger; social; trait; transcription factor

DESCRIPTION (provided by applicant): 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. Public Health Relevance: 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.

描述（由申请人提供）：印第安纳州酒精研究中心的研究人员是世界领先的开发和表征选定的啮齿动物系的研究酒精偏好和渴望，酒精钳的应用，以允许精确控制血液酒精水平，并识别和研究影响酒精反应和酒精中毒风险的遗传变异。在下一阶段的支持中，我们将1）为世界各地的健康和法律的专业人员扩大现有的关于酗酒的教育、合作研究和外展活动; 2）继续选择性繁殖，并提供大鼠（P/NP、HAD/LAD）和小鼠（HAP/LAD）系供中心研究者使用; 3）提供基因组（表达谱分析、mRNA变化的实时PCR确认、高密度SNP基因分型/单体型分型、ADH和ALDH基因分型）中心研究者和合作者的专业知识; 4）在有酒精中毒家族史和GABRA 2和ADH 4基因座的风险基因型的受试者中，将对酒精的反应、额叶fMRI活性、药代动力学和预测未来酒精中毒风险的因素相关联; 5）在酒精暴露范例期间，检测P/NP和HAD/LAD大鼠腹侧被盖和小脑壳区域的mRNA表达谱; 6）研究高度酒精偏好与尼古丁和可卡因敏感性之间的关系，以及这些药物对酒精反应的影响; 7）研究暴露于酒精的胚胎中胚胎基因表达的空间和时间模式，以及这些变化的相关转录机制; 8）支持与中心主题相关的创新试点项目：功能性脑成像，酒精致畸作用的三维分析，对纳洛酮的反应和对酒精的渴望的遗传学，以及斑马鱼的酒精致畸作用;和9）为本科生和研究生，博士后研究员和访问科学家的培训提供丰富的环境。作为一个完善的中心，我们将继续指导年轻的教师在中心和更广泛的酗酒研究领域的领导作用。 公共卫生相关性：这些研究将更好地了解遗传背景如何影响对酒精和其他滥用药物的反应，解释发育中的胎儿对酒精的敏感性，并将寻求扩大美国和世界各地的卫生专业人员和法律的当局对酒精中毒的了解。