Rodents with Genetic Differences in Alcohol Preference

酒精偏好有遗传差异的啮齿类动物

• 批准号: 8269148
• 负责人: LAWRENCE LUMENG
• 金额: $ 59.1万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8269148
• 关键词: 4-aminospiroperidol; Abstinence; Administrative Supplement; Alcohol consumption; Alcohol dependence; Alcoholism; Alcohols; Amphetamine Abuse; Animal Model; Antisocial Personality Disorder; Anxiety; Anxiety Disorders; Behavior; Behavioral; Biological Markers; Breeding; Candidate Disease Gene; Cannabis Abuse; Cell Nucleus; Characteristics; Charge; Chronic; Cigarette Smoker; Comorbidity; Complex; Dependence; Disease; Dopamine; Drug Use Disorder; Drug abuse; Endocannabinoids; Environmental Risk Factor; Exhibits; Finland; Foundations; Funding; Funding Agency; Generalized Anxiety Disorder; Genes; Genetic; Genetic Load; Genetic Predisposition to Disease; Heavy Drinking; Heritability; Heterogeneity; Human; Human Resources; Hybrids; Inbreeding; Indiana; Individual; Instinct; Instruction; Intervention; Intravenous; Laboratories; Maintenance; Modeling; Monoclonal Antibody R24; Mus; National Institute on Alcohol Abuse and Alcoholism; Nicotine; Opioid; Panic Attack; Panic Disorder; Pathway interactions; Phenotype; Physiological; Population; Principal Investigator; Process; Progress Reports; Psychiatry; Rat Strains; Rattus; Relapse; Reporting; Research; Research Personnel; Resources; Respondent; Risk-Taking; Rodent; Route; Sampling; Self Administration; Self-Administered; Shelter facility; Simulate; Smoker; Spain; Staging; Testing; Time; Translational Research; United States National Institutes of Health; Universities; Wisconsin; Wistar Rats; addiction; alcohol misuse; alcohol preferring rats; alcohol relapse; alcohol research; anti social; cost; deprivation; drinking; genetic risk factor; help-seeking behavior; human APEX1 protein; interest; medical schools; member; middle age; nicotine abuse; pre-clinical research; preference; problem drinker; professor; programs; psychosocial; willingness

DESCRIPTION (provided by applicant): The major objective of this R24 Alcohol Research Resource nt is to supply to off-campus researchers at cost P/NP, HAD1-2/LAD1-2, and AA/ANA selectively bred rats, as well as HAP1-2-3/LAP2-3 and cHAP selected mice that show genetically high and/or low alcohol preference. (Specific Aims 2 and 3). The P/NP, HAD1-2/LAD1-2, HAP1-2-3/LAP2-3, and cHAP selected rodent lines were developed at Indiana University and this R24 is the sole funding source for maintaining the HAD1-2/LAD1-2 nucleus breeding colonies (Specific Aim 1). The HADl- 2/LAD1-2 lines from the N/Nih foundation stock are the only replicate rat lines selectively bred for divergent alcohol preference and they are phenotypically and genotypically different from the P/NP contrasting lines. In order to increase the value of this R24, a breeding colony ofAA/ANA rat lines will be transferred from Finland to Indiana as a new resource (Specific Aim 4). Neurochemically, AA rats are strikingly different from P rats, i.e., the mesolimbic dopamine pathway is not central either in the acquisition or maintenance of high alcohol preference in the AA rats; instead, innate neurocircuitries that involve endogeneous opioids and endocannabinoids appear to be the key. For the purpose of bringing further added value to this R24, Duke University will receive a subcontract to collaborate in creating a valid animal model of alcohol and nicotine co-abuse (Specific Aim 5). This approach is most expedient because Dr. Ting-Kai Li (the PI who created our P/NP, HAD1-2/LAD1-2, and HAP1-2/LAP1-2 selected rodent lines) is now a Professor of Psychiatry at Duke and Drs. Amir H. Rezvani and Edward D. Levin have active research programs at Duke that use iv nicotine self-administration routinely. This will be achieved by first comparing the five pairs of selectively bred rat lines with opposite alcohol preference (i.e., P/NP, HADl/LADl, HAD2/LAD2, AA/ANA, and sP/sNP) for their differences in willingness to self- administer nicotine by intraveneous route and to identify which high line has the highest proclivity to self- administer nicotine. This high line with both high alcohol drinking preference and high nicotine iv self- administration will then be used to investigate the effects of nondependent alcohol drinking and relapse-like alcohol drinking on nicotine self-administration. RELEVANCE (See instructions): Multiple alcohol-preferring rat lines from different genetic background are available, and together, they simulate behaviorally the distinct subtypes of alcoholics with high genetic load defined by a recent NESARC study. This R24 will supply to off-campus researchers the P/NP, HAD1-2/LAD1-2, and AA/ANA selectively bred rats as well as the HAP1-2-3/LAP2-3 and cHAP selected mice. Additionally, this R24 will create a new animal model of alcohol-nicotine co-abuse that will be extremely useful in basic preclinical research.

描述（由申请人提供）：R24酒精研究资源的主要目标是以P/NP的成本为P/NP，HAD1-2/LAD1-2和AA/ANA选择性地育种大鼠，以及HAP1-2-3/LAP2-3和CHAP选择的小鼠，以遗传性高和/或低酒精的优先供应。 （特定目标2和3）。 P/NP，HAD1-2/LAD1-2，HAP1-2-3/LAP2-3和CHAP选定的啮齿动物线是在印第安纳大学开发的，该R24是维持HAD1-2/LAD1-2核育种菌落的唯一资金来源（特定目标1）。 N/NIH基础库存中的HADL-2/LAD1-2线是唯一选择性地繁殖出用于发散酒精偏好的大鼠线，它们在表型和基因型上与P/NP的对比截然不同。为了提高此R24的价值，将从芬兰转移到印第安纳州的繁殖菌落，作为一种新资源（特定的AIM 4）。在神经化学上，AA大鼠与P大鼠明显不同，即中脱甲贝胺的多巴胺途径在AA大鼠中获得或维持高酒精偏好方面都不是中心的。取而代之的是，涉及内生阿片类药物和内源性大麻素的先天神经记录似乎是关键。为了为这一R24带来进一步的增值，杜克大学将获得分包合同，以合作创建有效的酒精和尼古丁共同滥用动物模型（特定的AIM 5）。 这种方法是最方便的，因为Ting-kai Li博士（创建我们的P/NP的PI，HAD1-2/LAD1-2和HAP1-2/LAP1-2选择的啮齿动物系列）现在是Duke and Drs的精神病学教授。阿米尔·H·雷兹瓦尼（Amir H.这将通过首先将相反的酒精偏好（即P/NP，HADL/LADL，HADL/LADL，HAD2/LAD2，AA/ANA和SP/SNP）进行比较，以进行相反的繁殖大鼠系列来实现这一目标，以了解它们愿意通过固定路线进行自我管理的尼古丁的差异，并确定哪个高线具有自我管理的nicotine nicotine nicotine nicotine nicotine。然后将使用高酒精饮酒偏好和高尼古丁IV自我给药的高线来研究非依赖性饮酒和类似复发的饮酒对尼古丁自我给药的影响。 相关性（请参阅说明）：可获得来自不同遗传背景的多种饮酒大鼠线，并且在最近的NESARC研究中，它们在行为上模拟了具有高遗传负荷的酗酒者的不同亚型。该R24将向校外研究人员提供P/NP，HAD1-2/LAD1-2和AA/ANA选择性地育种大鼠以及HAP1-2-3/LAP2-3和CHAP SELECT选择的小鼠。此外，该R24将创建一种新的饮酒型葡萄糖动物模型，该模型将在基本的临床前研究中非常有用。