Endophenotypes for Differential Ethanol-seeking and Drinking (IMP)

差异乙醇寻求和饮用 (IMP) 的内表型

• 批准号: 8601003
• 负责人: CRISTINE L CZACHOWSKI
• 金额: $ 13.58万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8601003
• 关键词: Address; Alcohol consumption; Alcoholism; Alcohols; Behavior; Behavioral; Behavioral Paradigm; Behavioral inhibition; Brain region; Breeding; Cognitive; Disease; Ethanol; Exhibits; Genetic; Genetic Determinism; Goals; Heavy Drinking; Human; Impulsive Behavior; Impulsivity; Intervention; Lead; Long-Evans Rats; Measures; Modeling; Motivation; Motor; Neurotransmitters; Pattern; Pharmaceutical Preparations; Phenotype; Population; Rattus; Reaction; Recording of previous events; Rodent; Self Administration; Self-Administered; Signal Transduction; Sucrose; System; alcohol craving; alcohol exposure; alcohol reinforcement; alcohol research; alcohol response; alcohol seeking behavior; binge drinking; discounting; drinking; drinking behavior; endophenotype; non-drug; preference; reinforcer; trait

Alcoholism is a heterogeneous disorder, with different subtypes of behaviors both predisposing and exacerbating alcohol craving and drinking. While the alcohol research field has been successful in selectively breeding rodent lines that prefer and voluntarily consume large quantities of alcohol, there remains a critical need to understand the mechanisms by which different genetic histories and endophenotypic behavioral paths lead to a common phenotype of high drinking. This component will examine a largely unaddressed question: What behaviors distinguish high-alcohol preferring rodent lines from each other? Our rationale is that while alcohol-preferring (P) and high alcohol drinking (HAD) rats were selectively bred for the same behavioral phenotype (ethanol preference), they differ In behaviors associated with both motor and cognitive impulsivity that precede any ethanol exposure. A behavioral paradigm that separates ethanol-seeking and self-administration (Czachowski & Samson, 1999; 2002) shows different patterns of ethanol-motivated responding in three rat populations. We will determine If the different seeking/drinking,patterns are related to differences in impulsivity. Our long-term goals are to understand the relationship between impulsivity and drinking behavior and to develop pharmacologic interventions that target the impulsivity phenotypes as a way to control drinking. The short-term goals of this proposal are to identify: 1) impulsive endophenotypes in two lines of rats considered as good models of human alcoholism, and 2) brain region/neurotransmitter systems Involved in both impulsivity and ethanol reinforcement. This will be addressed in 3 specific aims: SA1. Characterize impulsivity as measured by impaired behavioral inhibition (motor impulsivity) and impulsive choice (cognitive impulsivity) in P, HAD, and Long Evans rats that differentially express the motivation to seek and self-administer ethanol, using a natural reinforcer (sucrose). SA2. Determine the degree to which measures of Impulsivity are exhibited with reinforcers in general, or If they are specific to ethanol. SAS. Assess the effects of pharmacologic manipulation of frontal cortical function on impulsivity phenotypes and ethanol-seeking and drinking.

酗酒是一种异质性疾病，具有不同的行为亚型，既诱发酒精中毒，又导致酒精中毒。 加剧对酒精的渴望和饮酒。虽然酒精研究领域已经成功地有选择地 培育喜欢并自愿消耗大量酒精的啮齿动物品系，仍然存在一个关键问题 需要了解不同遗传历史和内表型行为的机制 路径导致了酗酒的常见表型。该组件将检查一个很大程度上未解决的问题 问题：哪些行为可以将喜欢高酒精度的啮齿动物系与其他啮齿动物系区分开来？我们的理由是 嗜酒（P）和大量饮酒（HAD）大鼠是为了相同的目的而选择性饲养的 行为表型（乙醇偏好），它们在与运动和认知相关的行为方面有所不同 任何乙醇暴露之前的冲动。一种将乙醇寻求与乙醇分离的行为范式 自我给药（Czachowski & Samson，1999；2002）显示出不同的乙醇驱动模式 在三个大鼠群体中做出反应。我们将确定不同的寻找/饮酒模式是否与 冲动性的差异。我们的长期目标是了解冲动和冲动之间的关系 饮酒行为并开发针对冲动表型的药物干预措施 控制饮酒的方法。该提案的短期目标是确定：1​​）冲动内表型 两种大鼠系被认为是人类酗酒的良好模型，以及 2) 大脑区域/神经递质 系统涉及冲动和乙醇强化。这将通过 3 个具体目标来解决： SA1。通过行为抑制受损（运动冲动）来衡量冲动性的特征，以及 P、HAD 和 Long Evans 大鼠的冲动选择（认知冲动）差异表达 使用天然强化剂（蔗糖）寻求和自我施用乙醇的动机。 SA2。确定 一般来说，强化物表现出冲动性的程度，或者如果它们是特定的 乙醇。 SAS。评估额叶皮质功能的药物操作对冲动的影响 表型与乙醇寻求和饮酒。