Defining the Circuits of Ethanol Response

定义乙醇反应回路

• 批准号: 6533690
• 负责人: ROBERT J. HITZEMANN
• 金额: $ 19万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-27 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6533690
• 关键词: 6 hydroxydopamine; alcoholic beverage consumption; amygdala; autoradiography; behavioral /social science research tag; brain regulatory center; cooperative study; dopamine receptor; dopamine transporter; ethanol; experimental brain lesion; gene expression; gene targeting; genetically modified animals; immunocytochemistry; in situ hybridization; laboratory mouse; preference; receptor expression; substance abuse related behavior; western blottings

DESCRIPTION (provided by applicant): While there is general agreement that no rodent model approximates the uncontrolled consumption of ethanol observed clinically, at least one inbred strain of mice (the C57BL/6J [B6]) shows a high preference and relatively high daily consumption of ethanol (12-20g/kg) compared to most standard inbred mouse strains (e.g. the DBA/2J [D2]). As a first step to understanding the mechanisms associated with excessive alcohol consumption, numerous studies have focused on understanding the differences between the B6 and D2 strains and intercrosses and recombinant inbreds derived from these strains (e.g. Phillips et al. 1994). This application builds from and expands this line of research. We propose to test the hypothesis that the central extended amygdala modulates ethanol preference and consumption; it is further proposed that the dopaminergic innervation to the extended amygdala is central to this modulatory role. Our specific aims areas follows: 1) To in the B6 and D2 strains determine the effects of bilateral electrolytic lesions in the CeA and BSTL on ethanol preference and consumption. 2) To determine in the B6 and D2 strains the effects of Bilateral 6-OH DA lesions in the CeA and BSTL on ethanol preference and consumption. 3) To confirm the marked differences in the pattern of DA innervation in the CeA and BST between the B6 and D2 strains. 4) To characterize the distribution and density of dopamine receptors within the extended amygdala in the B6 and D2 strains. 5) To confirm in animals selectively bred for high and low ethanol consumption, the putative relationships between DA phenotypes (aims 2-4) and ethanol response. 6) To characterize the role of the extended amygdala and the associated DA phenotypes in new models of uncontrolled ethanol consumption developed by the INIA consortium. The experiments associated with each of these aims should provide important new information about the circuits associated with ethanol response and will contribute to the overall goal of the INIA consortium, namely to understand the neurobiology of excessive and uncontrolled ethanol consumption.

描述（由申请人提供）： 虽然人们普遍认为没有啮齿动物模型可以近似 临床上观察到的乙醇消耗不受控制，至少有一种近交系 小鼠品系（C57BL/6J [B6]）表现出较高的偏好度和相对较高的 与大多数标准近交系相比，每日乙醇消耗量 (12-20g/kg) 小鼠品系（例如 DBA/2J [D2]）。作为理解的第一步 与过量饮酒相关的机制，大量研究 重点了解 B6 和 D2 菌株之间的差异 以及源自这些菌株的杂交和重组自交系（例如 菲利普斯等人。 1994）。该应用程序构建并扩展了该系列 研究。我们建议检验中央扩展杏仁核的假设 调节乙醇偏好和消费；进一步建议 扩展杏仁核的多巴胺能神经支配是这一点的核心 调节作用。我们的具体目标领域如下： 1) 达到 B6 和 D2 菌株决定了 CeA 中双侧电解损伤的影响 关于乙醇偏好和消费的 BSTL。 2）在B6和D2中确定 应变 CeA 和 BSTL 中双侧 6-OH DA 损伤的影响 乙醇偏好和消费。 3) 确认显着差异 CeA 和 BST 中 B6 和 D2 之间的 DA 神经支配模式 菌株。 4) 表征多巴胺受体的分布和密度 在 B6 和 D2 品系的扩展杏仁核内。 5) 确认 选择性饲养高乙醇消耗和低乙醇消耗的动物，假定 DA 表型（目标 2-4）和乙醇反应之间的关系。 6) 到 描述扩展杏仁核和相关 DA 的作用 开发的不受控制的乙醇消费新模型的表型 INIA 财团。与每个目标相关的实验应该 提供有关乙醇相关电路的重要新信息 响应并将为 INIA 联盟的总体目标做出贡献， 即了解过量和不受控制的乙醇的神经生物学 消耗。