Defining the Circuits of Ethanol Response

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于 临床观察到无节制的乙醇消费，至少有一种近亲繁殖 小鼠品系(C57BL/6J[B6])表现出较高的选择性和相对较高的选择性 与大多数标准近交系相比，每天的乙醇消耗量(12-20g/kg) 小鼠品系(例如DBA/2J[D2])。作为理解 与过度饮酒有关的机制，众多研究 专注于了解B6和D2毒株之间的差异 以及由这些菌株衍生的杂交和重组自交系(例如 Phillips等人。(1994年)。此应用程序构建于并扩展了这一行 研究。我们建议检验中央延伸杏仁核的假设 调节乙醇的偏好和消费；进一步建议 多巴胺能神经支配延伸的杏仁核是这一过程的中心。 起到调节作用。我们的具体目标领域如下：1)在B6和D2 菌株决定CEA和CEA中双侧电解性损伤的影响 关于乙醇偏好和消费的BSTL。2)在B6和D2中确定 双侧6-羟基多巴胺损毁CEA和BSTL对BSTL和CEA的影响 乙醇偏好和消费。3)确认显著差异 B6和D2间CEA和BST的DA神经支配模式 菌株。4)研究多巴胺受体的分布和密度 在B6和D2品系的延伸杏仁核内。5)确认 有选择地为高和低酒精消耗而饲养的动物，推定 DA表型(AIMS 2-4)与乙醇反应的关系。6)至 描述延伸的杏仁核和相关的多巴胺的作用 由该研究所开发的无控制乙醇消费新模型的表型 Inia财团。与这些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 对此作出回应，并将有助于印度国家情报机构联合体的总体目标， 即了解过量和无控制的酒精的神经生物学 消费。

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.