Indiana Genetic Animal Models Core

描述（由申请人提供）： 这项研究的长期目标是研究神经适应性 在杏仁核及其相互联系中， 酒精在大鼠体内的消耗一系列的实验将确保 过量乙醇大鼠的质量控制和有效性 饮酒动物模型为此，高酒精消费的P和HAD (both重复线）大鼠将通过乙醇饮用方案 包括暴露于多种乙醇浓度的重复循环 然后是一段时间的剥夺。第二系列实验将 通过评估进一步表征和改进乙醇饮用方案， 改变初始和后续乙醇的长度的影响 暴露和2）剥夺和改变可用的乙醇 浓度的第三个系列的实验将研究这种影响， 乙醇供应和剥夺循环的实验范式已经在 低酒精消耗的饮酒模式（例如，NP、LAD-1、LAD-2和 Wistar）大鼠。酒精饮用协议导致非常高水平的 P和HAD大鼠的乙醇摄入量（恢复时高达16 g/kg/天） 暴露三个周期后的多个浓度的乙醇， 剥夺），这表明乙醇的增强特性可能具有 被增强了。要检验的主要假设是， 过量饮酒会导致神经适应性改变， 延伸杏仁核及其相互联系老鼠线已经被 在印第安纳州大学遗传选择高酒精饮用（即，P、 已知HAD-1和HAD-2）在以下情况下表现出“失控”饮酒， 暴露于该计划中提出的乙醇饮用协议。的 该提案的结果将提供有价值的信息， 了解过量饮酒的神经回路， 酗酒复发。这些信息对以下方面很重要： 开发治疗酒精中毒和酒精的药物疗法 虐待

DESCRIPTION (provided by applicant): The long-term objective of this research is to investigate neuroadaptations within the extended amygdala and its interconnections following excessive ethanol consumption in rats. One series of experiments will ensure the quality control and availabity of rats taken through the excessive ethanol drinking animal model. Towards this end, high-alcohol-consuming P and HAD (both replicate lines) rats will be taken through an ethanol drinking protocol involving repeated cycles of exposure to multiple ethanol concentrations followed by a period of deprivation. A second series of experiments will further characterize and refine the ethanol drinking protocol by evaluating the effects of altering the length of initial and subsequent 1) ethanol exposures and 2) deprivations and changing the available ethanol concentrations. A third series of experiments will examine the influence this experimental paradigm of cycles of ethanol availability and deprivation has in the drinking pattern of low-alcohol-consuming (e.g., NP, LAD-1, LAD-2 and Wistar) rats. The ethanol drinking protocol results in very high levels of ethanol intake in P and HAD rats (up to 16g/kg/day on the reinstatement of multiple concentrations of ethanol after three cycles of exposure and deprivation), suggesting that the reinforcing properties of ethanol may have been enhanced. The main hypothesis to be tested is that experience with excessive ethanol drinking results in neuroadaptive alterations in the extended amygdala and its interconnections. The rat lines that have been genetically selected for high alcohol drinking at Indiana University (i.e., P, HAD-1 and HAD-2) have been known to exhibit "loss of control" drinking when exposed to the ethanol drinking protocol proposed in this program. The results of this proposal will provide valuable information toward understanding the neural circuitry underlying excessive alcohol drinking and relapse of alcohol drinking. Such information would be important for developing pharmacotherapies for the treatment of alcoholism and alcohol abuse.