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。 在延伸的杏仁核及其相互联系中 大鼠的酒精摄入量。一系列实验将确保 过量乙醇灌胃大鼠的质量控制和可利用度 饮酒动物模型。为此，高饮酒率的P和HAD (两个复制系)大鼠将通过酒精饮酒方案进行饲养 涉及重复暴露于多种乙醇浓度的循环 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细化酒精饮酒方案 改变初始和后续乙醇长度的影响 暴露和2)剥夺和改变可用的乙醇 浓度。第三系列实验将检验这一影响。 乙醇的可获得性和匮乏循环的实验范式在 低度饮酒模式(如NP、LAD-1、LAD-2和 Wistar)大鼠。酒精饮酒协议导致非常高水平的 P和HAD大鼠酒精摄入量(恢复后高达16g/kg/d) 三次接触后的多个浓度的乙醇和 剥夺)，这表明乙醇的增强特性可能具有 得到了增强。需要检验的主要假设是， 过量饮酒导致大鼠神经适应性改变 延伸的杏仁核及其相互连接。一直以来的老鼠线 在印第安纳大学被基因选择为高酒精饮酒者(即P， 众所周知，HAD-1和HAD-2)在饮酒时表现出“失控” 接触到本计划中提出的酒精饮酒方案。这个 该提案的结果将为以下方面提供有价值的信息 了解酗酒和过度饮酒背后的神经回路 酗酒复发。这样的信息对于 发展治疗酒精中毒和酒精中毒的药物疗法 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.