Core 1: Administrative

对人类和动物模型的研究表明，对乙醇的急性行为反应具有预测性。 长期饮酒行为的风险值。在啮齿动物模型中，运动激活和 抗焦虑样活性是两种广泛记载的对乙醇的急性行为反应。压力焦虑 乙醇或乙醇戒断对焦虑的影响已被认为是焦虑的重要因素。 酗酒和累犯的起源。我们实验室最近的结果已经确定了显著的定量 使用焦虑的亮-暗盒转换模型对急性乙醇抗焦虑样活性的性状位点（QTL）进行分析 在33个BXD重组近交系小鼠品系中。同时，我们已经生成了微阵列数据集， 从相同的生理盐水或急性乙醇处理的BXD线，前额叶皮层和核。 最近的研究表明，结合基因表达和行为的QTL分析可以改善 行为QTL候选基因的鉴定。这样的“表达遗传学”有能力识别 高度相关的基因表达模式的网络。将基因表达网络与 行为QTL可以为这种表达网络的功能相关性提供证据， 复杂性状的潜在机制这个发展项目将进一步利用电力 VCU-ARC的整体实验设计，以优先考虑与急性 小鼠的乙醇行为反应。我们将：1）完成腹侧被盖区的微阵列研究 在33个BXD Rl系+/-乙醇（1.8g/kg X 4小时）中; 2）鉴定与以下相关的基因表达网络： 急性乙醇对自发活动和焦虑样行为影响的行为测量;和3）通过 潜在的跨物种比较（项目2，3和试点1）和生物信息学优先级（核心2）， PCR验证的表达变化，我们将选择有限数量的候选者进行直接验证研究 对小鼠后者将使用现有的无效突变小鼠系或用以下药物治疗的动物的行为测试： 病毒载体基因递送。我们希望这能为与基因相关的基因网络提供一种新的验证。 对酒精的急性行为反应此外，我们的小鼠基因靶向和行为测定将 为本中心项目2、3和试点1的研究提供资源。我们共同期待一种新的协同效应 这些关于基因网络对急性乙醇反应的跨物种研究。

Studies in both humans and animal models show that acute behavioral responses to ethanol have predictive value regarding risk for long term ethanol drinking behavior. In rodent models, locomotor activation and anxiolytic-like activity are two widely documented acute behavioral responses to ethanol. Stress, anxiety and effects of ethanol or ethanol-withdrawal on anxiety have been proposed as important factors in the genesis of alcoholism and recidivism. Recent results in our laboratory have identified significant quantitative trait loci (QTLs) for acute ethanol anxiolytic-like activity using the light-dark box transition model of anxiety across 33 BXD recombinant inbred mouse strains. Simultaneously, we have generated microarray datasets from the same saline or acute ethanol-treated BXD lines, for prefrontal cortex and nucleus accumbens. Recent studies suggest that combining QTL analysis of gene expression and behavioral can improve identification of candidate genes for behavioral QTLs. Such "expression genetics" has the power to identify networks of highly correlated gene expression patterns. Correlating genetic expression networks with behavioral QTLs could provide evidence for the functional relevance of such expression networks and candidate mechanisms underlying complex traits. This developmental project will furthermore use the power of the overall experimental design of the VCU-ARC to prioritize gene expression networks linked to acute ethanol behavioral responses in mice. We will: 1) Complete microarray studies for ventral tegmental area across 33 BXD Rl lines +/- ethanol (1.8 g/kg x 4 hours); 2) Identify gene expression networks correlated with behavioral measures of acute ethanol effects on locomotor activity and anxiety-like behavior; and 3) Through potential cross-species comparison (Projects 2, 3 and Pilot 1) and bioinformatics prioritization (Core 2) of PCR-verified expression changes, we will select a limited number of candidates for direct verification studies in mice. The latter will use behavioral testing of existing null mutation mouse lines or animals treated with viral-vector gene delivery. We expect this to provide a novel validation of gene networks correlated with the acute behavioral responses to ethanol. Furthermore, our mouse gene targeting and behavioral assays will provide resources for studies in Projects 2,3 and Pilot 1 of this Center. Together we expect a novel synergy of these cross-species studies on gene networks responding to acute ethanol.