Animal Production Core

动物生产核心(APC)将继续提供选择性繁殖的P/NP(偏爱酒精和- 和HAD1-2/LAD1-2(复制高、低度饮酒)大鼠作为研究对象。为了这个 竞争更新，APC还将为研究目的提供选择性培育的复制HAP/LAP CHAP(HAP1×HAP2杂交产生的杂交HAP)。这些 啮齿动物将被提供给由我们的印第安纳ARC支持或附属于我们的印第安纳州ARC和 其他由NIAAA资助的校园内PI，包括R01、U01、F31和我们的T32机构培训 格兰特。P和HAD1-2大鼠是人类酒精中毒的优秀动物模型。P/NP 鼠类，在较小程度上，HAD/LAD和HAP/LAP复制品系的啮齿动物已被广泛 从行为、神经化学、神经药理学和QTL角度描述的。P级大鼠 也构成了研究酗酒的极佳模型，即酒精剥夺效应(ADE， 相当于“故态复萌”的饮酒或“渴求”)和青少年酗酒。此外，P鼠是一种 更好地确定乙醇奖赏作用的神经回路及其相互关系的优秀动物模型 CREB(cAMP反应元件结合)和神经肽Y基因表达对大鼠抗焦虑作用的影响 酒精。具体目标是：1)继续保持我们选择性繁殖的P/NP的核集落 老鼠。2)为校内科研人员选育足够数量的P/NP和HAD1- 2/LAD1-2大鼠。3)继续选择性选育复制HAP/LAP小鼠品系和CHAP小鼠 并生产出足够的动物用于校园研究。4)维持一群N/NIH大鼠( 用于选择选育HAD/LAD和HAS/LAS复制系的基础材料)，因为这 NIH没有保存异质种群，在比较HAD1-2的研究中，它是一个相关的控制线 线与他们的对比LAD1-2线。5)继续协助创造互惠同源品系 从近交系P/NP菌株中筛选，以进一步缩小Chr4对酒精偏好的临界区 QTL的LOD得分为9.2。APC和我们的IARC的成功将在以下方面提供重要进展 了解酒精中毒的遗传决定因素和神经回路。这些科学上的进步 TURN将为治疗酒精中毒的各个方面的药物开发铺平道路。

The Animal Production Core (APC) will continue to supply selectively bred P/NP (alcohol-preferring and - nonpreferring) and HAD1-2/LAD1-2 (replicate high and low alcohol drinking) rats for research. For this competing renewal, the APC will also supply for the purpose of research selectively bred replicate HAP/LAP (high and low alcohol-preferring) and cHAP (crossed HAP produced by HAP1 x HAP2 cross) mice. These rodents will be provided to on-campus investigators supported by or affiliated with our Indiana ARC and other on-campus Pis who are funded by NIAAA with R01s, U01s, F31s, and our T32 Institutional Training Grant. The P and HAD1-2 rats are excellent animal models of the human disorder, alcoholism. The P/NP rats, and to a lesser degree, the HAD/LAD and HAP/LAP replicate lines of rodents have been extensively characterized from behavioral, neurochemical, neuropharmacological, and QTL perspectives. The P rats also constitute an excellent model to study "binge" drinking, the alcohol-deprivation effect (ADE, the equivalent of "relapse" drinking or "craving") and adolescent alcohol abuse. Furthermore, the P rat is an excellent animal model to better define the neurocircuitry of the reward action of ethanol and the relationship of CREB (cAMP-responsive-element binding) and neuropeptide Y gene expression to the anxiolytic effect of alcohol. The Specific Aims are: 1) To continue to maintain our nucleus colonies of selectively bred P/NP rats. 2) To produce for on-campus researchers sufficient number of selectively bred P/NP and HAD1- 2/LAD1-2 rats. 3) To continue to selectively breed the replicate HAP/LAP mouse lines and the cHAP mouse line and to produce sufficient animals for on-campus research. 4) To maintain a colony of N/Nih rats (the foundation stock for the selective breeding of the HAD/LAD and HAS/LAS replicate lines) because this heterogeneous stock is not kept at NIH and it is a relevant control line in studies that compare the HAD1-2 lines with their contrasting LAD1-2 lines. 5) To continue to assist in the creation of reciprocal congenic lines from inbred P/NP strains in order to further narrow the critical region of Chr 4 for alcohol preference in the QTL with a LOD score of 9.2. The success of the APC and our IARC will provide important advances in the understanding of the genetic determinants and neurocircuitry of alcoholism. These scientific advances in turn will pave the way for medication development to treat various aspects of alcoholism.