Core--Rat

核心--老鼠

• 批准号: 6259208
• 负责人: PAUL M PLOTSKY
• 金额: $ 23.19万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6259208
• 关键词: animal care; behavioral /social science research tag; biomedical facility; clinical depression; disease /disorder model; early experience; gender difference; hypothalamic pituitary adrenal axis; laboratory rat; mother deprivation

The Rat Model Core (Core B) of the Emory University Silvio O. Conte Center~f6r the Neuroscience of Mental Disorders (CCNMD) represents an integral component of the overall Center. Core B will serve as the source of all rodents used by the individual preclinical Research Projects. In specific, Core B will produce and characterize a rat epigenetic early life stress (ELS) model associated with vulnerability to the development of a depression-like syndrome. Core B personnel will breed rodents, provide high quality animal care and uniformly applied neonatal manipulation protocols necessary to generate the ELS model, characterize the phenotype of all animals, ascertain the stage of the estrus cycle in adult female animals, and provide experimental manipulations as required by individual preclinical Research Projects within the Center. This epigenetic ELS model consists of Long Evans rats which are exposed to different rearing conditions from postnatal days (PND) 2-14, including: (1) animal facility reared (AFR) colony controls, (2) brief handling plus 15 min maternal separation (HMS 15) handling controls, (3) brief handling plus 180 min maternal separation (HMS 180). All individual Research projects will assess these animals for gender specific effects. Comparison of data obtained from these standardized rearing conditions among the various basic Research projects of this CCNMD will permit identification of central neurocircuit and intracellular mechanisms which are impacted by early life stress and which give rise to depressive-like syndrome; furthermore, since the animal models will be standardized, regression modeling can be used to elucidate interactions among these CNS systems in the genesis of this condition. Furthermore, the efficacy of various treatments (antidepressant, antisense, corticotropin releasing factor antagonist) in reversing aspects of depressive-like syndrome will be tested in these models. To this end, Core B will characterize the behavioral and HPA axis stress responsiveness of each animal, provide phenotypic screening for anhedonia, anxiety4fear-like behavior, as well as pr6viding surgical services such as chronic jugular catheterization, CNS guide cannula implantation, Alzet minipump preparation and implantation, resident intruder social defeat exposure, and other protocols as required by the Research Projects. Core B will provide characterized rats or will provide brain tissue, other tissue (adrenal, pituitary, etc), blood, or CSF from the HMS rats to the individual Research Projects. This organization has the advantage of maintaining consistency in animal handling and implementation of all protocols so that each preclinical Research Project receives identically characterized and treated animals for study.

Emory大学Silvio O. Conte中心的大鼠模型核心（Core B）是精神障碍神经科学（CCNMD）的一个组成部分。核心B将作为单个临床前研究项目使用的所有啮齿动物的来源。具体而言，Core B将产生并表征与抑郁样综合征易感性相关的大鼠表观遗传早期生活应激（ELS）模型。核心B人员将繁殖啮齿动物，提供高质量的动物护理，统一应用生成ELS模型所需的新生儿操作协议，表征所有动物的表型，确定成年雌性动物的发情周期阶段，并根据中心内各个临床前研究项目的要求提供实验操作。该表观遗传ELS模型由Long Evans大鼠组成，这些大鼠在出生后2-14天（PND）暴露于不同的饲养条件下，包括：(1)动物设施饲养（AFR）群体对照，(2)短暂处理加15分钟母分离（HMS 15）处理对照，(3)短暂处理加180分钟母分离（HMS 180）。所有单独的研究项目都将评估这些动物的性别特异性影响。在CCNMD的各种基础研究项目中，从这些标准化饲养条件中获得的数据进行比较，将允许识别受早期生活压力影响并导致抑郁样综合征的中枢神经回路和细胞内机制；此外，由于动物模型将被标准化，回归模型可以用来阐明这些中枢神经系统之间的相互作用在这种情况的起源。此外，各种治疗方法（抗抑郁药、反义药、促肾上腺皮质激素释放因子拮抗剂）在逆转抑郁样综合征方面的疗效将在这些模型中进行测试。为此，Core B将描述每只动物的行为和HPA轴应激反应，提供快感缺乏、焦虑恐惧样行为的表型筛选，并根据研究项目要求提供慢性颈静脉导管置管、中枢神经系统引导套管植入、Alzet微型泵制备和植入、居民入侵者社会失败暴露等手术服务。核心B将提供特征大鼠或提供HMS大鼠的脑组织、其他组织（肾上腺、垂体等）、血液或脑脊液给各个研究项目。该组织的优势在于保持动物处理和执行所有协议的一致性，以便每个临床前研究项目接收相同特征和处理的动物进行研究。