Core--Rat

核心--老鼠

• 批准号: 6324765
• 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 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6324765
• 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.

埃默里大学 Silvio O. Conte 精神障碍神经科学 (CCNMD) 中心的大鼠模型核心（核心 B）是整个中心的一个组成部分。核心 B 将作为各个临床前研究项目使用的所有啮齿动物的来源。具体来说，Core B 将产生并表征与抑郁样综合征的易感性相关的大鼠表观遗传早期生命应激 (ELS) 模型。核心 B 人员将饲养啮齿动物，提供高质量的动物护理和统一应用生成 ELS 模型所需的新生儿操作方案，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，从出生后 (PND) 2-14 天开始暴露于不同的饲养条件，包括：(1) 动物设施饲养 (AFR) 群体对照，(2) 短暂处理加 15 分钟母体分离 (HMS 15) 处理对照，(3) 短暂处理加 180 分钟母体分离 (HMS 180)。所有单独的研究项目都将评估这些动物的性别特定影响。对本 CCNMD 的各个基础研究项目中从这些标准化饲养条件获得的数据进行比较，将能够识别受早期生活压力影响并引起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，回归模型可用于阐明这些中枢神经系统系统之间在这种情况的发生过程中的相互作用。此外，将在这些模型中测试各种治疗方法（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功效。为此，核心 B 将表征每只动物的行为和 HPA 轴应激反应性，提供快感缺乏、焦虑恐惧样行为的表型筛查，并提供外科服务，如慢性颈静脉导管插入术、中枢神经系统引导插管植入、Alzet 微型泵准备和植入、居民入侵者社交失败暴露以及研究项目要求的其他方案。核心 B 将提供特征化的大鼠，或将 HMS 大鼠的脑组织、其他组织（肾上腺、垂体等）、血液或脑脊液提供给各个研究项目。该组织的优势在于保持动物处理和所有方案实施的一致性，以便每个临床前研究项目都能接收具有相同特征和处理方式的动物进行研究。