Core--Rat

核心--老鼠

• 批准号: 6341049
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6341049
• 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 Center的大鼠模型核心（Core B）〜F6R精神疾病的神经科学（CCNMD）代表了整个中心的组成部分。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。在特定的情况下，核心B将产生和表征与与抑郁症状综合征发展的脆弱性相关的大鼠表观遗传早期生命应力（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以及统一应用的新生儿操纵方案，以生成ELS模型，表征所有动物的表型，确定成年雌性动物的发情阶段，并提供该中心中各个临时研究项目所需的实验性操纵。 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).所有个别研究项目都将评估这些动物的性别特定效果。从这些标准化饲养条件中获得的数据比较该CCNMD的各种基础研究项目将允许识别受到早期生活压力的影响，并引起抑郁样综合征。此外，由于动物模型将是标准化的，因此可以使用回归模型来阐明在这种情况的起源中这些CNS系统之间的相互作用。此外，在这些模型中，将测试各种治疗方法（抗抑郁药，反义，皮质激素释放因子拮抗剂）的功效。 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.核心B将提供特征性的大鼠，或者将提供从HMS大鼠到单个研究项目的脑组织，其他组织（肾上腺，垂体等），血液或CSF。该组织具有保持动物处理和实施所有方案的一致性的优势，因此每个临床前研究项目都具有相同的表征和治疗的动物进行研究。