Core--Rat

埃默里大学西尔维奥·孔特中心的大鼠模型核心(B核心)精神疾病神经科学(CCNMD)是整个中心不可或缺的组成部分。核心B将作为个人临床前研究项目使用的所有啮齿动物的来源。具体地说，核心B将产生并表征一种与抑郁症样综合征的易感性相关的大鼠表观遗传早期生活应激(ELS)模型。核心B人员将饲养啮齿动物，提供高质量的动物护理和统一应用的新生儿操作规程，以生成ELS模型，确定所有动物的表型，确定成年雌性动物的发情周期阶段，并根据中心内个别临床前研究项目的要求提供实验操作。这种表观遗传学ELS模型由Long Evans大鼠组成，它们从出生后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+母体分离15分钟(HMS 15)处理对照，(3)短暂处理+母体分离180分钟(HMS 180)。所有单独的研究项目都将评估这些动物的性别影响。将这些标准化饲养条件下的数据在CCNMD的不同基础研究项目中进行比较，将有助于识别受早期生活应激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种情况发生时这些中枢神经系统之间的相互作用。此外，将在这些模型中测试各种治疗方法(抗抑郁剂、反义药物、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有效性。为此，Core B将表征每只动物的行为和HPA轴的应激反应，为快感缺乏、焦虑和恐惧样行为提供表型筛选，以及提供外科服务，如慢性颈静脉插管、中枢神经系统引导管植入、阿尔茨海默特微型泵的准备和植入、住院入侵者社会挫败暴露，以及研究项目所需的其他方案。核心B将向个别研究项目提供HMS大鼠的脑组织、其他组织(肾上腺、垂体等)、血液或脑脊液。该组织的优势是在动物处理和所有方案的实施上保持一致性，以便每个临床前研究项目接收相同的特征和治疗的动物进行研究。

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.