Core--Primate

核心——灵长类

• 批准号: 6324766
• 负责人: Thomas R. Insel
• 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/6324766
• 关键词: Macaca mulatta; animal care; animal developmental psychology; behavioral /social science research tag; biomedical facility; coping; disease /disorder model; early experience; hypothalamic pituitary adrenal axis; mental disorders; mother child interaction

The Primate Animal Model Core (Core C) of the Emory University Center for Neuroscience of Mental Disorders (CNMD) will serve as the source of all non-human primates used by the individual preclinical Research Projects. In specific, Core C will produce and characterize a non-human primate epigenetic early life stress (ELS) model involving neonatal exposure of rhesus monkeys (Macaca mulatta) mother-infant dyads to low foraging (LFD) or variable foraging (VFD) demand for their daily food ration up for to three months. An immediate consequence of the stringent VF condition is a reduction in the amount of time mothers respond to infant solicitations for contact and attention. The VF condition permits normal social and physical development of infant monkeys but significantly increases their subsequent behavioral and physiological sensitivity to stressful challenges including sensitivity to noradrenergic and serotonergic anxiogenic drugs and persistent increases in CSF levels of CRF in adult monkeys. These findings indicate that ELS via VF rearing produces long-term increases in reactivity to stressful experience which are consistent with features of human psychiatric disorders. This procedure offers some important advantages and sources of validity: (l) the contingencies imposed by the paradigm are naturalistic, infant development is influenced by ecological demands on mother's availability, (2) the demands are imposed during a critical period of infant, behavioral development when infants normally solicit reassurance as they begin to explore their environment, (3) as found in some human psychopathologies, deficits are reflected in the capacity of monkeys to respond to stressful experiences as adults. Comparison of this primate model with the genetic and ELS rodent models (see Core B) will permit individual Center Research Projects to test the thesis that, in diverse species, similar neurocircuits and intracellular mechanisms are impacted by genetic and epigenetic factors across which give rise to depressive-like syndrome. Furthermore, the efficacy of various treatments (antidepressant, corticotropin releasing factor antagonist) in reversing aspects of depressive-like syndrome will be tested in this model. To this end, Core C will characterize the behavioral and HPA axis stress responsiveness of each animal as well as providing sampling services, surgical services such as CNS guide cannula implantation, chronic drug treatments, and necropsy to the individual Center 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.

埃默里大学神经科学中心（CNMD）的灵长类动物模型核心（核心C）将作为各个临床前研究项目使用的所有非人类灵长类动物的来源。在具体而言，核心C将产生和表征非人类灵长类动物表观遗传早期生活压力（ELS）模型，涉及恒河猴的新生儿暴露（Macaca Mulatta）母亲对二元组对低觅食（LFD）或对变量（VFD）的需求（VFD）的需求（VFD）他们的日常食品定量长达三个月。严格的VF条件的直接后果是，母亲对婴儿的接触和关注征求的反应减少了。 VF条件允许婴儿猴子的正常社会和身体发展，但显着提高了其随后对压力挑战的行为和生理敏感性，包括对成年猴子CRF水平的敏感性和血清素能药物的敏感性以及持续的增加。这些发现表明，通过VF饲养的EL会导致对压力体验的反应性长期增加，这与人类精神疾病的特征一致。该程序提供了一些重要的有效性和有效性的来源：（l）范式施加的意外事件是自然主义的，婴儿的发育受到母亲可用性的生态需求的影响，（2）在婴儿的关键时期，行为发展的关键时期施加了需求当婴儿在开始探索环境时通常会征求保证时，（3）在某些人类的心理病理学中发现，赤字会反映在猴子的能力下，以应对成年人的压力经历。将这种灵长类动物模型与遗传和ELS啮齿动物模型（请参见核心B）进行比较，将允许单个中心研究项目测试以下论点：在不同的物种中，相似的神经环节和细胞内机制受到遗传和表观遗传因素的影响，这些因素会导致其引起抑郁症综合征。此外，将在该模型中测试各种治疗（抗抑郁药，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。 为此，Core C将表征每种动物的行为和HPA轴应激反应性以及提供采样服务，CNS等手术服务（例如指导套管植入，长期药物治疗和尸检）为个别中心研究项目。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。