Core--Primate

埃默里大学精神疾病神经科学中心（CNMD）的灵长类动物模型核心（Core C）将作为个体临床前研究项目使用的所有非人类灵长类动物的来源。具体而言，Core C将产生并表征非人类灵长类动物表观遗传早期生活压力（ELS）模型，该模型涉及恒河猴（Macaca mulatta）母子二代新生儿暴露于低觅食（LFD）或可变觅食（VFD）需求的日常食物定量长达三个月。严格的VF条件的一个直接后果是母亲对婴儿请求接触和关注的反应时间的减少。VF条件允许幼猴正常的社会和身体发育，但显著增加其随后对应激挑战的行为和生理敏感性，包括对去甲肾上腺素能和血清素能焦虑药物的敏感性，以及成年猴CSF中CRF水平的持续增加。这些发现表明，通过VF抚养的ELS产生对压力经验的长期反应性增加，这与人类精神疾病的特征一致。该程序提供了一些重要的优势和有效性来源：(1)范式所施加的偶发是自然的，婴儿的发展受到对母亲可获得性的生态需求的影响；(2)这种需求是在婴儿行为发展的关键时期施加的，此时婴儿开始探索环境，通常会寻求安慰；(3)在一些人类精神病理学中发现，缺陷反映在猴子成年后对压力经历的反应能力上。将这种灵长类动物模型与遗传模型和ELS啮齿动物模型（见核心B）进行比较，将允许个别中心研究项目验证这一论点，即在不同物种中，相似的神经回路和细胞内机制受到遗传和表观遗传因素的影响，从而导致类抑郁综合征。此外，各种治疗方法（抗抑郁药，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该模型中进行测试。为此，Core C将描述每只动物的行为和HPA轴应激反应，并为各个中心研究项目提供采样服务、CNS引导插管植入等手术服务、慢性药物治疗和尸检。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。

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.