Core--Primate

Emory University Center for Neuroscience of Mental Disorders（CNMD）的灵长类动物模型核心（Core C）将作为单个临床前研究项目使用的所有非人灵长类动物的来源。具体而言，核心C将产生和表征非人灵长类动物表观遗传早期生活应激（ELS）模型，该模型涉及恒河猴（Macaca mulatta）母婴二对体的新生儿暴露于低觅食（LFD）或可变觅食（VFD）需求，以获得长达三个月的每日食物配给。严格的VF条件的直接后果是母亲对婴儿接触和注意的请求做出反应的时间减少。VF条件允许婴儿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去甲肾上腺素能致焦虑药物的敏感性以及成年猴CSF中CRF水平的持续增加。这些研究结果表明，ELS通过VF饲养产生长期增加的反应性，压力的经验，这是符合人类精神疾病的特点。这一程序提供了一些重要的优势和有效性来源：（1）由范式强加的偶然性是自然主义的，婴儿发展受到对母亲可用性的生态需求的影响，（2）这些需求是在婴儿行为发展的关键时期强加的，当婴儿开始探索他们的环境时，他们通常会寻求安慰，（3）正如在一些人类精神病理学中发现的那样，缺陷反映在猴子成年后对压力经历的反应能力上。将该灵长类动物模型与遗传和ELS啮齿类动物模型（见核心B）进行比较，将允许各个中心研究项目检验以下论点：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，从而引起抑郁样综合征。此外，将在该模型中检测各种治疗（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。 为此，核心C将表征每只动物的行为和HPA轴应激反应，并为各个中心研究项目提供采样服务、手术服务（如CNS引导套管植入）、慢性药物治疗和尸检。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接收相同表征和治疗的动物进行研究。

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.