Core--Primate

核心——灵长类

• 批准号: 6259209
• 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 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6259209
• 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.

埃默里大学精神疾病神经科学中心(CNMD)的灵长类动物模型核心(C核心)将作为个人临床前研究项目使用的所有非人类灵长类动物的来源。具体地说，Core C将产生并表征一个非人类灵长类表观遗传早期生活应激(ELS)模型，该模型涉及恒河猴(Macaca Mulatta)母婴二元组在长达三个月的每日食物配给的低觅食(LFD)或可变觅食(VFD)需求下的暴露。严格的VF条件的直接后果是母亲对婴儿接触和关注的请求做出反应的时间减少。VF条件允许幼猴正常的社会和身体发育，但显著增加了它们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和5-羟色胺能抗焦虑药物的敏感性，以及成年猴子脑脊液中CRF水平的持续增加。这些发现表明，通过室颤饲养产生的ELS对应激经历的反应性长期增加，这与人类精神障碍的特征一致。这一程序提供了一些重要的优势和有效性来源：(L)该范式强加的偶然性是自然主义的，婴儿的发展受到对母亲可获得性的生态需求的影响，(2)这些需求是在婴儿的关键时期强加的，当婴儿开始探索他们的环境时，行为发育通常会寻求安慰，(3)正如在一些人类精神病理学中发现的那样，缺陷反映在猴子作为成年人对应激经历的反应能力上。将这一灵长类动物模型与遗传和ELS啮齿动物模型(见核心B)进行比较，将使各个中心研究项目能够检验这一论点，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，从而导致抑郁样综合症。此外，各种治疗方法(抗抑郁剂、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将在该模型中进行测试。为此，Core 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、外科服务(如中枢神经系统导管植入)、慢性药物治疗和尸检。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。