The Role of Corticotropin-Releasing Factor in Primate Maternal Behavior

促肾上腺皮质激素释放因子在灵长类动物母性行为中的作用

• 批准号: 7267990
• 负责人: WENDY SALTZMAN
• 金额: $ 21.51万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7267990
• 关键词: Acute; Anxiety; Anxiety Disorders; Behavior; Behavioral; Biology; Brain; Brain region; Callithrix; Callithrix jacchus jacchus; Cell Nucleus; Child; Child Abuse; Chronic; Chronic stress; Clinical; Condition; Corticotropin Receptors; Corticotropin-Releasing Hormone; Cues; Dependence; Development; Endocrine; Female; Foundations; Future; Grant; Human; Hyperactive behavior; Infant; Infusion procedures; Lead; Major Depressive Disorder; Maternal Behavior; Mediating; Modeling; Monkeys; Moods; Neurobiology; Neurons; Numbers; Pliability; Post-Traumatic Stress Disorders; Postpartum Depression; Primates; Psychopathology; Rate; Research; Research Personnel; Rodent; Role; Sensory; Stress; Structure of terminal stria nuclei of preoptic region; System; Testing; Woman; Work; acute stress; base; corticotropin releasing factor-binding protein; killings; neurochemistry; neuromechanism; nonhuman primate; novel; paraventricular nucleus; programs; pup; receptor; research study

DESCRIPTION (provided by applicant): In women, both stress and a number of stress-related psychopathological conditions, including major depressive disorder, postpartum depression, and post-traumatic stress disorder, can lead to impaired maternal behavior and increased likelihood of child abuse. The mechanisms by which stress and stress- related psychopathology disrupt maternal behavior are not known. Both stress and stress-related psychopathology, however, are commonly associated with hyperactivity of the brain's corticotropin-releasing factor (CRF) systems. In rodents, stress increases expression of CRF in behaviorally relevant nuclei, and CRF has been shown to disrupt maternal behavior and increase rates of infant-killing. Moreover, elevated CRF concentrations in the brain correlate with impaired maternal behavior in primates. This research will develop the marmoset monkey as a novel primate mode! in which to investigate the mechanisms of stress- related deficits in maternal behavior. In addition, it will test the hypothesis that high levels of CRF can disrupt maternal behavior in primates. The specific aims are to (1) characterize the effects of acute stress and a CRF type-1 receptor antagonist on maternal behavior, (2) determine whether intracerebroventricular administration of CRF inhibits maternal behavior, and (3) characterize the distribution of CRF, CRF type-1 receptor, and CRF-binding protein in the marmoset brain, and determine the effects of acute stress on this system. These studies will elucidate the relationships among stress, stress-related psychopathology, and maternal behavior in primates and will lay the essential foundations for subsequent studies of the effects of both chronic and acute stress on maternal and abusive behavior. Thus, this work will make a significant contribution to our understanding of the neurobiology of maternal behavior in primates, including humans. Relevance: Stress, as well as stress-related mood and anxiety disorders, can impair maternal behavior and increase the likelihood of child abuse; however, the mechanisms are not known. This research will develop the marmoset as a new primate model for understanding the effects of acute and chronic stress on maternal behavior and will begin to identify the underlying mechanisms. Ultimately, this research will have implications for the understanding and treatment of stress-related psychopathology in women.

描述（由申请人提供）：在女性中，压力和许多与压力相关的精神病理状况，包括重度抑郁症、产后抑郁症和创伤后应激障碍，都可能导致母亲行为受损并增加虐待儿童的可能性。压力和压力相关的精神病理学破坏母亲行为的机制尚不清楚。然而，压力和与压力相关的精神病理学通常都与大脑促肾上腺皮质激素释放因子（CRF）系统的过度活跃有关。在啮齿动物中，压力会增加行为相关细胞核中 CRF 的表达，并且 CRF 已被证明会扰乱母性行为并增加婴儿死亡率。此外，大脑中 CRF 浓度升高与灵长类动物母性行为受损相关。这项研究将把狨猴发展为一种新颖的灵长类动物模式！其中调查母亲行为中与压力相关的缺陷的机制。此外，它将检验以下假设：高水平的 CRF 会扰乱灵长类动物的母性行为。具体目标是 (1) 表征急性应激和 CRF 1 型受体拮抗剂对母体行为的影响，(2) 确定脑室内给予 CRF 是否会抑制母体行为，以及 (3) 表征 CRF、CRF 的分布狨猴大脑中的 1 型受体和 CRF 结合蛋白，并确定急性应激对该系统的影响。这些研究将阐明灵长类动物的压力、压力相关的精神病理学和母性行为之间的关系，并将为后续研究慢性和急性压力对母性和虐待行为的影响奠定重要基础。因此，这项工作将为我们理解包括人类在内的灵长类动物母性行为的神经生物学做出重大贡献。相关性：压力以及与压力相关的情绪和焦虑症会损害母亲的行为并增加虐待儿童的可能性；然而，其机制尚不清楚。这项研究将把狨猴开发为一种新的灵长类动物模型，用于了解急性和慢性压力对母性行为的影响，并将开始确定潜在的机制。最终，这项研究将对女性压力相关精神病理学的理解和治疗产生影响。