The Role of Corticotropin-Releasing Factor in Primate Maternal Behavior

描述(申请人提供)：在女性中，压力和一些与压力相关的精神病理疾病，包括严重的抑郁障碍、产后抑郁和创伤后应激障碍，都可能导致母亲行为受损，并增加虐待儿童的可能性。压力和与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与大脑促肾上腺皮质激素释放因子(CRF)系统的过度活动有关。在啮齿动物中，应激增加了行为相关核团中CRF的表达，并且CRF已被证明扰乱了母亲的行为，并增加了婴儿的杀伤率。此外，大脑中CRF浓度的升高与灵长类动物母亲行为受损有关。这项研究将把绒猴发展成一种新的灵长类模式！研究母亲行为中应激相关缺陷的机制。此外，它还将检验这一假设，即高水平的CRF可以扰乱灵长类动物的母体行为。其具体目的是(1)表征急性应激和CRF-1受体拮抗剂对母体行为的影响，(2)确定侧脑室注射CRF是否抑制母体行为，(3)表征CRF、CRF-1受体和CRF结合蛋白在绒猴脑中的分布，并确定急性应激对这一系统的影响。这些研究将阐明应激、应激相关的精神病理学和灵长类动物母体行为之间的关系，并将为后续研究慢性和急性应激对母体和虐待行为的影响奠定必要的基础。因此，这项工作将对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障碍，可以损害母亲的行为，增加虐待儿童的可能性；然而，机制尚不清楚。这项研究将发展绒猴作为一种新的灵长类动物模型，以了解急性和慢性应激对母体行为的影响，并将开始确定潜在的机制。最终，这项研究将对理解和治疗女性压力相关的精神病理学产生影响。

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.