Effects of Chronic Intranasal Oxytocin

慢性鼻内催产素的作用

基本信息

批准号：
8676843
负责人：
Karen L. Bales
金额：
$ 110.39万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-05 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8676843
关键词：
18 year old Adolescent Affect Age Amino Acids Animal Experimentation Animal Model Animals Anxiety Area Autistic Disorder BTBR Mouse Behavior Brain Cerebrum Chicago Child Chronic Clinical Trials Data Development Dose Emotional Empathy Exposure to Frequencies Functional disorder Goals Human Hypothalamic structure Illinois Individual Institutes Intranasal Administration Knowledge Long-Term Effects Longitudinal Studies Macaca mulatta Mammals Measures Methods Microtus Modeling Monkeys Mus Neurodevelopmental Disorder Neuropeptides Neurophysiology - biologic function Oxytocin Oxytocin Receptor Patients Peptides Phase II Clinical Trials Pilot Projects Positron-Emission Tomography Posterior Pituitary Gland Primates Process Production Psychopathology Rattus Research Research Personnel Rodent Rodent Model Social Behavior Social Interaction Stimulus Suggestion System Testing Therapeutic Trust United States Universities Vasopressin Receptor Vasopressins autism spectrum disorder base behavior change clinical practice dosage glucose metabolism glucose uptake mouse model nonhuman primate novel patient population prairie vole relating to nervous system research study response social social attachment social communication

项目摘要

DESCRIPTION (provided by applicant): Autism is a common, impairing neurodevelopmental disorder involving deficits in social interaction and social communication. Oxytocin (OT) is a nine amino acid peptide produced in the hypothalamus and stored in the posterior pituitary. OT regulates the formation of close selective social bonds and has been implicated in the social dysfunction found in autism spectrum disorders (ASD). There has been a proliferation of recent research examining the effects of intranasal OT on human behavior, including suggestions for its use as a therapeutic for various psychopathologies involving social deficits, including ASD. Phase 2 trials for use of intranasal OT in autism are underway for children 12-18 years of age (Clinicaltrials.gov identifier: NCT01256060), and OT is already frequently prescribed in the United States to children with ASD. Alarmingly, our preliminary data in animal models show that while administration of intranasal OT has positive effects of social behavior in the short-term, long-term effects at some dosages are negative. Aside from our pilot study, there have been no long-term studies of chronic intranasal OT use in humans or in ANY animal model; that is what we propose to do in this study. The aim of the current study is to examine the developmental effects of chronic intranasal OT administered to two animal models of selective social behavior (prairie voles and titi monkeys), as well as one mouse model of the social deficits of autism. In the rodent models, dosage, frequency, and age of administration will be varied. The immediate social effects of administration, as well as long-term effects on social behavior, repetitive behavior, and anxiety will be explored, as well as changes to the OT and vasopressin systems and functional neural changes in response to social stimuli. In titi monkeys, we will administer the dosage being used in clinical trials and examine the short-term and long-term effects on social behavior, repetitive behavior, and anxiety. Finally, we will examine changes to local cerebral glucose metabolism in titi monkeys treated with chronic intranasal OT or vehicle via PET imaging, with a focus on areas that produce or have receptors for OT.

描述（由申请人提供）：自闭症是一种常见的神经发育障碍，涉及社交互动和社交沟通缺陷。催产素 (OT) 是九氨基酸肽在下丘脑中产生并储存在垂体后叶中。 OT 调节紧密选择性社会纽带的形成，并与自闭症谱系障碍 (ASD) 中发现的社会功能障碍有关。最近有大量研究探讨鼻内 OT 对人类行为的影响，包括建议将其用作涉及社交缺陷（包括自闭症谱系障碍）的各种精神病理学的治疗方法。针对 12-18 岁儿童的鼻内 OT 治疗自闭症的 2 期试验正在进行中（Clinicaltrials.gov 标识符：NCT01256060），在美国，OT 已经经常用于 ASD 儿童。令人震惊的是，我们在动物模型中的初步数据表明，虽然鼻内 OT 给药在短期内对社会行为有积极影响，但某些剂量的长期影响却是负面的。除了我们的试点研究之外，还没有对人类或任何动物模型进行慢性鼻内 OT 使用的长期研究；这就是我们在这项研究中建议要做的事情。本研究的目的是检查慢性鼻内 OT 对两种选择性社会行为动物模型（草原田鼠和蒂蒂猴）以及一种自闭症社交缺陷小鼠模型的发育影响。在啮齿动物模型中，给药剂量、频率和年龄会有所不同。将探讨给药的直接社会影响，以及对社会行为、重复行为和焦虑的长期影响，以及对 OT 和加压素系统的变化以及响应社会刺激的功能性神经变化。在蒂蒂猴中，我们将使用临床试验中使用的剂量，并检查其对社交行为、重复行为和焦虑的短期和长期影响。最后，我们将通过 PET 成像检查接受慢性鼻内 OT 或载体治疗的蒂蒂猴局部脑葡萄糖代谢的变化，重点关注产生或具有 OT 受体的区域。