Effects of Chronic Intranasal Oxytocin

慢性鼻内催产素的作用

• 批准号: 8502716
• 负责人: Karen L. Bales
• 金额: $ 52.6万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 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/8502716
• 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

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损害性神经发育障碍，涉及社会互动和社会沟通的缺陷。催产素（OT）是一个9 下丘脑产生并储存在垂体后叶的氨基酸肽。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。最近有大量研究检查鼻内OT对人类行为的影响，包括建议将其用作涉及社交缺陷的各种精神病理学的治疗方法，包括ASD。在12-18岁的儿童中使用鼻内OT治疗自闭症的2期试验正在进行中（Clinicaltrials.gov标识符：NCT 01256060），在美国，OT已经经常被开给ASD儿童。令人担忧的是，我们在动物模型中的初步数据显示，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是负面的。除了我们的初步研究外，还没有在人类或任何动物模型中长期使用鼻内OT的研究;这就是我们在这项研究中所做的。 目前的研究的目的是研究慢性鼻内OT管理的选择性社会行为的动物模型（草原田鼠和titi猴），以及自闭症的社会缺陷的小鼠模型的发展影响。在啮齿动物模型中，给药的剂量、频率和年龄将有所不同。管理的即时社会影响，以及对社会行为，重复行为和焦虑的长期影响将被探讨，以及OT和加压素系统的变化和功能性神经变化对社会刺激的反应。在titi猴子中，我们将使用临床试验中使用的剂量，并检查对社会行为，重复行为和焦虑的短期和长期影响。最后，我们将通过PET成像检查慢性鼻内OT或溶媒治疗的titi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。