Effects of Chronic Intranasal Oxytocin

慢性鼻内催产素的作用

• 批准号: 8400995
• 负责人: Karen L. Bales
• 金额: $ 56.85万
• 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/8400995
• 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. PUBLIC HEALTH RELEVANCE: Autism is a common, impairing neurodevelopmental disorder affecting 1 in 110 individuals. This proposal will investigate the long-term effects of chronic intranasal oxytocin, which has been proposed as a treatment for autism, in animal models.

描述（由申请人提供）：自闭症是一种常见的、损害性的神经发育障碍，涉及社会互动和社会沟通的缺陷。催产素（OT）是9