Effects of Chronic Intranasal Oxytocin

自闭症是一种常见的、损害神经发育的疾病，每88个人中就有一个受到影响。催产素 催产素(OT)，是一种在大脑中产生的激素，储存在脑下垂体后叶，释放到外周。加班 调节密切的选择性社会纽带的形成，并与发现的社会功能障碍有牵连 在自闭症谱系障碍(ASD)中。最近的研究有了巨大的增长，研究了 鼻腔催产素对人类行为的影响，包括建议将其用作各种疾病的治疗方法 包括自闭症在内的精神变态。鼻腔使用催产素治疗自闭症的第二阶段试验正在进行中 12-18岁(ClinicalTrials.gov标识符：NCT01256060)，OT已经经常在 美国给患有自闭症的儿童。OT还在对其他一些疾病进行临床试验，包括 精神分裂症和社交焦虑--因此，人们对其使用的担忧不仅限于它对自闭症的使用。 令人担忧的是，我们最近使用动物模型进行的研究表明，在某些情况下，长期服用OT 剂量可能会对社会纽带产生长期的不利影响。除了对社会行为的影响外，OT 也是调节生殖的关键，并参与生殖行为、精子的产生和 运输、性高潮、分娩和哺乳。 这项建议是对一项已经资助的研究的竞争性修订，该研究旨在研究慢性接触的影响 鼻腔注射OT。这项由基金资助的研究将产生一组非常有价值的猴子，这些猴子长期接受 鼻腔OT或鼻腔生理盐水，这是一个不太可能再创建的队列，而且它将对其进行重新创建 增加额外的结果衡量标准是有利的。最初拨款的目的是审查 慢性鼻腔催产素对社会行为和社会相关神经功能的影响在这次修订中，我们 正在寻求额外的资金来表征这些治疗的长期生殖影响。我们会 研究慢性鼻腔接触催产素对生殖成熟、生殖行为和 生育力、生殖潜力和哺乳期。我们的假设是慢性鼻腔催产素治疗可能会导致 生殖成熟、功能和行为的变化，尤其是男性精子的变化 由于男性生殖道中催产素受体的变化而导致的运输。这些目标没有包含在 原始R01应用程序。这次修订，与最初的赠款一样，是在与一个 在人类身上进行鼻腔OT临床试验的科学家；此外，我们还增加了 生殖生物学。

Autism is a common, impairing neurodevelopmental disorder affecting 1 in 88 individuals. Oxytocin (OT), is a hormone produced in the brain and stored in the posterior pituitary for release into the periphery. 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 an enormous increase in recent research examining the effects of intranasal OT on human behavior, including suggestions for its use as a therapeutic for various psychopathologies including ASD. Phase 2 trials for use of intranasal OT in ASD 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. OT is also in clinical trials for a number of other disorders, including schizophrenia and social anxiety - thus concerns about its usage are not limited to its use for ASD. Alarmingly, our recent research using animal models suggests that chronic administration of OT at some dosages can have long-term, adverse effects on social bonding. In addition to its effects on social behavior, OT is also crucial to the regulation of reproduction, and is involved in reproductive behavior, sperm production and transport, orgasm, birth, and lactation. This proposal is a competitive revision to an already funded study examining the effects of chronic exposure to intranasal OT. The funded study will produce an extremely valuable set of monkeys treated chronically with either intranasal OT or intranasal saline, a cohort which is unlikely ever to be re-created, and to which it would be advantageous to add additional outcome measures. The aims of the original grant are to examine the effects of chronic intranasal OT on social behavior and socially related neural function. With this revision, we are seeking additional funding to characterize the long-term reproductive effects of these treatments. We will examine the role of chronic exposure to intranasal OT on reproductive maturation, reproductive behavior and fertility, reproductive potential, and lactation. Our hypothesis is that chronic intranasal OT treatment may lead to changes in reproductive maturation, function and behavior, and, particularly in males, changes in sperm transport due to alteration in OT receptors in the male reproductive tract. These aims are not covered in the original R01 application. This revision, as with the original grant, is carried out in close collaboration with one of the scientists carrying out a clinical intranasal OT trial in humans; in addition, we have added experts in reproductive biology.