Oxytocin as a therapeutic target for Schizophrenia

催产素作为精神分裂症的治疗靶点

• 批准号: 8888359
• 负责人: DAVID FEIFEL
• 金额: $ 38.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8888359
• 关键词: Acute; Address; Advanced Development; Adverse effects; Affinity; Anhedonia; Animal Experimentation; Animal Experiments; Animal Model; Animal Testing; Animals; Antipsychotic Agents; Attention; Biological; Biological Markers; Brain; Brain region; Characteristics; Chronic; Clinical; Clinical Treatment; Cognition; Cognitive; Cognitive deficits; Data; Development; Disease; Dose; Evaluation; Exhibits; Female; Future; Hormones; Human; Individual; Investigation; Knowledge; Literature; Long-Term Effects; Measurement; Mediating; Mental disorders; Modeling; Nature; Oxytocin; Patients; Performance; Peripheral; Pharmaceutical Preparations; Phenotype; Process; Property; Publishing; Randomized Controlled Trials; Rattus; Rattus norvegicus; Receptor Activation; Regimen; Research; Resistance; Rodent; Route; Safety; Schizophrenia; Sex Characteristics; Short-Term Memory; Site; Symptoms; Syndrome; System; Testing; Text; Therapeutic; Therapeutic Effect; Time; Vasopressin Receptor; Withdrawal; base; clinical effect; cognitive neuroscience; design; drug candidate; improved; male; neurobiological mechanism; neuromechanism; novel; novel strategies; pre-clinical; public health relevance; reproductive function; reproductive hormone; research study; sex; social; social cognition; therapeutic target; tool; treatment duration; visual memory

 DESCRIPTION (provided by applicant): There is a tremendous need for improved treatments for schizophrenia (SCZ), especially for its 'negative' symptoms and cognitive deficits. Oxytocin is a reproductive hormone that is also a powerful regulator of brain processes that are very relevant to SCZ. Preliminary research in animals and humans indicate that the oxytocin system may be an auspicious target for developing new SCZ treatments. However, in order for that to occur, a much greater understanding of oxytocin's potential anti-SCZ effects is urgently needed to address inconsistencies and gaps in the existing body of data. Animal studies are an important tool for obtaining information about potential new treatments, but there has been surprisingly little animal research into oxytocin's anti-SCZ potential. The overall aim of this project is to address this critical gap in knowledge. Since it is unclear which specific features f SCZ may be benefited by oxytocin, several experiments have been thoughtfully designed to evaluate its effects in a battery of state-of-the-art animal tests developed to represent the distinct clinical features of SCZ's cognitive and negative symptoms. Other experiments are designed to uncover the biological mechanisms and brain circuits that underlie oxytocin's anti-SCZ effects, something that has not previously been well studied. By testing the effects of long-term oxytocin treatment via the intranasal route, the standard route in human studies, these experiments will provide an understanding of oxytocin's effects that is more relevant to the chronic nature of clinical treatment than the preponderance of previous animal studies on this topic, which have typically examined one-time, peripheral or central oxytocin administration. As it is highly involved in reproductive function, oxytocin's brain effects are likely to differ in maes and females, but animal experiments investigating its SCZ-relevant effects have almost exclusively included only male subjects. By incorporating both female and male animals in experiments, this project will provide much needed information about possible sex differences in oxytocin's anti-SCZ effects. Another important feature of this project is that it will advance the characterization of a promising rat model of relevance to SCZ and facilitate the ultimate assessment of the validity of the tests used to model features of SCZ. This project will greatly expand the current body of scientific knowledge regarding oxytocin's anti-SCZ properties, including important information regarding potential dose-, sex-, and time-dependent aspects of its clinical effects, potential adverse effects, as well as individual characteristics that may hel identify likely responders to oxytocin treatment. These findings will guide future studies in animals and in patients with SCZ, while the findings regarding oxytocin's neurobiological mechanisms will likely guide the design of novel drugs that are based on oxytocin, but that possess improved efficacy and/or safety.

 描述（由适用提供）：非常需要改善精神分裂症（SCZ）的治疗方法，尤其是因为其“负面”症状和认知缺陷。催产素是一种生殖马酮，也是与SCZ非常相关的大脑过程的强大调节剂。对动物和人类的初步研究表明，氧气系统可能是开发新SCZ治疗的吉祥靶标。但是，为了实现这一目标，迫切需要对氧气潜在的抗SCZ效应有更深入的了解，以解决现有数据体中的不一致和差距。动物研究是获取有关潜在新疗法的信息的重要工具，但是令人惊讶的是，动物研究对氧气的抗SCZ潜力很少。该项目的总体目的是解决知识的关键差距。由于尚不清楚氧气可能会受益于哪些特定特征F SCZ，因此经过深思熟虑地设计了一些实验，以评估其在一系列最先进的动物测试中的影响，以代表SCZ认知和负面症状的独特临床特征。其他实验旨在揭示氧基抗SCZ效应的生物机制和脑回路的生物环路和脑回路，这是以前尚未很好地研究的。通过通过鼻内途径测试长期氧处理的作用，人类研究的标准途径，这些实验将提供对氧作用的理解，该作用与临床治疗的慢性性质相比，与以前的动物研究相比，该主题通常检查了一次性的一次性或中央氧气。由于它高度参与了生殖功能，因此氧气的大脑影响可能在MAES和女性中有所不同，但是研究其与SCZ相关作用的动物实验几乎仅包括男性受试者。通过将女性和雄性动物同时纳入实验，该项目将提供有关氧气抗SCZ效应中可能性别差异的急需信息。该项目的另一个重要特征是，它将推动与SCZ相关的承诺大鼠模型的表征，并促进用于模拟SCZ特征的测试的有效性的最终评估。该项目将大大扩展有关氧气抗SCZ特性的当前科学知识，包括有关其临床作用的潜在剂量，性别和时间依赖性方面的重要信息，潜在的不良影响以及个人特征，这些特征可能会识别出可能响应氧cin治疗的响应者。这些发现将指导对动物和SCZ患者的未来研究，而有关氧加毒素神经生​​物学机制的发现可能会指导基于氧加毒素的新型药物的设计，但具有提高的效率和/或安全性。