Identification of Cell Type-Specific Actions of Antipsychotic Drugs

抗精神病药物的细胞类型特异性作用的鉴定

• 批准号: 8328723
• 负责人: PAUL GREENGARD
• 金额: $ 198万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-29 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8328723
• 关键词: Adverse effects; Affect; Animal Model; Animals; Antipsychotic Agents; Behavioral Assay; Biochemical; Biological; Cells; Collaborations; Complex; Corpus striatum structure; Disease; Drug effect disorder; Etiology; Goals; Individual; Mental disorders; Molecular; Molecular Mechanisms of Action; Nature; Neuraxis; Neurons; Population; Property; Public Health; Reagent; Recording of previous events; Research; Resources; Rodent; Schizophrenia; Symptoms; Universities; cell type; innovation; medical schools; nervous system disorder; novel; novel therapeutics; public health relevance

DESCRIPTION (provided by applicant): Schizophrenia is one of the most debilitating psychiatric disorders, affecting approximately 1% of the population worldwide. A number of antipsychotic drugs are available but these are often ineffective and do not treat all the symptoms of the disease. New therapeutics are needed but their discovery has been hampered by a limited understanding of the etiology of this complex neurological disorder, and a lack of clear understanding of the precise molecular mechanisms of action of available antipsychotic drugs. One of the major limitations in identifying the molecular mechanisms of antipsychotic drug action has been the heterogeneous and intermixed cellular nature of the central nervous system. The major goal of the proposed studies in the Conte Center is therefore to achieve a complete understanding of the cellular and molecular actions of antipsychotic drugs through innovative approaches that use novel rodent animal models to allow analysis of individual types of neurons within cortico-striatal circuits. The Center Director and leader of Project 1 is Paul Greengard (Rockefeller University). The other Project leaders are: Nathaniel Heintz (Project 2, Rockefeller University); Angus Nairn (Project 3, Yale University); Eric Nestler (Project 4, Mount Sinai Medical School); and James Surmeier (Project 5, Northwestern University. There will also be an Animal Core, a Molecular & Biochemical Reagents Core, and an Administrative Core. The five Pis involved have an established history of effective collaboration and will use their complementary expertise and resources to take a multi-disciplinary approach in the proposed research. Through the use of biochemical, cell biological, molecular, electrophysiological, structural and behavioral assays, the proposed Conte Center will achieve a fuller understanding of the cellular and molecular actions of antipsychotic drugs in the cortico-striatal circuits. PUBLIC HEALTH RELEVANCE: Relevance to public health: Schizophrenia is a debilitating psychiatric disorder, and new therapies are needed. This Conte Center will characterize the effects of antipsychotic drugs on the properties of specific neuronal subtypes involved in schizophrenia, allowing for a complete understanding of the normal and maladaptive actions of these drugs, and leading to better therapies with higher efficacy and fewer side-effects.

描述（由申请人提供）：精神分裂症是最令人衰弱的精神疾病之一，影响了全球约1％的人口。有许多抗精神病药可用，但这些药物通常无效，并且没有治疗疾病的所有症状。需要新的治疗剂，但是由于对这种复杂神经系统疾病的病因的有限理解，并且缺乏对可用抗精神病药作用的精确分子机制的了解，因此阻碍了它们的发现。确定抗精神病药作用的分子机制的主要局限性之一就是中枢神经系统的异质和混合性细胞性质。因此，在孔戴中心提出的研究的主要目的是通过使用新颖的啮齿动物模型的创新方法来完全了解抗精神病药的细胞和分子作用，从而允许对皮质 - 差异电路中的单个神经元进行分析。项目1的中心主任和负责人是保罗·格林加德（Paul Greengard）（洛克菲勒大学）。其他项目负责人是：纳撒尼尔·海恩茨（Nathaniel Heintz）（洛克菲勒大学项目2）；安格斯·奈恩（Angus Nairn）（耶鲁大学项目3）；埃里克·纳斯特勒（Eric Nestler）（西奈山医学院项目4）；和詹姆斯·索尔米尔（James Surmeier）（项目5，西北大学。还将有一个动物核心，分子和生物化学试剂核心和行政核心。所涉及的五个PI具有有效协作的既定历史，并将利用其补充专业知识和资源在提议的研究中采用多学科研究。拟议的孔戴中心将对皮质 - 纹状体回路中抗精神病药的细胞和分子作用有更深入的了解。 公共卫生相关性：与公共卫生的相关性：精神分裂症是一种使人衰弱的精神疾病，需要新的疗法。该孔戴中心将表征抗精神病药对精神分裂症涉及的特定神经元亚型的特性的影响，从而完全了解这些药物的正常和不良适应性作用，并导致更好的治疗方法具有更高的效果，较少的副作用。