CONSTITUTIVELY ACTIVE DOPAMINE D1 AND D2 RECEPTORS

组成型活性多巴胺 D1 和 D2 受体

• 批准号: 6392314
• 负责人: QUN-YONG ZHOU
• 金额: $ 10.64万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6392314
• 关键词: animal developmental psychology; behavior test; behavioral genetics; developmental neurobiology; dopamine receptor; gene mutation; genetically modified animals; laboratory mouse; neurogenetics; protein isoforms; receptor binding; receptor expression; tissue /cell culture; transfection /expression vector

DESCRIPTION (Adapted from applicant's abstract): The long-term objective of this project is to further our understanding of the physiological role of dopamine D1 and D2 receptors in normal CNS function and in the functional pathologies associated with schizophrenia and other mental health disorders. Evidence put forth by a number of investigators suggests that the overactivation of dopaminergic synaptic transmission may be important in the pathophysiology of schizophrenia. The precise relation of dopamine overactivation to schizophrenia, however, remaines vague. The present series of studies seeks to bridge this gap by investigating the consequences of overactivated dopamine systems on brain development and function by genetic manipulation of dopamine receptors, and by identifying the consequences of expression of mutant dopamine receptors in transgenic animals. In brief, these studies seek (a) to create constitutively active mutants of dopamine D1 and D2 receptors and to identify their pharmacological and biochemical characteristics, (b) to introduce selected constitutively active D1 and D2 receptor mutants into transgenic mice, (c) to characterize developmental abnormalities in animals with overactivated dopamine systems, and (d) to identify behavioral abnormalities in mice with constitutively active dopamine receptors. The studies will enhance our understanding of D1 and D2 receptors at the molecular level, lead to a better understanding of the action mechanisms for dopamine receptors, and may lead to the development of improved pharmacotherapies for dopamine system malfunctions. These studies will also lead to a better understanding of the developmental and functional consequences of dopamine overactivation and should provide us with some fundamental information pertaining to the relation of dopamine neurotransmission malfunctions with the development of the behavioral malfunctions underlying complex mental health disorders.

描述（改编自申请人的摘要）：长期目标 这个项目是为了进一步我们对生理作用的理解 多巴胺 D1 和 D2 受体在正常中枢神经系统功能和功能性 与精神分裂症和其他精神健康障碍相关的病理。 一些调查人员提出的证据表明， 多巴胺能突触传递的过度激活可能在 精神分裂症的病理生理学。 多巴胺的精确关系 然而，过度激活是否会导致精神分裂症，目前仍不清楚。 现在的 一系列研究试图通过调查后果来弥合这一差距 过度激活的多巴胺系统对大脑发育和功能的影响 多巴胺受体的基因操作，并通过识别 转基因中突变多巴胺受体表达的后果 动物。 简而言之，这些研究寻求（a）创造本质上活跃的 多巴胺 D1 和 D2 受体突变体并鉴定其 药理和生化特性，（b）介绍选定的 将组成型活性 D1 和 D2 受体突变体导入转基因小鼠中，(c) 表征过度激活动物的发育异常 多巴胺系统，以及（d）识别小鼠的行为异常 组成型活性多巴胺受体。 这些研究将增强我们的 在分子水平上对 D1 和 D2 受体的了解，导致 更好地了解多巴胺受体的作用机制，以及 可能会导致改进多巴胺药物疗法的发展 系统故障。 这些研究也将带来更好的理解 多巴胺过度激活的发育和功能后果 并应向我们提供一些有关的基本信息 多巴胺神经传递功能障碍与发育的关系 复杂的心理健康障碍背后的行为障碍。