CONSTITUTIVELY ACTIVE DOPAMINE D1 AND D2 RECEPTORS

描述（改编自申请人摘要）：长期目标 这个项目是为了进一步了解我们的生理作用， 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学。 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 多巴胺与 然而，过度激活对精神分裂症的影响尚不明确。 本 一系列研究试图通过调查结果来弥合这一差距 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 转基因小鼠中突变多巴胺受体表达的后果 动物 简而言之，这些研究旨在（a）创造积极的组成 多巴胺D1和D2受体的突变体，并鉴定它们的 药理学和生物化学特征，（B）引入选择的 组成型活性D1和D2受体突变体转化到转基因小鼠中，（c） 描述过度激活的动物的发育异常 多巴胺系统，以及（d）鉴定具有以下特征的小鼠的行为异常： 组成型活性多巴胺受体 这些研究将提高我们的 在分子水平上理解D1和D2受体，导致 更好地了解多巴胺受体的作用机制， 可能会导致多巴胺药物治疗的改进 系统故障。 这些研究也将导致更好地了解 多巴胺过度激活对发育和功能的影响 应该能为我们提供一些基本信息 多巴胺神经传递功能障碍与 复杂心理健康障碍背后的行为障碍

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.