CALCIUM SIGNALING AND PREFRONTAL DEFICITS IN SCHIZOPHRENIA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 这个项目是来自耶鲁大学康特中心资助的一个项目。安非他明致敏已被提议作为精神病的非人灵长类动物模型。 该中心的耶基斯部分将研究安非他明致敏对猴子前额皮质多巴胺信号的影响。 恒河猴将接受安非他明治疗的致敏方案。 致敏动物的组织将分发给中心的其他研究者进行研究。 此外，我们将使用免疫电镜和定量分析在我们的实验室开发的研究D1家族多巴胺受体和信号转导蛋白在正常猴前额叶皮层和致敏动物的皮质中的分布。 我们将测试这一假设，即安非他明致敏后皮质多巴胺神经传递的失调伴随着多巴胺信号转导机制的结构变化。 这些研究将为理解抗精神病药物治疗动物的后续工作提供基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is a subcontract from a Conte Center grant based at Yale University. Amphetamine sensitization has been proposed as a nonhuman primate model of psychosis. The Yerkes component of this Center will examine the effect that amphetamine sensitization has on dopamine signaling in the prefrontal cortex of the monkey. Rhesus monkeys will undergo a sensitizing regimen of amphetamine treatment. Tissue from sensitized animals will be distributed to other investigators in the Center for study. In addition, we will use immunoelectron microscopy and quantitative analyses developed in our laboratory to study the distribution of D1 family dopamine receptors and signal transduction proteins in normal monkey prefrontal cortex and in the cortex of sensitized animals. We will test the hypothesis that dysregulation of cortical dopamine neurotransmission following amphetamine sensitization is accompanied by structural changes in the machinery of dopamine signal transduction. These studies will provide a basis for understanding subsequent work in antipsychotic treated animals.