POSTNATAL TARGETING OF STRIATAL OPIOID & NMDA RECEPTORS

产后纹状体阿片类药物的靶向

• 批准号: 6379150
• 负责人: HONG WANG
• 金额: $ 21.19万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379150
• 关键词: NMDA receptors; antireceptor antibody; caudate nucleus; developmental neurobiology; immunocytochemistry; laboratory rat; opioid receptor; receptor binding; receptor expression

DESCRIPTION: (Adapted from the applicant's Description) The targeting of opioid receptors, as well as their coordinated interactions with N-methyl-D-aspartate subtype of glutamate receptors (NMDARs), is crucial for normal brain development and motor functions involving patch-matrix compartments in the mammalian caudate-putamen nucleus (CPN). During the critical developmental plasticity period, mu and delta opioid receptors (MOR, DOR) play either complementary or opposite roles that may in part involve functional interaction with NMDAR. The goal of this application is to test the hypothesis that there are age-related differences in the subcellular localization of MOR and/or DOR, which are correlated with synaptogenesis and parallel those of NMDAR in the CPN. The specific aims in each of the three proposed studies will be pursued by examining the localization of sequence specific antipeptide antisera against MOR, DOR, or NMDAR in the rat CPN during postnatal ontogeny. The results obtained from these studies will complement and extend previous knowledge that age-dependent MOR and DOR subcellular distributions are functionally linked to neuronal maturation; that developing NMDAR is largely involved in activity-dependent synaptic plasticity and has a subcellular distribution that parallels the distribution of opioid receptors; and that prenatal opioid availability differentially controls the ontogeny of neurons containing opioid and/or glutamate receptors. Understanding opioid and NMDA receptor targeting during development in the rat model may provide information leading to new approaches for reactivation of developmental plasticity in human brain.

描述：(根据申请者的描述改编)目标 阿片受体及其与受体的协调作用 N-甲基-D-天冬氨酸受体亚型(NMDARs)是 涉及斑块矩阵的正常脑发育和运动功能 哺乳动物尾壳核(CPN)内的隔室。在.期间 关键发育可塑性时期，单位和增量阿片受体(MOR， DOR)扮演互补或相反的角色，这可能部分涉及 与NMDAR的功能交互作用。此应用程序的目标是测试 亚细胞内存在年龄相关差异的假说 MOR和/或DOR的定位，与突触发生和 与CPN的NMDAR并驾齐驱。三者中每一个的具体目标 拟议的研究将通过检查序列的本地化来进行 大鼠CPN中抗MOR、DOR或NMDAR的特异性抗肽抗血清 出生后个体发育。从这些研究中获得的结果将是补充的 并扩展了先前的知识，即依赖于年龄的MOR和DOR亚细胞 分布在功能上与神经元成熟有关；即发育 NMDAR主要参与依赖活动的突触可塑性，并具有 与阿片受体分布平行的亚细胞分布； 而产前阿片类药物的可获得性不同地控制着 含有阿片和/或谷氨酸受体的神经元。对阿片类药物的认识 在大鼠模型的发育过程中，NMDA受体靶向可能提供 导致重新激活发展的新方法的信息 人脑的可塑性。