MOLECULAR BASIS OF OPIOID PHARMACODYNAMICS

阿片类药物药效学的分子基础

• 批准号: 2897579
• 负责人: Charles E Inturrisi
• 金额: $ 10.77万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2897579
• 关键词: NMDA receptors; RNase protection assay; antisense nucleic acid; drug addiction; drug tolerance; endogenous opioid; ethology; gene expression; gene targeting; genetically modified animals; laboratory mouse; laboratory rat; neural plasticity; pharmacokinetics; ribozymes; tissue /cell culture

DESCRIPTION: (Applicant's Abstract) This is a request for a renewal of a Research Scientist Award to allow me to continue to pursue the acquisition of techniques of molecular biology and neuroscience and to allow me to apply them to two NIDA funded research projects. Both projects are designed to test the hypothesis that Excitatory Amino Acid (EAA) receptors mediate the neuronal plasticity that is manifest as opioid tolerance and dependence or as certain types of nociceptive behavior. The first project will use NMDA and non-NMDA receptor antagonists and agonists as well as antisense or ribozymes targeted to NMDA receptors in selected animal behavioral paradigms to demonstrate the role of EAA receptors in opioid tolerance and nociception. Molecular and biochemical techniques will be used to identify and localize to neuroanatomical areas, the changes in gene expression that are associated with opioid tolerance or nociceptive behaviors. To complement and extend these approaches, opioid tolerance, dependence and nociceptive behaviors will be measured in knockout mice engineered with an absent or mutated EAA receptor. The second project will determine, in cultured cells expressing functional NMDA and opioid (mu or delta) receptors, the role of NMDA receptors in the changes that occur in opioid receptor signal transduction as a result of the exposure of these cells to opioids. The acquisition of molecular techniques, including, those related to gene targeting will be accomplished through sabbatical research in a laboratory where I can be directly involved in the design, production and evaluation of EAA receptor knockout mice. This RSA award will also allow me to maintain the reduction in teaching and administrative responsibilities that have for the past four years, significantly increased the time I can devote to enhancing my scientific skills.

描述：（申请人摘要） 这是一项延长研究科学家奖的请求，以便我能够 继续追求获得分子生物学技术和 神经科学，并允许我将它们应用到 NIDA 资助的两项研究中 项目。 这两个项目都是为了检验兴奋性的假设 氨基酸 (EAA) 受体介导明显的神经元可塑性 作为阿片类药物的耐受性和依赖性或某些类型的伤害性感受 行为。 第一个项目将使用NMDA和非NMDA受体拮抗剂 和激动剂以及针对 NMDA 受体的反义或核酶 选择动物行为范例来证明 EAA 的作用 阿片类药物耐受和伤害感受的受体。 分子和生化 技术将用于识别和定位神经解剖区域， 与阿片类药物耐受性相关的基因表达变化或 伤害性行为。 为了补充和扩展这些方法，阿片类药物 耐受性、依赖性和伤害性行为将在淘汰赛中进行测量 EAA 受体缺失或突变的小鼠。 第二个项目将确定在培养细胞中表达功能性 NMDA 和阿片类（mu 或 delta）受体，NMDA 受体在 阿片受体信号转导发生的变化 这些细胞暴露于阿片类药物。 获得分子技术，包括与基因相关的技术 将通过实验室的休假研究来完成目标确定 在这里我可以直接参与设计、制作和评估 EAA受体基因敲除小鼠。 这个 RSA 奖项也将使我能够继续减少教学和 过去四年的行政职责， 显着增加了我可以用于提高我的科学水平的时间 技能。