Scientific Core

药物滥用的分子靶点及其相关的细胞内信号转导途径研究 已经产生了关于与这些药物相关的细胞扰动的丰富信息。这个 项目I-IV中概述的联合研究将在现有知识的基础上扩展严格的细胞生物学， 药物治疗对神经细胞的分子、生化、行为和电生理研究。这些 研究有可能为药物依赖的原因提供更多的洞察力，并阐明 可能成为药物干预的新靶点。 科学核心将是一个致力于促进项目I-IV中提议的实验的中心 这需要使用转基因动物、酵母双杂交筛选和各种关键的生物试剂。 这些项目中概述的实验需要创造和维护大量的基因 经过改良的动物。必要转基因小鼠的建立和鉴定，以及维持 这些和所有其他转基因小鼠是核心的具体目标I。以帮助识别和描述 核心将设计与滥用药物靶向的信号分子相关的新的蛋白质-蛋白质相互作用 并在特定目标II中进行酵母双杂交筛选。此外，科学核心将是 项目I-IV中概述的实验所需的各种试剂。关键蛋白质、酶和抗体 将在特定的AIM III中产生，而新的多克隆抗体，包括磷酸化状态- 特定的抗体，将在特定的目标IV产生。

Investigations into the molecular targets of drugs of abuse and their associated intracellular signaling pathways have yielded a wealth of information regarding the cellular perturbations associated with these drugs. The combined studies outlined in Projects I-IV will extend upon this existing knowledge with rigorous cell biological, molecular, biochemical, behavioral, and electrophysiological studies of neuronal cells upon drug treatment. These studies have the potential to provide greater insights into the causes of drug dependence as well as to elucidate possible novel targets for pharmacological intervention. The Scientific Core will be a center devoted to facilitating those experiments proposed in Projects I-IV that require the use of genetically modified animals, yeast two-hybrid screens, and various key biological reagents. The experiments outlined in these Projects require the creation and maintenance of large numbers of genetically modified animals. The creation and characterization of necessary transgenic mice, and the maintenance of these and all other genetically modified mice is Specific Aim I of the Core. To help identify and characterize novel protein-protein interactions relevant to signaling molecules targeted by drug of abuse, the Core will design and execute yeast two-hybrid screens in Specific Aim II. In addition, the Scientific Core will be a key source of various reagents needed for the experiments outlined in Projects I-IV. Key proteins, enzymes, and antibodies will be produced in Specific Aim III,while new polyclonal antibodies, including phosphorylation state- specific antibodies, will be produced in Specific Aim IV.