FUNCTIONS OF BIOGENIC AMINE TRANSPORTERS

描述：（申请人摘要） 生物胺转运蛋白是可卡因，安非他明， 和抗抑郁药 我的长远目标是了解 这些转运蛋白的功能和机制，特别是它们在 滥用药物成瘾和治疗药物的作用。 一 导师研究科学家发展奖将让我学习新的 研究生物胺体内功能所必需的技术 运输商，并获得进一步的经验，然后才开始全面 独立研究计划。 生物胺转运蛋白已被研究 广泛用于组织制备和培养细胞，并间接用于 整个动物使用化合物来阻断这些转运蛋白。 唯一的 对运输者作用的直接评估是最近对 转基因小鼠的多巴胺转运蛋白。 尽管新的重大 从这项研究中了解到的信息，广泛的适应变化已经确定， 研究的局限性。 因此，我们建议设计一种诱导型 反义抑制系统来研究生物胺转运蛋白。 在 通过这种方法，反义RNA将以改善的 基于四环素操纵子的可诱导系统， 以可控和可逆的方式输送。 我们将评估 该方法首先在培养细胞中的有效性，然后在 转基因小鼠 然后，我们将使用这种方法来调查 动物的生理和行为变化。 我们希望提供新的 关于整个动物中转运蛋白功能的信息， 它们在药物滥用成瘾中的作用和治疗作用 抗抑郁药 从这些研究中获得的知识最终可能 从而导致更好地治疗吸毒成瘾、抑郁症和其他 相关疾病。

DESCRIPTION: (Applicant's Abstract) Biogenic amine transporters are the main targets of cocaine, amphetamines, and antidepressants. My broad, long-term objectives are to understand the functions and mechanisms of these transporters, specifically their roles in the addiction to drugs of abuse and the actions of therapeutic drugs. A Mentored Research Scientist Development Award will allow me to learn new techniques necessary to study the in vivo functions of the biogenic amine transporters and to gain further experience before embarking on a fully independent research program. Biogenic amine transporters have been studied extensively in tissue preparations and cultured cells, and indirectly in whole animals using compounds that block these transporters. The only direct assessment of the roles of the transporters is the recent knockout of dopamine transporter in transgenic mice. Despite the significant new information learned from this study, extensive adaptation changes have set limitations to the study. Therefore, we propose to engineer an inducible antisense suppression system to study the biogenic amine transporters. In this approach, an antisense RNA would be expressed with an improved tetracycline operon based inducible system to suppress a specific transporter in a controllable and reversible manner. We will evaluate the effectiveness of the approach in cultured cells first, and next in transgenic mice. Then we will use this approach to investigate the physiologic and behavioral changes of the animals. We hope to provide new information about the functions of the transporters in whole animals and their roles in the addiction to drugs of abuse and the therapeutic actions of antidepressants. The knowledge gained from these studies may eventually lead to better approach to treat drug addictions, depression and other related diseases.