AN IMPLANTABLE BOLUS INFUSION PUMP FOR THE NEUROSCIENCES

描述：(改编自申请人摘要)申请人提出 皮下埋藏式微丸输液泵的研制 小动物的神经科学研究，研究范式要求 处于非拴系状态的有意识的、行为正常的动物。MIP将允许在体内 通过远程激活和顺序给药的递增剂量 通过颈外静脉给药不同的药物 静脉。这一能力将使MIP成为检查急性脑出血的强大工具 药物对大鼠行为和生理影响的实验研究 人类疾病。MIP的使用应该能够调查急性影响 对动物行为敏感的药理药物的研究 处理(例如，交配、攻击、睡眠、昼夜节律)。此外， MIP将允许对药物的急性影响进行非侵入性研究 通常会被搬运效果混淆的生理参数 对动物的压力(例如，应激激素、心血管参数、大脑 电活动、温度)。提供的试点数据表明， 在自由活动的动物体内注入放射性示踪剂和MIP允许 与脑相关的局部血流量急性变化的影像研究 激活。这种对复杂动物行为的功能神经成像不可能 用当前的技术进行的。在转基因小鼠中，MIP承诺 改进对基因表型效应的表征 删除/插入。本项目的4个目标是：(1)优化和 开发大鼠MIP的设计，(2)验证MIP的能力 在自由操作中提供精确的、远程激活的药物推注 大鼠，不干扰正常的行为和生理 参数，并允许生成脑血流图像，(3) 小鼠MIP小型化；(4)双室MIP的设计与测试 它允许两种独立的、受控的药物释放 探员们。

DESCRIPTION: (Adapted from the Applicant's Abstract) The applicants propose the development of a subcutaneously implantable microbolus infusion pump (MIP) for neuroscience research in small animals, where the research paradigms require conscious, behaving animals in a non-tethered state. The MIP will allow in vivo incremental dosing of drugs by remote activation, as well as sequential administration of different pharmacologic agents, via the external jugular vein. This capability will make the MIP a powerful tool for examining acute behavioral and physiologic effects of pharmacologic agents in animal models of human disease. Use of the MIP should allow investigations of the acute effects of pharmacologic agents on animal behaviors sensitive to interference by handling (e.g., mating, aggression, sleep, circadian rhythms). Furthermore, the MIP will allow noninvasive study of the acute effect of pharmacologic agents on physiologic parameters that are typically confounded by the effects of handling stress on the animal (e.g., stress hormones, cardiovascular parameters, brain electrical activity, temperature). Pilot data are provided which suggest that infusion of radiotracers with the MIP in the freely moving animal allows imaging of acute changes in regional blood flow associated with brain activation. Such functional neuroimaging of complex animal behaviors cannot be undertaken with the current technologies. In transgenic mice, the MIP promises to improve the characterization of the phenotypic effects of gene deletions/insertions. The 4 goals of this project are: (1) to optimize and develop the design of the MIP for rats, (2) to validate the ability of MIP to provide precise, remotely activated bolus infusion of a drug in freely behaving rats, without interfering with the normal behavior and physiological parameters, and allowing the generation of cerebral blood flow images, (3) to miniaturize the MIP for mice, and (4) to design and test a dual chamber MIP that allows independent, controlled release of two separate pharmacologic agents.