AN IMPLANTABLE BOLUS INFUSION PUMP FOR THE NEUROSCIENCES

描述：（改编自申请人的摘要）申请人提出了 皮下植入式微团输注泵（MIP）的开发， 小动物神经科学研究，研究范式需要 有意识有行为的动物处于非束缚状态MIP将允许在体内 通过远程激活的药物增量给药，以及 通过颈外静脉给予不同的药物 静脉这种能力将使MIP成为检查急性 药物在动物模型中的行为和生理作用 人类疾病MIP的使用应允许调查急性效应 药物对动物行为的影响 处理（例如，交配、攻击、睡眠、昼夜节律）。而且 MIP将允许非侵入性研究药理学药物对 生理参数通常会受到操作影响的混淆 对动物的压力（例如，应激激素，心血管参数，脑 电活动、温度）。提供的试点数据表明， 在自由活动的动物中注入具有MIP的放射性示踪剂允许 与脑相关的局部血流急性变化的成像 activation.这种对复杂动物行为的功能性神经成像， 用现有的技术。在转基因小鼠中，MIP承诺 改善基因的表型效应的表征 删除/插入。本项目的4个目标是：（1）优化和 建立大鼠MIP的设计，（2）验证MIP的能力， 提供精确的、远程激活的药物推注， 大鼠，不干扰正常行为和生理 参数，并允许生成脑血流图像，（3） 设计并测试了双腔MIP 它允许两种单独的药理学作用的独立的受控释放， 剂.

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.