Low Field Magnetic Stimulation in a Rodent Model of Depression

抑郁症啮齿动物模型中的低场磁刺激

• 批准号: 7573798
• 负责人: MICHAEL L ROHAN
• 金额: $ 22.81万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7573798
• 关键词: Adult; Anatomy; Animal Model; Animals; Antidepressive Agents; Behavior; Bipolar Disorder; Blinded; Brain; Characteristics; Clinical Trials; Complex; Conscious; Dependence; Desipramine; Device Designs; Devices; Diving; Dose; Effectiveness; Electromagnetic Fields; Fluoxetine; Frequencies; Funding; Future; Head; Hospitals; Investigation; Laboratories; Learned Helplessness; Literature; Location; MRI Scans; Magnetic Resonance; Magnetic Resonance Imaging; Magnetism; Measures; Mental disorders; Methodology; Modeling; Moods; Neurologic; Norepinephrine; Pattern; Performance; Pharmaceutical Preparations; Physiologic pulse; Placebos; Rattus; Reporting; Request for Applications; Rodent Model; Scanning; Selective Serotonin Reuptake Inhibitor; Series; Speed; Sprague-Dawley Rats; Swimming; System; Test Result; Testing; Time; Validation; behavior test; depressed; depression; design; electric field; human subject; improved; inhibitor/antagonist; insight; magnetic field; meter; preclinical study; prototype; public health relevance; relating to nervous system; repetitive transcranial magnetic stimulation; research study; uptake

DESCRIPTION (provided by applicant): This is an application for two years of funding to support the investigation of a Low Field Magnetic Stimulation (LFMS) treatment for depression that was recently discovered. This LFMS treatment uses low level electromagnetic fields that are applied with a specific timing waveform in order to improve mood. We will investigate the significance of the various timing parameters of the electromagnetic fields and will use an animal model of depression, the Forced Swim Test (FST) to evaluate the significance of each parameter as it is changed. We will study this effect using adult Sprague-Dawley rats. The results of this study will be used to optimize the LFMS treatment of depression in people. We plan to use the very fast turnover in subjects that an animal model makes possible in order to examine a large number of parameters for the timing waveform. In this way we hope to characterize some of the behavior of this effect, and gain insight into some potential mechanisms of interaction with the brain. We have recently designed a new LFMS device. Previous results were obtained using an MRI system (for human subjects) or a spare magnetic coil (for animal results). The new LFMS1 device was designed in order to provide optimal fields for treatment and experiment. In our study we will have four sections of experiments. In the first we will perform established FST tests of known antidepressant medications, fluoxetine and desipramine, in order to validate and calibrate our methodology. In the second we will replicate our original LFMS FST results using the prototype LFMS device, in order to establish continuity of results. In the third section we will duplicate the second section experiments but will use the new LFMS1 device as a validation of its performance. The LFMS1 device has already been validated with respect to its field design in the laboratory. In the fourth and most extensive section we will vary the timing parameters in the LFMS treatment one by one and determine the change in effectiveness in order to determine the optimum treatment parameters. All experiments will be performed in a sham controlled, fully blinded design. Experiments will be performed in units of sixteen rats, with 8 rats assigned to LFMS and 8 assigned to sham. Animals are placed in the LFMS device for treatment or sham in a restrained but conscious state. LFMS treatments involve magnetic fields on the order of 30 Gauss, electric fields on the order of 1 Volt/meter, and timing on the order of 1 kHz. PUBLIC HEALTH RELEVANCE: This is an investigation of the significance of different treatment parameters for the Low Field Magnetic Stimulation (LFMS) treatment for depression. In this study we are using an animal model of depression in rats, the Forced Swim Test, in order to examine the significance of the timing parameters of the existing LFMS treatment parameter by testing them one at a time. The results will provide a better understanding of the LFMS treatment, and will be used in future clinical trials of LFMS treatments in human subjects. Animal models are used because it is possible to evaluate the changes in treatment parameters quickly; performing the same study with human subjects would be impractical because of the large number of subjects required.

描述（由申请人提供）：这是一份为期两年的资助申请，用于支持最近发现的低场磁刺激（LFMS）治疗抑郁症的研究。这种 LFMS 治疗使用低水平电磁场，并以特定的时序波形施加，以改善情绪。我们将研究电磁场的各种计时参数的重要性，并将使用抑郁症动物模型、强迫游泳测试 (FST) 来评估每个参数变化时的重要性。我们将使用成年斯普拉格-道利大鼠来研究这种效应。这项研究的结果将用于优化 LFMS 对抑郁症的治疗。我们计划利用动物模型所实现的受试者快速周转来检查时序波形的大量参数。通过这种方式，我们希望描述这种效应的一些行为，并深入了解与大脑相互作用的一些潜在机制。我们最近设计了一种新的 LFMS 设备。之前的结果是使用 MRI 系统（针对人类受试者）或备用磁线圈（针对动物结果）获得的。新的 LFMS1 设备的设计目的是为治疗和实验提供最佳的场地。在我们的研究中，我们将有四个部分的实验。首先，我们将对已知的抗抑郁药物、氟西汀和地昔帕明进行既定的 FST 测试，以验证和校准我们的方法。在第二步中，我们将使用原型 LFMS 设备复制原始 LFMS FST 结果，以建立结果的连续性。在第三部分中，我们将重复第二部分的实验，但将使用新的 LFMS1 器件来验证其性能。 LFMS1 设备的现场设计已在实验室得到验证。在第四部分也是最广泛的部分中，我们将一一改变 LFMS 治疗中的计时参数，并确定有效性的变化，以确定最佳治疗参数。所有实验都将以假对照、全盲设计进行。实验将以 16 只大鼠为单位进行，其中 8 只大鼠分配至 LFMS，8 只分配至假大鼠。将动物放置在 LFMS 装置中进行治疗或在受约束但有意识的状态下进行假手术。 LFMS 处理涉及 30 高斯量级的磁场、1 伏/米量级的电场以及 1 kHz 量级的定时。公共健康相关性：这是一项针对低场磁刺激 (LFMS) 治疗抑郁症的不同治疗参数的重要性的调查。在这项研究中，我们使用大鼠抑郁症动物模型，即强迫游泳测试，通过一次测试一个来检验现有 LFMS 治疗参数的时间参数的重要性。结果将有助于更好地了解 LFMS 治疗，并将用于未来 LFMS 治疗人类受试者的临床试验。使用动物模型是因为可以快速评估治疗参数的变化；由于需要大量受试者，因此对人类受试者进行相同的研究是不切实际的。