Low Field Magnetic Stimulation in a Rodent Model of Depression

描述（由申请人提供）：这是一项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，该电磁场与特定的定时波形一起施加，以改善情绪。我们将研究电磁场的各种定时参数的意义，并将使用抑郁症的动物模型，强迫游泳试验（FST），以评估每个参数的意义，因为它是变化的。我们将使用成年Sprague-Dawley大鼠研究这种效应。本研究的结果将用于优化LFMS治疗抑郁症的人。我们计划使用动物模型使受试者的快速周转成为可能，以便检查定时波形的大量参数。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装置。先前的结果是使用MRI系统（用于人类受试者）或备用磁线圈（用于动物结果）获得的。为了给治疗和实验提供最佳视野，设计了新型LFMS 1装置。在本研究中，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。在第二部分中，我们将使用原型LFMS设备复制我们原始的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LFMS 1设备作为其性能的验证。LFMS 1装置已在实验室中对其现场设计进行了确认。在第四部分，也是最广泛的部分，我们将逐一改变LFMS治疗中的时间参数，并确定有效性的变化，以确定最佳治疗参数。所有实验均采用假手术对照、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只分配至假手术组。将动物置于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治疗涉及30高斯量级的磁场、1伏特/米量级的电场和1 kHz量级的定时。公共卫生相关性：这是一个调查的意义，不同的治疗参数的低场磁刺激（LFMS）治疗抑郁症。在本研究中，我们使用大鼠抑郁症动物模型，强迫游泳试验，通过一次测试一个，检查现有LFMS治疗参数的时间参数的意义。结果将提供对LFMS治疗的更好理解，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价治疗参数的变化;由于需要大量受试者，用人类受试者进行相同的研究是不切实际的。

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.