Low Field Magnetic Stimulation in a Rodent Model of Depression

描述(由申请人提供)：这是一个两年的资金申请，以支持最近发现的一种治疗抑郁症的低场磁刺激(LFMS)疗法的研究。这种LFMS疗法使用低电磁场，施加特定的定时波形，以改善情绪。我们将研究电磁场的各种定时参数的重要性，并将使用抑郁症的动物模型--强迫游泳测试(FST)来评估每个参数在其改变时的重要性。我们将使用成年Spraogue-Dawley大鼠研究这种效应。这项研究的结果将被用于优化LFMS治疗抑郁症的方法。我们计划使用动物模型在受试者中非常快速的更替，以便检查计时波形的大量参数。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。之前的结果是使用磁共振成像系统(用于人类受试者)或备用磁线圈(用于动物实验)获得的。新的LFMS1装置的设计是为了为治疗和实验提供最佳的视野。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塞帕明进行既定的FST测试，以验证和校准我们的方法。在第二个实验中，我们将使用原型LFMS设备复制我们最初的LFMS FST结果，以建立结果的连续性。在第三节中，我们将重复第二节的实验，但将使用新的LFMS1设备作为其性能的验证。LFMS1装置已经在实验室中进行了现场设计验证。在第四节，也是最广泛的一节中，我们将逐一改变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。所有实验都将在假控制、完全盲目的设计中进行。实验将以16只大鼠为单位进行，其中8只大鼠被分配到LFMS，8只被分配给Sham。动物被放置在LFMS设备中进行治疗或伪装，处于受限但清醒的状态。LFMS治疗包括30高斯数量级的磁场，1伏/米数量级的电场，以及1 kHz数量级的定时。公共卫生相关性：这是一项关于不同治疗参数对低场磁刺激(LFMS)治疗抑郁症的意义的调查。在这项研究中，我们使用了一种大鼠抑郁的动物模型-强迫游泳测试，以通过一次一个地测试现有LFMS治疗参数的时间参数来检查它们的意义。这一结果将提供对LFMS治疗的更好理解，并将用于未来LFMS治疗在人体中的临床试验。使用动物模型是因为可以快速评估治疗参数的变化；对人类受试者进行同样的研究是不切实际的，因为需要大量的受试者。

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.