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.