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There is an unmet need for better nonpharmaceutical treatments for depression. Low-intensity pulsed ultrasound (LIPUS) is a novel type of neuromodulation that could be helpful for depressed patients. The goal of this study was to investigate the feasibility and potential mechanisms of LIPUS in the treatment of depression. Chronic unpredictable stress (CUS) was used to generate rats with depression-like features that were treated with four weeks of LIPUS stimulation of the ventromedial prefrontal cortex. Depression-like behaviors were ass