Antidepressant-Like Effect of Low-Intensity Transcranial Ultrasound Stimulation

Transcranial ultrasound stimulation (TUS) is a noninvasive neuromodulation technique with good spatial resolution and deep penetration. This study aims to investigate whether TUS has antidepressant-like effect to depressed rats.Rats were divided into five groups, including two groups (ST-Ctr and ST-Res) for evaluating the short-term impact of restraint stress and three groups (LT-Ctr-ShamTUS, LT-Res-ShamTUS and LT-Res-TUS) for studying the long-term effects of restraint and TUS stimulation. The TUS-treated rats were subjected to 15 min TUS stimulation to the prelimbic cortex every day for 2 weeks after the restraint. Then, depressive symptoms related behavioral outcomes were estimated in ST-Ctr and ST-Res groups (1 week after restraint), as well as in the other three groups (3 weeks after restraint).The 48-h-restraint stress could lead to long lasting reduction of exploratory behavior (1 and 3 weeks after restraint) and protracted anhedonia (only observed 3 weeks after restraint). TUS application successfully reversed the core depressive phenotype, anhedonia, indicated by significantly higher sucrose preference index in LT-Res-TUS group [Formula: see text] than LT-Res-ShamTUS group [Formula: see text]. Furthermore, the brain derived neurotrophic factor expression in left hippocampus was significantly promoted in LT-Res-TUS group [Formula: see text] compared to LT-Res-ShamTUS group [Formula: see text]. In addition, the histologic results of hematoxylin and eosin staining showed no TUS-induced brain tissue injury.These results demonstrated that low intensity TUS had antidepressant-like effect.TUS has been speculated to have therapeutic effect in depression. This study provide evidence for the antidepressant-like effects of TUS in rats for the first time.