Antidepressant-Like Effect of Low-Intensity Transcranial Ultrasound Stimulation

Objective: 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. Methods: 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). Results: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 (88.8% ± 2.5%, n = 16) than LT-ResShamTUS group (72.8% ± 7.2%, n = 16)(p = 0.046). Furthermore, the brain derived neurotrophic factor expression in left hippocampus was significantly promoted in LT-Res-TUS group (1.53 ± 0.096, n = 5) compared to LT-Res-ShamTUS group (0.79 ± 0.054, n = 5) (p = 0.009). In addition, the histologic results of hematoxylin and eosin staining showed no TUS-induced brain tissue injury. Conclusion: These results demonstrated that low intensity TUS had antidepressant-like effect. Significance: 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.