Antidepressant-Like Effect of Low-Intensity Transcranial Ultrasound Stimulation

<italic>Objective:</italic> 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. <italic>Methods:</italic> 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). <italic>Results:</italic> 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 <inline-formula><tex-math notation="LaTeX">$({{88.8}}\% \pm {{2.5}}{\%, \text{n}}= {{16)}}$</tex-math></inline-formula> than LT-Res-ShamTUS group <inline-formula><tex-math notation="LaTeX">$({{72.8}}\% \pm {{7.2}}{\%, \text{n}}= {{16)\,(p}}= {{0.046}})$</tex-math></inline-formula>. Furthermore, the brain derived neurotrophic factor expression in left hippocampus was significantly promoted in LT-Res-TUS group <inline-formula><tex-math notation="LaTeX">$({{1.53}}\pm {{0.096}}{,\text{n}}= {{5)}}$</tex-math></inline-formula> compared to LT-Res-ShamTUS group <inline-formula><tex-math notation="LaTeX">$({{0.79}}\pm {{0.054}}{,\text{n}}= {{5)\,(p}}= {{0.009}})$</tex-math></inline-formula>. In addition, the histologic results of hematoxylin and eosin staining showed no TUS-induced brain tissue injury. <italic>Conclusion:</italic> These results demonstrated that low intensity TUS had antidepressant-like effect. <italic>Significance:</italic> 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.

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