Ultrasound neuromodulation ameliorates chronic corticosterone-induced depression- and anxiety-like behaviors in mice

Objective.Monoamine dysfunction has been implicated as a pathophysiological basis of several mental disorders, including anxiety and depression. Transcranial ultrasound stimulation (TUS) is a noninvasive nerve stimulation technic showing great potential in treating depression/anxiety disorders. This study aims to investigate whether TUS can ameliorate depression with anxiety in mice by regulating brain monoamine levels.Approach.Mice received repeated subcutaneous injections of corticosterone (CORT, 20 mg kg-1) for 3 weeks to produce depression- and anxiety-like behaviors. Ultrasound stimulated the dorsal lateral nucleus (DRN) for 30 min daily for 3 weeks without interruption of CORT injection. Behavioral phenotypes of depression and anxiety were estimated by sucrose preference test (SPT), tail suspension test (TST), and elevated plus-maze test (EPM). Liquid chromatography-mass spectrometry (LC-MS) was used to quantify brain levels of serotonin (5-HT), norepinephrine (NE), and dopamine (DA). Western blotting was performed to detect brain-derived neurotrophic factor (BDNF) levels in hippocampal.Main results.TUS of DRN significantly ameliorated the depression-like behaviors in SPT (p= 0.0004) and TST (p= 0.0003) as well as anxiety-like behaviors in EPM (open arm entry frequencies,p< 0.05). Moreover, TUS increased c-Fos-positive cell expression (p= 0.0127) and induced no tissue damage. LC-MS results showed TUS of DRN resulted in a non-significant increase in the 5-HT levels and a significant decrease in the NE levels, but did not affect the levels of DA and BDNF.Significance.These results suggest TUS of DRN has safely and effectively ameliorated CORT-induced depression- and anxiety-like behaviors, possibly by restoring brain levels of 5-HT and NE. TUS may be a safe and effective technique for remedying depression and anxiety comorbidity.