Therapeutic effects of transcranial direct current stimulation on ketamine-induced schizophrenia-like behaviors and oxidative stress

In a mouse model of schizophrenia induced by ketamine, 0.5 mA anodal transcranial direct current stimulation (tDCS) applied for 30 minutes daily for 7 days reduced schizophrenia-like behaviors and oxidative stress. Mice that received ketamine showed increased locomotor activity, depressive and anxiety-like behaviors, and impaired learning, along with decreased total antioxidant capacity and increased total oxidant capacity in the prefrontal cortex and hippocampus. tDCS reversed these effects: it reduced abnormal behaviors, improved learning, and restored antioxidant balance. The findings suggest tDCS modulates NMDA receptors in the glutamatergic pathway to produce these benefits.

Study at a glance

Abstract

Schizophrenia is a serious neuropsychiatric disorder that affects 1% of the world's population. It plays an important role in psychiatric symptoms, including major depression and schizophrenia. However, it is also known that one of the main reasons underlying the pathogenesis of schizophrenia is oxidative stress. Transcranial direct current stimulation (tDCS) has recently been a promising method for modifying neuronal membrane stimulation, cognition, and behavioral function. Our aim in this study is to explore the effects of 0.5 mA anodal tDCS stimulation on schizophrenia-like behaviors and oxidative stress in a ketamine-induced schizophrenia model. 30 male Balb/C mice were divided into 3 groups as control, schizophrenia, and schizophrenia+tDCS. The schizophrenia model was created by administering 25mg/kg/day ketamine for 7 days. tDCS treatment was performed by giving 0.5 mA anodal tDCS stimulation for 7 days. On day 14 of the experiment, SCZ-like behaviors were assessed using a novel object recognition test (NOR), open field test (OF), and tail suspension test (TST), and also oxidative stress in hippocampus and prefrontal tissues was estimated. Results showed that locomotor activity, depressive and anxiety-like behaviors of the schizophrenia group increased significantly compared to the control group and decreased after tDCS stimulation (p<0.05). In addition, it was investigated that tDCS stimulation also significantly increased learning that decreased after schizophrenia (p<0.05). All together, it was observed that the total antioxidant capacity of the schizophrenia group decreased while the total oxidant capacity of the schizophrenia group rose in the prefrontal cortex and hippocampus tissues compared to the control group (p<0.05). Otherwise, 0.5 mA anodal tDCS stimulation increased the total antioxidant capacity of the schizophrenia+tDCS group compared to the schizophrenia group, while it decreased total oxidant capacity (p<0.05). Based on our results displayed that 0.5 mA anodal tDCS stimulation for 30 minutes for 7 days reduced schizophrenia-like behaviors and oxidative stress by modulation of N-methyl-D-aspartic acid (NMDA) receptors in the glutamatergic pathway in a ketamine-induced, NMDA antagonist, schizophrenia model.