Effects of low-frequency repetitive transcranial magnetic stimulation on depression- and anxiety-like behaviors in epileptic rats

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been considered as a treatment option for depression and anxiety. However, its role in epilepsy comorbid with depression and anxiety is unclear. Therefore, we evaluated whether low-frequency rTMS can alleviate depression- and anxiety-like behavior in epileptic rats. Forty-eight adult rats were allocated at random to four groups: Control, Pentylenetetrazol (PTZ), PTZ-rTMS and PTZ-Sham. The control group received intraperitoneal injections of normal saline, while the other groups received intraperitoneal injections of pentylenetetrazol (35 mg/kg/d) once a day for 15 days. Low-frequency rTMS or sham stimulation were administered to the PTZ-rTMS and PTZ-Sham group, respectively, over the two-week period. The open-field test (OFT), elevated plus-maze test (EPM) and forced swimming test (FST) were carried out before the experiment, on the 8th and 15th day to assess depression- and anxiety-like behavior in the rats. Two weeks of low-frequency rTMS treatment could not impair the increases of seizure severity in epileptic rats. However, relative to the PTZ and PTZ-Sham group, the two-week low-frequency rTMS treatment significantly reduced the immobility time in the forced swimming test and attenuated the progressive decrease in total distance traveled, frequency of rearing, velocity in the open-field test, number of entries in the open arms (%) and the time spent in the open arms (%) in the elevated plus-maze test of the PTZ-rTMS group. We proposed that low-frequency rTMS can benefit epileptic rats via amelioration of comorbid depression and anxiety, but it can not alleviate the seizure severity.