The effect of repetitive transcranial magnetic stimulation on fear extinction in rats

Abstract Facilitating fear extinction is clinically important to improve the efficacy of current exposure therapies for the treatment of anxiety disorders, such as post-traumatic stress disorder (PTSD). The aim of this study was to determine if repeated transcranial magnetic stimulation (rTMS) facilitates fear extinction in rats, especially when paired with exposure to a conditioned stimulus (CS). Thirty-five rats were conditioned to a tone CS by pairing the tone with an electric foot shock as an aversive unconditioned stimulus (US). We assessed the effects of 10 Hz rTMS before fear extinction (experiment 1) and rTMS paired with CS during extinction (experiment 2) on the following day. Fear responses of the rats were estimated using the level of freezing upon tone stimulus and were compared between the rTMS and corresponding sham groups. The rats treated with rTMS before fear extinction showed no difference in freezing time when compared with the sham group. However, the rats treated with rTMS paired with CS during extinction showed significantly less freezing behavior than the sham group, and this enhancement of fear extinction remained after 24 h without further stimulation. This finding suggests that high-frequency rTMS paired with trauma-reminding stimuli enhances fear extinction and that rTMS in conjunction with exposure therapy is potentially useful for facilitating extinction memory in the treatment of PTSD.