Continuous but not intermittent theta burst stimulation decreases striatal dopamine release and cortical excitability

Dopamine modulation is thought to underpin some of the therapeutic effects associated with repetitive transcranial magnetic stimulation (rTMS). However, patient studies have failed to demonstrate consistent changes in the dopamine system in vivo after a therapeutic course of rTMS. Here, we evaluated acute and chronic changes in striatal dopamine release elicited by a clinically relevant course of theta burst (TBS) or sham stimulation using [¹¹C]raclopride in healthy non-human primates (n = 11). Subjects were scanned immediately after the first session of TBS and the day after a 3 week course of daily TBS delivery. After experiment completion, animals were euthanized, and immunofluorescence staining was carried out using antibodies targeting D₂ receptors (D₂R). Continuous TBS (cTBS, an inhibitory form of rTMS) over the left primary motor cortex acutely decreased dopamine release bilaterally in the putamen. However, no significant changes in dopamine receptors nor D₂R immunoreactivity were noted 24 h after the last stimulation, while a decrease in cortical excitability, as measured by an increase in resting motor threshold, could still be quantified. On the opposite, intermittent TBS (iTBS, an excitatory form of rTMS) did not affect dopamine release, acutely or chronically, D₂R immunoreactivity or cortical excitability. These findings suggest that the long-term therapeutic effects of TBS might be facilitated through the modulation of different neurotransmission systems beyond the dopamine system. However, given the small sample size, these results should be interpreted with caution.