Chronic Dose effects of Reboxetine on Motor Skill Acquisition and Cortical Excitability

Background: Enhancement of cortical excitability is thought to be potentially beneficial for synaptic plasticity as, e.g., associated with motor skill acquisition. The selective norepinephrine re-uptake inhibitor reboxetine (RBX) might therefore be able to facilitate functional recovery after brain lesions. Considering patient administration in the future we studied the effects of a chronic dose regimen on motor skill acquisition and cortical excitability. Methods: The study was randomized, double blind and placebo-controlled. 12 healthy subjects received 4mg RBX twice a day for 4 full days preceded by 2mg RBX twice a day for 2 days. Each subject served as its own control. There were at least 16 days between the verum and the placebo session. Measurement of cortical excitability by means of paired pulse transcranial magnetic stimulation (ppTMS) was conducted before and after the motor skill acquisition task for each session. The task was to lift two fingers of the right hand at once while the hand positioned sprawled out on the table. The movements were self-paced and subjects had to perform as many moves as possible in 60 seconds. Between 7 blocks of self-paced movements 6 blocks with 60 single trials at a fixed interstimulus interval were presented. Two equally difficult versions of the task using different finger combinations were established in order to avoid carryover effects in performance. The finger movements were recorded with a three-dimensional ultrasound movement analysis system (Zebris). Results: All subjects had a substantial gain in performance over the self-paced blocks. Average increase in number of correct moves was 87% (from 27.8 to 51.9). There was no significant difference either between the versions of the task or between placebo vs. verum. Also, there was no significant difference between first and second session, indicating that there was no carryover effect in performance. ppTMS revealed no significant differences in cortical excitability between groups. Conclusion: The newly developed skill acquisition task yields a robust single session gain of performance. As the two versions of the task do not interact, it is suitable to be used in cross-over designs. In contrast to studies using single doses of RBX, motor cortex excitability seems to be unaffected in a chronic dose steady-state. This could explain why motor behavior was not modulated by the study medication.