Chronic dose effects of reboxetine on motor skill acquisition and cortical excitability

Enhancement of cortical excitability is thought to be beneficial for synaptic plasticity associated with motor skill acquisition. Single dose application of the selective norepinephrine reuptake inhibitor reboxetine (RBX) increases motor cortex excitability. In this study, we tested if a chronic dose application of RBX improved motor skill acquisition and modulated cortical excitability.

The study was randomised, double blind and placebo-controlled. Twelve healthy subjects received four milligram RBX twice a day for four days preceded by two milligram RBX twice a day for two days. Each subject served as his own control. The time interval between the verum and the placebo session was 16 days or more. Measurement of cortical excitability by means of paired pulse transcranial magnetic stimulation (ppTMS) was conducted before and after the motor skill acquisition task in each session. The task was to lift two fingers of the right hand at once while the hand was positioned sprawled out on the table. The movements were self-paced and subjects had to perform as many moves as possible in 60 sec. Between seven blocks of self-paced movements six blocks with 60 single trials at a fixed interstimulus intervall were presented. Two equally difficult versions of the task using different finger combinations were established in order to avoid carry over effects in performance. The finger movements were recorded with a three-dimensional ultrasound movement analysis system (Zebris).

All subjects had substantial gain in performance across the selfpaced blocks. Average increase in number of correct moves was 87% (from 27.8 to 51.9). There was no significant difference neither between the versions of the task nor between placebo vs. verum. Also, there was no significant difference between first and second session, indicating that there was no carry over effect in performance. ppTMS revealed no significant differences in cortical excitability between groups.

The newly developed skill acquisition task yields robust single subject 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 steady-state induced by repeated drug applications. This could explain why RBX did not modulate motor behavior.