Intracortical excitability is modulated by a norepinephrine-reuptake inhibitor as measured with paired-pulse transcranial magnetic stimulation

Objective: Paired-pulse transcranial magnetic stimulation (ppTMS) of the motor cortex can be used to measure intracortical inhibition and facilitation of evoked motor potentials dependent on different interstimulus intervals (ISI). The reuptake-inhibition of norepinephrine, known as an excitatory neuromodulator and neurotransmitter, was postulated to enhance cortical excitability through increased facilitation and reduced inhibition as measured with ppTMS. Methods: Eight healthy subjects were examined with ppTMS at ISIs of 2, 3, 4, 5, 6, 7, 8, 10, 15 and 20 ms before and approximately 1.5 h after ingestion of 8 mg reboxetine. The group effects at the different ISIS pre/post reboxetine intake were analysed. Results: Post-reboxetine ppTMS showed an enhanced intracortical facilitation effect at ISIs of 8, 10, 15 and 20 ms. A decreased inhibition was found at an ISI of 3 ms. Conclusions: Reboxetine-induced higher postsynaptic norepinephrine level enhances intracortical excitability as measured with ppTMS. This finding provides new perspectives for evaluating neurophysiological properties of antidepressive medication and for investigating the pathophysiology of depression.