title: Intracortical excitability is modulated by a norepinephrine-reuptake inhibitor as measured with paired-pulse transcranial magnetic stimulation.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of Ulm, Leimgrubenweg 12, 89070 Ulm, Germany. uwe.herwig@medizin.uni-ulm.de
authors.forename: Uwe
authors.initials: U
authors.lastname: Herwig
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bräuer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Connemann
authors.forename: Manfred
authors.initials: M
authors.lastname: Spitzer
authors.forename: Carlos
authors.initials: C
authors.lastname: Schönfeldt-Lecuona
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004574:Electromagnetic Fields; D005071:Evoked Potentials; D005260:Female; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009044:Motor Cortex / Q000187:drug effects* / Q000502:physiology; D000077593:Reboxetine; D013997:Time Factors
chemical_list: D018759:Adrenergic Uptake Inhibitors; D009025:Morpholines; D000077593:Reboxetine