Noradrenergic modulation of human cortex excitability by the presynaptic alpha(2)-antagonist yohimbine

The objective of this study was to determine if yohimbine, a central norepinephrine enhancing drug, increases cortico-motoneuronal excitability in intact humans. Transcranial magnetic stimulation was used to assess excitability of the motor system reflected in the parameters motor threshold, recruitment curve, intracortical inhibition and intracortical facilitation before and after oral administration of 20 and 40 mg yohimbine. Oral intake of 40 but not 20 mg yohimbine increased slope and plateau of the recruitment curve and intracortical facilitation. Motor threshold and intracortical inhibition remained unchanged. The data show that pharmacological enhancement of central norepinephrine in humans is effective to increase the cortico-motoneuronal excitability. Since cortical excitability is closely linked to neuroplasticity, this observation might be of possible relevance for strategies to enhance rehabilitative processes after cortical lesions by pairing noradrenergic drugs with motor training.