Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex.

Abstract:  Brain dopamine is implicated in the regulation of movement, attention, reward and learning. Dysfunction of dopamine plays a role in Parkinson's disease, schizophrenia and drug addiction. It is released in the striatum when dopamine neurons in the midbrain undergo burst firing. Several animal studies have shown that dopamine can also be released under direct control of glutamatergic corticostriatal efferents. However, the existence and physiological significance of this mode of action remain controversial. We have shown previously that repetitive transcranial magnetic stimulation (rTMS) of the human prefrontal cortex led to focal dopamine release in the ipsilateral caudate nucleus, supporting the corticostriatal mode of dopamine release. Using the same experimental approach, we sought to confirm this hypothesis. We used [11C]raclopride and PET to measure changes in extracellular dopamine concentration following rTMS of the motor cortex in six healthy human subjects. rTMS of the left primary motor cortex caused a reduction in [11C]raclopride binding in the left putamen compared with rTMS of the left occipital cortex. There were no changes in binding in the right putamen, caudate nucleus or nucleus accumbens. The area of statistically significant change in binding corresponded closely to the known projection zone of corticostriatal efferents originating in monkey motor cortex. This finding has implications for the functional role of subcortical dopamine.