- Transcranial magnetic stimulation (TMS) is a non-invasive approach used for stimulating the human brain. Repetitive stimulation over the prefrontal cortex has proven effective in the treatment of major depression, however the mechanism of the antidepressant action is unknown. Since the nucleus accumbens is a major region implicated in reward circuitry and depressive disorders, we used the microdialysis technique to study some of the neurochemical changes induced in that region during and after acute TMS. Magnetic stimulation was applied over the frontal or the caudal cortex of the rat brain using a special coil design and microdialysis samples were collected before, during and after the stimulation session. The extracellular levels of both dopamine and glutamate in the nucleus accumbens were increased during the stimulation while the extracellular levels of acetylcholine were not affected. Stimulation over the caudal cortex caused a greater increase in dopamine levels than the stimulation over the frontal cortex, while such difference was not observed for glutamate levels. The changes in dopamine and glutamate extracellular levels in the nucleus accumbens may play a role in the antidepressant effect of TMS and it is therefore suggested that the effect of stimulation over caudal cortical sites on depressive patients will be examined.