Studies in humans show antidepressant potential for transcranial magnetic stimulation (TMS). We therefore studied TMS in animal models of depression and compared its effects with those of ECS. ECS in rats has several robust behavioral effects, including enhancement of apomorphine-induced stereotypy, reduction of immobility time in the Porsolt swim test, and increases in seizure threshold for subsequent stimulation. Seven or 10 days of daily TMS consistently enhanced apomorphine-induced stereotypy, whereas a single session of TMS did not. Two TMS treatments markedly reduced immobility in the Porsolt swim test, as does ECS. A single TMS treatment markedly reduces the percentage of rats seizing in response to a ECS-like electrical stimulus to the brain 10 s later, as does an ECS treatment itself but not a sub-convulsive electrical stimulus to the brain. Long-term administration of ECS as well as other antidepressant treatments downregulates beta-adrenergic receptors. We found that TMS significantly reduced the density of [3H]CGP-12177 (a radioligand with beta-adrenergic affinity) binding sites in cortical (p < 0.05) but not hippocampal membranes. The role of monoamines in the mechanism of action of antidepressant treatments was investigated in numerous studies. Region-specific changes in the brain steady-state levels, and turnover rates of monoamines were detected 10 s after administration of a single repetitive TMS (rTMS) session. In the striatum and hippocampus, dopamine levels were increased by 25 +/- 1.5% and 18 +/- 0.8%, respectively, but were reduced in frontal cortex and decreased in the striatum and hippocampus in the TMS-treated rats with no change to the midbrain. TMS caused an increase in serotonin and 5-HIAA levels in the hippocampus but not in other brain regions examined in this study. The ability of TMS to induce behavioral and biochemical alterations similar to those of ECS may further support the potential role of TMS as an antidepressant treatment and bring us closer to the understanding of the mechanism of action of TMS.